IOS Press
Acta Medica Okayama
1387-2877
96
2
2023
Protective Effects of Rivaroxaban on White Matter Integrity and Remyelination in a Mouse Model of Alzheimer’s Disease Combined with Cerebral Hypoperfusion
609
622
EN
Zhihong
Bian
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Xinran
Hu
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Xia
Liu
Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Haibo
Yu
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yuting
Bian
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Hongming
Sun
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yusuke
Fukui
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Ryuta
Morihara
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Hiroyuki
Ishiura
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Toru
Yamashita
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Background:Alzheimer’s disease (AD) is characterized by cognitive dysfunction and memory loss that is accompanied by pathological changes to white matter. Some clinical and animal research revealed that AD combined with chronic cerebral hypoperfusion (CCH) exacerbates AD progression by inducing blood-brain barrier dysfunction and fibrinogen deposition. Rivaroxaban, an anticoagulant, has been shown to reduce the rates of dementia in atrial fibrillation patients, but its effects on white matter and the underlying mechanisms are unclear. <br>
Objective:The main purpose of this study was to explore the therapeutic effect of rivaroxaban on the white matter of AD+CCH mice. <br>
Methods:In this study, the therapeutic effects of rivaroxaban on white matter in a mouse AD+CCH model were investigated to explore the potential mechanisms involving fibrinogen deposition, inflammation, and oxidative stress on remyelination in white matter. <br>
Results:The results indicate that rivaroxaban significantly attenuated fibrinogen deposition, fibrinogen-related microglia activation, oxidative stress, and enhanced demyelination in AD+CCH mice, leading to improved white matter integrity, reduced axonal damage, and restored myelin loss.<br> Conclusions:These findings suggest that long-term administration of rivaroxaban might reduce the risk of dementia.
No potential conflict of interest relevant to this article was reported.
SAGE Publications
Acta Medica Okayama
0963-6897
32
2023
Safety and Clinical Effects of a Muse Cell-Based Product in Patients With Amyotrophic Lateral Sclerosis: Results of a Phase 2 Clinical Trial
EN
Toru
Yamashita
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yumiko
Nakano
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ryo
Sasaki
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Koh
Tadokoro
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yoshio
Omote
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Taijun
Yunoki
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yuko
Kawahara
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Namiko
Matsumoto
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yuki
Taira
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Chika
Matsuoka
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ryuta
Morihara
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Koji
Abe
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of motor neurons. Multilineage-differentiating stress-enduring (Muse) cells are unique endogenous stem cells that show therapeutic effects on motor function in ALS mouse models. We conducted a single-center open phase II clinical trial to evaluate the safety and clinical effects of repeated intravenous injections of an allogenic Muse cell-based product, CL2020, in patients with ALS. Five patients with ALS received CL2020 intravenously once a month for a total of six doses. The primary endpoints were safety and tolerability, and the secondary endpoint was the rate of change in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score. In addition, serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), sphingosine-1-phosphate (S1P), cerebrospinal fluid chitotriosidase-1 (CHIT-1), and neurofilament light chain (NfL) levels were evaluated. The CL2020 treatment was highly tolerated without serious side effects. The ALSFRS-R score change trended upward at 12 months post-CL2020 treatment compared with that at 3 months pre-administration, but the difference was not statistically significant. Among five patients diagnosed with ALS, three exhibited a decrease in the rate of ALSFRS-R score change, one demonstrated an increase, and another showed no change. In addition, the patients’ serum IL-6 and TNF-α levels and cerebrospinal fluid CHIT-1 and NfL levels increased for up to 6 months post-treatment; however, their serum S1P levels continuously decreased over 12 months. These findings indicate a favorable safety profile of CL2020 therapy. In the near future, a double-blind study of a larger number of ALS patients should be conducted to confirm the efficacy of ALS treatment with CL2020.
No potential conflict of interest relevant to this article was reported.
Elsevier BV
Acta Medica Okayama
0006-8993
1821
2023
Injection of exogenous amyloid-β oligomers aggravated cognitive deficits, and activated necroptosis, in APP23 transgenic mice
148565
EN
Haibo
Yu
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ryuta
Morihara
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ricardo
Ota-Elliott
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Zhihong
Bian
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yuting
Bian
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Xinran
Hu
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Hongming
Sun
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yusuke
Fukui
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Koji
Abe
National Center Hospital, National Center of Neurology and Psychiatry
Hiroyuki
Ishiura
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Toru
Yamashita
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by the loss of synapses and neurons in the brain, and the accumulation of amyloid plaques. Aβ oligomers (AβO) play a critical role in the pathogenesis of AD. Although there is increasing evidence to support the involvement of necroptosis in the pathogenesis of AD, the exact mechanism remains elusive. In the present study, we explored the effect of exogenous AβO injection on cell necroptosis and cognitive deficits in APP23 transgenic mice. We found that intrahippocampal injection of AβO accelerated the development of AD pathology and caused cognitive impairment in APP23 mice. Specifically, AβO injection significantly accelerated the accumulation of AβO and increased the expression level of phosphorylated-tau, and also induced necroptosis. Behavioral tests showed that AβO injection was associated with cognitive impairment. Furthermore, necroptosis induced by AβO injection occurred predominantly in microglia of the AD brain. We speculate that AβO increased necroptosis by activating microglia, resulting in cognitive deficits. Our results may aid in an understanding of the role played by AβO in AD from an alternative perspective and provide new ideas and evidence for necroptosis as a potential intervention and therapeutic target for AD.
No potential conflict of interest relevant to this article was reported.
SAGE Publications
Acta Medica Okayama
0963-6897
32
2023
Human Cord Blood-Endothelial Progenitor Cells Alleviate Intimal Hyperplasia of Arterial Damage in a Rat Stroke Model
EN
Hongming
Sun
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Ryuta
Morihara
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Tian
Feng
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Zhihong
Bian
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Haibo
Yu
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Xiao
Hu
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Xinran
Hu
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yuting
Bian
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Ryo
Sasaki
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yusuke
Fukui
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mami
Takemoto
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Taijun
Yunoki
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yumiko
Nakano
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Koji
Abe
National Center Hospital, National Center of Neurology and Psychiatry
Toru
Yamashita
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Human cord blood-endothelial progenitor cells (hCB-EPCs) isolated from the human umbilical cord can be used to repair damaged arteries. In this study, we used an animal model with pathological changes that mimics artery wall damage caused by stent retrievers in humans. We injected hCB-EPCs to investigate their effect on endothelial hyperplasia and dysfunction during intimal repair. Four groups were established based on the length of reperfusion (3 and 28 days), as well as the presence or absence of hCB-EPC therapy. Damage to the internal carotid artery was evaluated by hematoxylin-eosin and immunohistochemical staining. Stroke volume was not significantly different between non-EPC and EPC groups although EPC treatment alleviated intimal hyperplasia 28 days after intimal damage. Vascular endothelial growth factor (VEGF) and eNOS expression were significantly higher in the EPC-treated group than in the non-EPC group 3 days after intimal damage. In addition, MMP9 and 4HNE expression in the EPC-treated group was significantly lower than in the non-EPC group. Ultimately, this study found that venous transplantation of hCB-EPCs could inhibit neointimal hyperplasia, alleviate endothelial dysfunction, suppress intimal inflammation, and reduce oxidative stress during healing of intimal damage.
No potential conflict of interest relevant to this article was reported.
岡山医学会
Acta Medica Okayama
0030-1558
135
1
2023
神経軸索スフェロイド形成を伴う遺伝性びまん性白質脳症について
34
35
EN
Taijun
Yunoki
Department of Neurology, Okayama University Hospital
Toru
Yamashita
Department of Neurology, Okayama University Hospital
No potential conflict of interest relevant to this article was reported.
Elsevier BV
Acta Medica Okayama
0022-510X
447
2023
Neuroprotective effects of carnosine in a mice stroke model concerning oxidative stress and inflammatory response
120608
EN
Xinran
Hu
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yusuke
Fukui
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Tian
Feng
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Zhihong
Bian
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Haibo
Yu
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Ryuta
Morihara
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Xiao
Hu
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yuting
Bian
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Hongming
Sun
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mami
Takemoto
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yumiko
Nakano
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Taijun
Yunoki
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Koji
Abe
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Toru
Yamashita
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Carnosine (β-alanyl-L-histidine) is a natural dipeptide with multiple neuroprotective properties. Previous studies have advertised that carnosine scavenges free radicals and displays anti-inflammatory activity. However, the underlying mechanism and the efficacies of its pleiotropic effect on prevention remained obscure. In this study, we aimed to investigate the anti-oxidative, anti-inflammative, and anti-pyroptotic effects of carnosine in the transient middle cerebral artery occlusion (tMCAO) mouse model. After a daily pre-treatment of saline or carnosine (1000 mg / kg / day) for 14 days, mice (n = 24) were subjected to tMCAO for 60 min and continuously treated with saline or carnosine for additional 1 and 5 days after reperfusion. The administration of carnosine significantly decreased infarct volume 5 days after the tMCAO (*p < 0.05) and effectively suppressed the expression of 4-HNE, 8-OHdG, Nitrotyrosine 5 days, and RAGE 5 days after tMCAO. Moreover, the expression of IL-1β was also significantly suppressed 5 days after tMCAO. Our present findings demonstrated that carnosine effectively relieves oxidative stress caused by ischemic stroke and significantly attenuates neuroinflammatory responses related to IL-1β, suggesting that carnosine can be a promising therapeutic strategy for ischemic stroke.
No potential conflict of interest relevant to this article was reported.
CUREUS INC
Acta Medica Okayama
2168-8184
15
3
2023
A Case of Drug-Resistant Myoclonus Improved by Only Slight Adjustment to the Hemodialysis Setting
e36104
EN
Ryo
Sasaki
Department of Neurology, Okayama University
Chika
Matsuoka
Department of Neurology, Hiroshima City Hiroshima Citizens Hospital
Toru
Yamashita
Department of Neurology, Okayama University
Masaru
Kinomura
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University
Koji
Abe
Department of Neurology, National Center of Neurology and Psychiatry
Myoclonus, a rare complication in patients with end-stage renal disease, is typically ameliorated through hemodialysis. The present case concerns an 84-year-old male with chronic renal failure undergoing hemodialysis, presenting involuntary movements in his limbs, which gradually worsened from the initiation of hemodialysis without constant elevation of serum blood urea nitrogen and electrolytes levels. Surface electromyography revealed characteristic findings consistent with myoclonus. He was diagnosed with subcortical-nonsegmental myoclonus related to hemodialysis, and the myoclonus was significantly alleviated after slightly increasing the post-dialysis target weight even though drug treatment was ineffective. This case suggests that drug-resistant myoclonus in patients with renal failure may be improved by adjusting hemodialysis settings, even in cases of atypical dialysis disequilibrium syndrome.
No potential conflict of interest relevant to this article was reported.
The Japanese Society of Internal Medicine
Acta Medica Okayama
0918-2918
62
3
2023
Actual Telemedicine Needs of Japanese Patients with Neurological Disorders in the COVID-19 Pandemic
365
371
EN
Ryo
Sasaki
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Taijun
Yunoki
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yumiko
Nakano
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yusuke
Fukui
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mami
Takemoto
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Ryuta
Morihara
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Koji
Abe
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Toru
Yamashita
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Objective During the coronavirus disease 2019 (COVID-19) pandemic, many social activities have moved online using applications for digital devices (e.g. computers, smartphones). We investigated the needs of telemedicine and trends in medical status and social care situations of Japanese patients with neurological disorders in order to estimate their affinity for an online telemedicine application. Methods We designed an original questionnaire for the present study that asked participants what problems they had with hospital visits, how the COVID-19 pandemic had affected their lives, and whether or not they would like to receive telemedicine.Patients The present study included volunteer caregivers, participants with Parkinson's disease (PD), epiamyotrophic lateral sclerosis (ALS), headache, myopathy, and other neurological diseases from Okayama University Hospital. Results A total of 29.6% of patients wanted to use telemedicine. Patients with ultheadaches (60.0%) and epilepsy (38.1%) were more likely to want to use telemedicine than patients with PD (17.8%) or stroke (19.0%). Almost 90% of patients had access to a digital device, and there was no association between favoring telemedicine, ownership of a digital device, hospital visiting time, or waiting time at the hospital, although age was associated with motivation to telemedicine use (52.6 vs. 62.2 years old, p < 0.001). Conclusion We can contribute to the management of the COVID-19 pandemic and the medical economy by promoting telemedicine, especially for young patients with headaches or epilepsy.
No potential conflict of interest relevant to this article was reported.
Wiley
Acta Medica Okayama
2049-4173
11
1
2022
Novel ABCD1 mutation detected in a symptomatic female carrier of adrenoleukodystrophy
58
60
EN
Yumiko
Nakano
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yuki
Taira
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ryo
Sasaki
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Koh
Tadokoro
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Taijun
Yunoki
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Emi
Nomura
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yusuke
Fukui
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Mami
Takemoto
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ryuta
Morihara
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Nobuyuki
Shimozawa
Division of Genomics Research, Life Science Research Center, Gifu university
Toru
Yamashita
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
X-linked adrenoleukodystrophy (ALD) is a major peroxisomal disorder, in which abnormal accumulation of very long-chain fatty acids (VLCFA) caused by ABCD1 gene mutation results in damage to the peripheral and central nervous system and adrenal gland. While affected male patients with ALD present severe neurological symptoms, some female carriers slowly develop spastic gait and urinary incontinence. We report a case of a symptomatic female ALD carrier with a novel ABCD1 gene mutation. She has developed progressive gait disturbance since age 40, and her father and sister had similar symptoms. When admitted to our hospital at age 66, blood analysis showed slight increase of VLCFA, and DNA analysis of ABCD1 gene revealed a novel heterozygous missense mutation (c.1700 A>C, p.Gln567Pro). The genetic testing for ABCD1 gene can be considered in female patients over middle age presenting spastic gait, because female ALD carriers tend to be symptomatic beyond age 60.
No potential conflict of interest relevant to this article was reported.
Wiley
Acta Medica Okayama
2049-4173
10
5
2022
Japanese case of Charcot–Marie–Tooth disease type 2Z with severe retinitis pigmentosa
266
268
EN
Emi
Nomura
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Koh
Tadokoro
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Ryo
Sasaki
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yumi
Nakata
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yumiko
Nakano
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Taijun
Yunoki
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mami
Takemoto
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Ryuta
Morihara
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Masahiro
Ando
Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University
Hiroshi
Takashima
Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University
Toru
Yamashita
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Charcot-Marie-Tooth disease type 2Z (CMT2Z) shows highly variable clinical features. We report the first Japanese CMT2Z patient with a c.754C>T (p.R252W) substitution of the MORC2 gene, complicating severe retinitis pigmentosa. The MORC2 mutants were involved in a decrease in cell survival through induction of apoptosis. Thus, the MORC2 mutation might be involved in the degeneration of photoreceptors and the development of retinitis pigmentosa.
No potential conflict of interest relevant to this article was reported.
Wiley
Acta Medica Okayama
2049-4173
10
5
2022
A Japanese case of successful surgical resection of cerebral cavernous malformations with a CCM2 mutation
255
258
EN
Emi
Nomura
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yoshio
Omote
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mami
Takemoto
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Nozomi
Hishikawa
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yumiko
Nakano
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Taijun
Yunoki
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Ryuta
Morihara
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Tatsuya
Sasaki
Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Hiroyuki
Akagawa
Tokyo Women's Medical University Institute for Integrated Medical Sciences
Koji
Abe
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Toru
Yamashita
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama University
Cerebral cavernous malformations (CCMs) are congenital abnormalities of cerebral vessels. Surgical resection is rarely considered for the control of epilepsy in a first seizure patient with vascular malformation. In contrast, lesions that produce repetitive or progressive symptoms should be considered for surgical resection as treatment. Herein, we report a Japanese patient with a CCM2 mutation, c.609G>A (p.K203K) substitution, who showed drug-resistant epilepsy and dramatic improvement after surgical resection.
No potential conflict of interest relevant to this article was reported.
IOS Press
Acta Medica Okayama
1387-2877
86
1
2022
Protective Effect of Rivaroxaban Against Amyloid Pathology and Neuroinflammation Through Inhibiting PAR-1 and PAR-2 in Alzheimer’s Disease Mice
111
123
EN
Zhihong
Bian
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Xia
Liu
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Tian
Feng
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Haibo
Yu
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Xiao
Hu
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Xinran
Hu
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yuting
Bian
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Hongming
Sun
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Koh
Tadokoro
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mami
Takemoto
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Taijun
Yunoki
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yumiko
Nakano
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yusuke
Fukui
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Ryuta
Morihara
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Koji
Abe
National Center Hospital, National Center of Neurology and Psychiatry
Toru
Yamashita
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Background: Recent studies have revealed that atrial fibrillation (AF) patients have a high risk of developing cognitive impairment, vascular dementia, and Alzheimer’s disease (AD). Some reports suggest that the application of oral anticoagulant with an appropriate dose may have a preventive effect on AD. However, which oral anticoagulant drug is more appropriate for preventing AD and the underlying mechanism(s) is still unknown. Objective: The aim of the present study was to assess the treatment effect of rivaroxaban administration as well as investigate the roles of PAR-1 and PAR-2 in the AD + CAA mice model. Methods: In the present study, we compared a traditional oral anticoagulant, warfarin, and a direct oral anticoagulant (DOAC), rivaroxaban, via long-term administration to an AD with cerebral amyloid angiopathy (CAA) mice model. Results: Rivaroxaban treatment attenuated neuroinflammation, blood-brain barrier dysfunction, memory deficits, and amyloid-β deposition through PAR-1/PAR-2 inhibition in the AD + CAA mice model compared with warfarin and no-treatment groups. Conclusion: The present study demonstrates that rivaroxaban can attenuate AD progress and can be a potential choice to prevent AD.
No potential conflict of interest relevant to this article was reported.
Elsevier BV
Acta Medica Okayama
0022-510X
353
1-2
2015
Selective disappearance of medial back muscles in a case of myotonic dystrophy type 1
185
186
EN
Ryuta
Morihara
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
Nozomi
Hishikawa
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
Toru
Yamashita
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
Kentaro
Deguchi
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
Tomoko
Kurata
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
Koji
Abe
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
Here, we report a unique case of late-onset myotonic dystrophy type 1 in a 64-year-old woman, with selective disappearance of the medial lower back muscles. We compared the clinical features of this patient with those of a cohort of 29 patients with myotonic dystrophy type 1 to clarify the correlation between clinical features and lower back muscle atrophy. After classification into three subgroups according to muscle atrophy pattern, medial muscle atrophy was present in 17.2% of the patients. Affected patients were older at onset than non-affected patients, and limb muscle power and respiratory function decreased with atrophy progression.
No potential conflict of interest relevant to this article was reported.
Elsevier BV
Acta Medica Okayama
0022-510X
387
15
2018
Familial and sporadic chronic progressive degenerative parietal ataxia
70
74
EN
Ryuta
Morihara
Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University
Toru
Yamashita
Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University
Kentaro
Deguchi
Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University
Tomoko
Kurata
Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University
Emi
Nomura
Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University
Kota
Sato
Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University
Yumiko
Nakano
Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University
Yasuyuki
Ohta
Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University
Nozomi
Hishikawa
Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University
Takeshi
Ikeuchi
Department of Molecular Genetics, Bioresource Science Branch, Center of Bioresource, Brain Research Institute Niigata University
Masataka
Kitaguchi
Department of Neurology, Baba Memorial Hospital
Koji
Abe
Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University
Background & objective: Parietal ataxia has been mainly reported as a consequence of acute ischemic stroke, while degenerative parietal ataxia has not been reported.
Methods: We investigated clinical characteristics, neuroimaging data, and genetic analysis of patients with cerebellar ataxia plus parietal atrophy.
Results: We identified seven patients, including five patients from two families, with chronic progressive cerebellar ataxia due to degenerative parietal atrophy but not stroke. Age at onset of ataxia was 57.6 +/- 6.9 years. All patients showed chronic progressive cerebellar ataxia with severity of ataxic gait > limb ataxia > dysarthria. Patients showed no cognitive dysfunction, muscle weakness, or parkinsonism, and only two patients showed mild sensory disturbances. The seven patients showed lateralized limb ataxia with greater contralateral parietal lobe atrophy by magnetic resonance imaging, and hypoperfusion by single photon emission computed tomography, without any abnormal cerebellar pathology (i.e., crossed cerebellar diaschisis). Pathogenic mutations in the microtubule-associated protein tau gene were not found using two single nucleotide polymorphisms.
Conclusions: This is the first description showing unique clinical features of familial and sporadic chronic progressive degenerative parietal ataxia.
No potential conflict of interest relevant to this article was reported.
Wiley
Acta Medica Okayama
0360-4012
95
9
2016
Reduction of intracerebral hemorrhage by rivaroxaban after tPA thrombolysis is associated with downregulation of PAR-1 and PAR-2
1818
1828
EN
Ryuta
Morihara
Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University
Toru
Yamashita
Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University
Syoichiro
Kono
Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University
Jingwei
Shang
Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University
Yumiko
Nakano
Departments of Neurology
Kota
Sato
Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University
Nozomi
Hishikawa
Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University
Yasuyuki
Ohta
Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University
Stefan
Heitmeier
Bayer Pharma AG, Drug Discovery - Global Therapeutic Research Groups, Cardiovascular Pharmacology
Elisabeth
Perzborn
Bayer Pharma AG, Drug Discovery - Global Therapeutic Research Groups, Cardiovascular Pharmacology
Koji
Abe
Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University
This study aimed to assess the risk of intracerebral hemorrhage (ICH) after tissue-type plasminogen activator (tPA) treatment in rivaroxaban compared with warfarin-pretreated male Wistar rat brain after ischemia in relation to activation profiles of protease-activated receptor-1, -2, -3, and -4 (PAR-1, -2, -3, and -4). After pretreatment with warfarin (0.2 mg/kg/day), low-dose rivaroxaban (60 mg/kg/day), high-dose rivaroxaban (120 mg/kg/day), or vehicle for 14 days, transient middle cerebral artery occlusion was induced for 90 min, followed by reperfusion with tPA (10 mg/kg/10 ml). Infarct volume, hemorrhagic volume, immunoglobulin G leakage, and blood parameters were examined. Twenty-four hours after reperfusion, immunohistochemistry for PARs was performed in brain sections. ICH volume was increased in the warfarin-pretreated group compared with the rivaroxaban-treated group. PAR-1, -2, -3, and -4 were widely expressed in the normal brain, and their levels were increased in the ischemic brain, especially in the peri-ischemic lesion. Warfarin pretreatment enhanced the expression of PAR-1 and PAR-2 in the peri-ischemic lesion, whereas rivaroxaban pretreatment did not. The present study shows a lower risk of brain hemorrhage in rivaroxaban-pretreated compared with warfarin-pretreated rats following tPA administration to the ischemic brain. It is suggested that the relative downregulation of PAR-1 and PAR-2 by rivaroxaban compared with warfarin pretreatment might be partly involved in the mechanism of reduced hemorrhagic complications in patients receiving rivaroxaban in clinical trials. © 2016 Wiley Periodicals, Inc.
No potential conflict of interest relevant to this article was reported.
SAGE Publications
Acta Medica Okayama
0271-678X
2022
Efficacy and safety of spot heating and ultrasound irradiation on in vitro and in vivo thrombolysis models
EN
Ryuta
Morihara
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Toru
Yamashita
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yosuke
Osakada
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Tian
Feng
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Xinran
Hu
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yusuke
Fukui
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
Koh
Tadokoro
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Mami
Takemoto
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Koji
Abe
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
<jats:p> The feasibility of transcranial sonothrombolysis has been demonstrated, although little is known about the relationships between thermal or mechanical mechanisms and thrombolytic outcomes. Therefore, the present study aims to reveal the effect and safety of temperature and ultrasound through in vitro and in vivo thrombolysis models. Artificial clots in microtubes were heated in a water bath or sonicated by ultrasound irradiation, and then clots weight decrease with rising temperature and sonication time was confirmed. In the in vitro thrombotic occlusion model, based on spot heating, clot volume was reduced and clots moved to the distal side, followed by recanalization of the occlusion. In the in vivo study, the common carotid artery of rats was exposed to a spot heater or to sonication. No brain infarct or brain blood barrier disruption was shown, but endothelial junctional dysintegrity and an inflammatory response in the carotid artery were detected. The present spot heating and ultrasound irradiation models seem to be effective for disintegrating clots in vitro, but the safety of the in vivo model was not fully supported by the data. However, the data indicates that a shorter time exposure could be less invasive than a longer exposure. </jats:p>
No potential conflict of interest relevant to this article was reported.
Japanese Society of Internal Medicine
Acta Medica Okayama
0918-2918
56
17
2017
Successful Delayed Aortic Surgery for a Patient with Ischemic Stroke Secondary to Aortic Dissection
2343
2346
EN
Ryuta
Morihara
Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University
Toru
Yamashita
Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University
Kentaro
Deguchi
Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan
Keiichiro
Tsunoda
Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan
Yasuhiro
Manabe
Department of Neurology, Okayama National Hospital Medical Center, Japan
Yoshiaki
Takahashi
Department of Neurology, Okayama National Hospital Medical Center, Japan
Taijun
Yunoki
Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan
Kota
Sato
Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan
Yumiko
Nakano
Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan
Syoichiro
Kono
Department of Neurology, Okayama National Hospital Medical Center, Japan
Yasuyuki
Ohta
Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan
Nozomi
Hishikawa
Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan
Koji
Abe
Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan
The diagnosis of aortic dissection (AD) is sometimes difficult within the limited time window of recombinant tissue plasminogen activator (tPA) for ischemic stroke (IS). A 60-year-old man developed sudden left hemiparesis due to IS. During tPA infusion, his blood pressure dropped and consciousness declined. After transfer to our hospital, carotid duplex ultrasonography led to a diagnosis of AD. Emergency surgery was postponed because of the risk of hemorrhagic transformation. The patient successfully underwent aortic surgery on day 5 and was discharged with a remarkable improvement in his symptoms. Delayed surgery may avoid hemorrhagic transformation in patients with AD-induced IS who have received tPA.
No potential conflict of interest relevant to this article was reported.
Wiley
Acta Medica Okayama
2049-4173
10
2022
A case of a heterozygous ABCC6 mutation showing recurrent ischemic strokes and intracranial hemorrhages
98
101
EN
Emi
Nomura
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yuko
Kawahara
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yoshio
Omote
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yoshiaki
Takahashi
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Namiko
Matsumoto
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Ken
Ikegami
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mami
Takemoto
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Nozomi
Hishikawa
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yumiko
Nakano
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Taijun
Yunoki
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Ryuta
Morihara
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Masahiro
Uemura
Department of Neurology, Brain Research Institute, Niigata University
Koji
Abe
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Toru
Yamashita
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mutations in the ATP-binding cassette subfamily C member 6 (ABCC6) gene are responsible for pseudoxanthoma elasticum (PXE). PXE is a rare genetic metabolic disease with autosomal recessive inheritance that shows ectopic mineralization in skin, eyes and blood vessels, and causes cerebrovascular disease. There are few reports of intracranial hemorrhages in patients with the ABCC6 mutation. We report the first Japanese case with a heterozygous ABCC6 mutation displaying recurrent ischemic strokes and intracranial hemorrhages. We propose that the ABCC6 mutation may be one cause of neurovascular diseases with a family history.
No potential conflict of interest relevant to this article was reported.
Japanese Society of Internal Medicine
Acta Medica Okayama
0918-2918
58
21
2019
Spastic Paraplegia Accompanied by Extrapyramidal Sign and Frontal Cognitive Dysfunction
3163
3165
EN
Ryo
Sasaki
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yasuyuki
Ohta
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kota
Sato
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Koh
Tadokoro
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yoshiaki
Takahashi
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Jingwei
Shang
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mami
Takemoto
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Nozomi
Hishikawa
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Toru
Yamashita
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Hiroyuki
Ishiura
Department of Neurology, The University of Tokyo Hospital
Shoji
Tsuji
Department of Molecular Neurology, The University of Tokyo Hospital, Japan Institute of Medical Genomics, International University of Health and Welfare
Koji
Abe
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
A complicated form of spastic paraplegia is a neurodegenerative disorder presenting as progressive spasticity in the bilateral lower limbs accompanied by some clinical features. The present case showed spastic paralysis and hyperreflexia in all extremities as well as lead pipe rigidity in the neck and bilateral upper extremities (R < L), decreased scores on frontal cognitive tests, a decreased accumulation of the right dorsal putamen on a DAT scan, and hypoperfusion of the bilateral frontal lobes on 99mTc-ECD single photon emission computed tomography (SPECT). The present case provides a new spectrum of spastic paraplegia based on the evidence of clinical scores and the findings of brain functional imaging.
No potential conflict of interest relevant to this article was reported.
Japanese Society of Internal Medicine
Acta Medica Okayama
0918-2918
58
7
2019
Characteristic Clinical Features of Werner Syndrome with a Novel Compound Heterozygous WRN Mutation c.1720+1G>A Plus c.3139-1G>C
1033
1036
EN
Namiko
Matsumoto
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yasuyuki
Ohta
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kentaro
Deguchi
Department of Neurology, Okayama Citizen's Hospital
Masayuki
Kishida
Department of General Internal Medicine, Okayama Citizen's Hospital
Kota
Sato
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Jingwei
Shang
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mami
Takemoto
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Nozomi
Hishikawa
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Toru
Yamashita
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Aki
Watanabe
Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University
Koutaro
Yokote
Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University
Minoru
Takemoto
Department of Diabetes, Metabolism and Endocrinology, School of Medicine, International University of Health and Welfare
Junko
Oshima
Department of Pathology, University of Washington
Koji
Abe
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Werner syndrome (WS) is an autosomal recessive progeroid disorder caused by mutations in the WRN gene (WRN). Most Japanese WS patients are born from a consanguineous marriage with homozygous WRN mutations. We herein report a rare WS patient born from non-consanguineous parents with compound heterozygous WRN mutations with a novel heterogeneous c.1720+1G>A substitution plus the most frequent heterogeneous c.3139-1G>C substitution among Japanese. Although the present case showed clinical characteristics common to previous Japanese WS patients, he had not developed any malignant tumors as of 43 years of age, suggesting that WS patients with this particular genetic mutation have a different phenotype than others.
No potential conflict of interest relevant to this article was reported.
Japanese Society of Internal Medicine
Acta Medica Okayama
0918-2918
58
3
2019
A Rare Case of Klinefelter Syndrome Accompanied by Spastic Paraplegia and Peripheral Neuropathy
437
440
EN
Ryo
Sasaki
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yasuyuki
Ohta
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yoshiaki
Takahashi
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Keiichiro
Tsunoda
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Koh
Tadokoro
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kota
Sato
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Jingwei
Shang
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mami
Takemoto
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Nozomi
Hishikawa
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Toru
Yamashita
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Koji
Abe
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Klinefelter syndrome is a chromosomal disorder with a typical karyotype of 47, XXY, accompanied by various neurological symptoms. We herein report the first case of Klinefelter syndrome with a rare mosaic form of 47, XXY and 48, XXXY, combined with both spastic paraplegia and peripheral motor neuropathy. This case showed spasticity and hyperreflexia with pathological reflexes and ankle clonus as well as muscle weakness in all extremities. A motor nerve conduction study and the magnetic motor evoked potential suggested motor axonal neuropathy and corticospinal tract disorders. The present case suggests that Klinefelter syndrome can present with both upper and lower motor neuron degeneration.
No potential conflict of interest relevant to this article was reported.
Japanese Society of Internal Medicine
Acta Medica Okayama
0918-2918
58
8
2019
Improving Anxiety in Subacute Myelo-optico-neuropathy (SMON) after an Automated Telephone Call Service
1081
1085
EN
Yasuyuki
Ohta
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Nozomi
Hishikawa
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kota
Sato
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mami
Takemoto
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Toru
Yamashita
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Shinji
Doutare
Doutare Medical Clinic
Koji
Abe
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Objective We evaluated the clinical effects of a telephone call service for psychological symptoms such as anxiety, depression or apathy in subacute myelo-optico-neuropathy (SMON) patients living alone or with a single caregiver. </br>
Methods Up to 16 SMON patients (4 men, 12 women) and 32 control subjects were evaluated by the geriatric depression scale (GDS), apathy scale (AS) and state and trait anxiety inventory (STAI) forms X-I, including the P and A values for depression, apathy and state anxiety including disturbed peace of mind and enhanced anxiety, respectively, before (pre) and three months after (post) the telephone call service. </br>
Results The SMON patients, especially women, had significantly worse baseline scores in GDS (depression), AS (apathy) and STAI (state anxiety) than control subjects. The automated telephone call service significantly improved the high baseline STAI scores, including the P and A scores (disturbed peace of mind and enhanced anxiety), of SMON patients but not the GDS or AS scores. </br>
Conclusion SMON patients, especially women, living alone or with a single caregiver showed higher baseline depression, apathy and anxiety scores than the control subjects. The present automated telephone call service proved to be a useful care tool for improving the anxiety of SMON patients with high STAI P and A scores.
No potential conflict of interest relevant to this article was reported.
The Japanese Society of Internal Medicine
Acta Medica Okayama
0918-2918
60
2
2021
The Oldest Japanese Case of Combined Central and Peripheral Demyelination, which Developed Nine Years After the First Instance of Optic Neuritis
305
308
EN
Emi
Nomura
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yuko
Kawahara
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yoshio
Omote
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Koh
Tadokoro
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mami
Takemoto
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Nozomi
Hishikawa
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Toru
Yamashita
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Hidenori
Ogata
Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University
Koji
Abe
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Combined central and peripheral demyelination (CCPD) causes demyelination in both the central and peripheral nervous systems. Anti-neurofascin 155 antibody plays an important pathogenic role in CCPD, but evidence concerning an association between this antibody and CCPD remains inconclusive. Although there have been no reports of precedent optic neuritis developing into CCPD, we herein report a Japanese man in whom optic neuritis recurred four times over nine years and who developed CCPD without positive antineurofascin 155 antibody. This case suggests the possibility of developing CCPD after optic nerve neuritis and the existence of an unknown antibody that induces CCPD.
No potential conflict of interest relevant to this article was reported.
BMC
Acta Medica Okayama
1477-7827
19
1
2021
Effect of edaravone on pregnant mice and their developing fetuses subjected to placental ischemia
19
EN
Marwa
Atallah
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Toru
Yamashita
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Koji
Abe
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Growing evidence indicates that reduced uterine perfusion pressure (RUPP) triggers the cascade of events leading to preeclampsia. Edaravone is a powerful free radical scavenger used for the treatment of ischemia/reperfusion diseases due to its anti-oxidative stress and anti-inflammatory properties. Here we investigate the effect of edaravone (3 mg/kg) on different maternal and fetal outcomes of RUPP-induced placental ischemia mice model. RUPP surgery was performed on gestation day (GD) 13 followed by edaravone injection from GD14 to GD18, sacrifice day. The results showed that edaravone injection significantly decreased the maternal blood pressure (113.2 +/- 2.3 mmHg) compared with RUPP group (131.5 +/- 1.9 mmHg). Edaravone increased fetal survival rate (75.4%) compared with RUPP group (54.4%), increased fetal length, weights, and feto-placental ratio (7.2 and 5.7 for RUPP and RUPP-Edaravone groups, respectively) compared with RUPP group. In addition, RUPP resulted in many fetal morphological abnormalities as well as severe delayed ossification, however edaravone decreased the morphological abnormalities and increased the ossification of the fetal endoskeleton. Edaravone improved the histopathological structure of the maternal kidney and heart as well as decreased the elevated blood urea and creatinine levels (31.5 +/- 0.15 mg/dl (RUPP), 25.6 +/- 0.1 mg/dl (RUPP+edaravone) for urea and 5.4 +/- 0.1 mg/dl (RUPP), 3.5 +/- 0.1 mg/dl (RUPP+edaravone) for creatinine) and decreased cleaved caspase-3 expression in the maternal kidney. In conclusion, this study demonstrated that our RUPP mice model recapitulated preeclampsia symptoms and edaravone injection ameliorated most of these abnormalities suggesting its effectiveness and potential application in preeclampsia treatment regimes.
No potential conflict of interest relevant to this article was reported.
Wiley
Acta Medica Okayama
2049-4173
9
2
2020
A new telestroke network system in northern area of Okayama prefecture
166
170
EN
Ryo
Sasaki
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Toru
Yamashita
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yoshio
Omote
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mami
Takemoto
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Nozomi
Hishikawa
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Taijun
Yunoki
Department of Neurology, Tsuyama Central Hospital
Kazuki
Kobayashi
Department of Neurosurgery, Tsuyama Central Hospital
Takashi
Sawata
Department of Gastrointestinal Surgery, Tsuyama 1st Hospital
Yuki
Sato
Department of Internal Medicine, Sato Memorial Hospital
Junichi
Kubota
Department of Internal Medicine, Tajiri Hospital
Masayuki
Mizobuchi
Department of Neurosurgery, Kaneda Hospital
Takashi
Hayashi
Department of Orthopedics, Sayo Central Hospital
Koji
Abe
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Background</br>
Telestroke network can provide rapid access to specialized treatment and improves on‐site management of acute stroke patients through the “hub‐and‐spoke” model. In the northern part of Okayama Prefecture, there has been a regional gap of stroke care due to the shortage of stroke specialists and facilities. In addition, due to the novel coronavirus disease 2019 (COVID‐19), it is required to reduce the unnecessary contact with stroke patients from other hospitals.</br>
Aim</br>
We organized a novel cost‐free telestroke network with an image and video sharing for neurological diseases in the northern part of Okayama Prefecture to improve the stroke management in the area.</br>
Method</br>
We prepared the tablet device on which Skype® application was installed for each hospital and recruited the patients who visited or hospitalized in the spoke hospitals and were suspected to have some neurological diseases from April 2019 to May 2020. The patient's clinical data were recorded and analyzed. </br>
Results</br>
During the study period, 5 patients were recruited including the cases with the initial diagnosis of stroke or brain tumor. Among them, 2 cases were transferred to the hub hospital, 2 cases were transferred to other hospitals, and 1 case was treated on site under specialist's advice.</br>
Conclusion</br>
The new telestroke network system may be beneficial for acute stroke management and reducing the unnecessary patient's transfer in the rural area, especially under coexistence with COVID‐19.
No potential conflict of interest relevant to this article was reported.
IOP Press
Acta Medica Okayama
1387-2877
73
1
2020
A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer’s Disease by Peptidome Technology
217
227
EN
Koji
Abe
Department of Neurology, Okayama University
Jingwei
Shang
Department of Neurology, Okayama University
Xiaowen
Shi
Department of Neurology, Okayama University
Toru
Yamashita
Department of Neurology, Okayama University
Nozomi
Hishikawa
Department of Neurology, Okayama University
Mami
Takemoto
Department of Neurology, Okayama University
Ryuta
Morihara
Department of Neurology, Okayama University
Yumiko
Nakano
Department of Neurology, Okayama University
Yasuyuki
Ohta
Department of Neurology, Okayama University
Kentaro
Deguchi
Department of Neurology, Okayama City Hospital, Okayama
Masaki
Ikeda
Department of Neurology, Gunma University, Graduate School of Medicine
Yoshio
Ikeda
Department of Neurology, Gunma University, Graduate School of Medicine
Koichi
Okamoto
Department of Neurology, Geriatrics Research Institute and Hospital
Mikio
Shoji
Department of Neurology, Geriatrics Research Institute and Hospital
Masamitsu
Takatama
Department of Neurology, Geriatrics Research Institute and Hospital
Motohisa
Kojo
Department of Neurology, Ako Chuo Hospital
Takeshi
Kuroda
Division of Neurology, Department of Medicine, Showa University, School of Medicine
Kenjiro
Ono
Division of Neurology, Department of Medicine, Showa University, School of Medicine
Noriyuki
Kimura
Department of Neurology, Faculty of Medicine, Oita University
Etsuro
Matsubara
Department of Neurology, Faculty of Medicine, Oita University
Yosuke
Osakada
Department of Neurology, Kurashiki Heisei Hospital
Yosuke
Wakutani
Department of Neurology, Kurashiki Heisei Hospital
Yoshiki
Takao
Department of Neurology, Kurashiki Heisei Hospital
Yasuto
Higashi
Department of Neurology, Himeji Central Hospital
Kyoichi
Asada
Membrane Protein and Ligand Analysis Center, Protosera Inc.,
Takehito
Senga
Membrane Protein and Ligand Analysis Center, Protosera Inc.,
Lyang-Ja
Lee
Membrane Protein and Ligand Analysis Center, Protosera Inc.,
Kenji
Tanaka
Membrane Protein and Ligand Analysis Center, Protosera Inc.,
Background:</br>
Because dementia is an emerging problem in the world, biochemical markers of cerebrospinal fluid (CSF) and radio-isotopic analyses are helpful for diagnosing Alzheimer’s disease (AD). Although blood sample is more feasible and plausible than CSF or radiological biomarkers for screening potential AD, measurements of serum amyloid- β (Aβ), plasma tau, and serum antibodies for Aβ1 - 42 are not yet well established.</br>
Objective:</br>
We aimed to identify a new serum biomarker to detect mild cognitive impairment (MCI) and AD in comparison to cognitively healthy control by a new peptidome technology.</br>
Methods:</br>
With only 1.5μl of serum, we examined a new target plate “BLOTCHIP®” plus a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) to discriminate control (n = 100), MCI (n = 60), and AD (n = 99). In some subjects, cognitive Mini-Mental State Examination (MMSE) were compared to positron emission tomography (PET) with Pittsburgh compound B (PiB) and the serum probability of dementia (SPD). The mother proteins of candidate serum peptides were examined in autopsied AD brains.</br>
Results:</br>
Apart from Aβ or tau, the present study discovered a new diagnostic 4-peptides-set biomarker for discriminating control, MCI, and AD with 87% of sensitivity and 65% of specificity between control and AD (***p < 0.001). MMSE score was well correlated to brain Aβ deposition and to SPD of AD. The mother proteins of the four peptides were upregulated for coagulation, complement, and plasticity (three proteins), and was downregulated for anti-inflammation (one protein) in AD brains.</br>
Conclusion:</br>
The present serum biomarker set provides a new, rapid, non-invasive, highly quantitative and low-cost clinical application for dementia screening, and also suggests an alternative pathomechanism of AD for neuroinflammation and neurovascular unit damage.
No potential conflict of interest relevant to this article was reported.
Nature Research
Acta Medica Okayama
2045-2322
10
1
2020
Therapeutic benefit of Muse cells in a mouse model of amyotrophic lateral sclerosis
17102
EN
Toru
Yamashita
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yoshihiro
Kushida
Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine
Shohei
Wakao
Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine
Koh
Tadokoro
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Emi
Nomura
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yoshio
Omote
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Mami
Takemoto
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Nozomi
Hishikawa
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yasuyuki
Ohta
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Mari
Dezawa
Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine
Koji
Abe
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss. Muse cells are endogenous reparative pluripotent-like stem cells distributed in various tissues. They can selectively home to damaged sites after intravenous injection by sensing sphingosine-1-phosphate produced by damaged cells, then exert pleiotropic effects, including tissue protection and spontaneous differentiation into tissue-constituent cells. In G93A-transgenic ALS mice, intravenous injection of 5.0x10(4) cells revealed successful homing of human-Muse cells to the lumbar spinal cords, mainly at the pia-mater and underneath white matter, and exhibited glia-like morphology and GFAP expression. In contrast, such homing or differentiation were not recognized in human mesenchymal stem cells but were instead distributed mainly in the lung. Relative to the vehicle groups, the Muse group significantly improved scores in the rotarod, hanging-wire and muscle strength of lower limbs, recovered the number of motor neurons, and alleviated denervation and myofiber atrophy in lower limb muscles. These results suggest that Muse cells homed in a lesion site-dependent manner and protected the spinal cord against motor neuron death. Muse cells might also be a promising cell source for the treatment of ALS patients.
No potential conflict of interest relevant to this article was reported.
BMC
Acta Medica Okayama
1471-2466
20
1
2020
Recovery from hypoxemia and Hypercapnia following noninvasive pressure support ventilation in a patient with statin-associated necrotizing myopathy: a case report
156
EN
Yuriko
Yamamura
Department of Nephrology, Rheumatology, Endocrinology and Metabolism Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yoshinori
Matsumoto
Department of Nephrology, Rheumatology, Endocrinology and Metabolism Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Koh
Tadokoro
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yasuyuki
Ohta
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kota
Sato
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Toru
Yamashita
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Masahiro
Yamamura
Center for Rheumatology, Okayama Saiseikai General Hospital
Ken-Ei
Sada
Department of Nephrology, Rheumatology, Endocrinology and Metabolism Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Koji
Abe
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Jun
Wada
Department of Nephrology, Rheumatology, Endocrinology and Metabolism Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Background: Statin-associated necrotizing myopathy (SANM) is a rare autoimmune disorder caused by administration of statins. SANM is characterized by weakness due to necrosis and regeneration of myofibers. Here we report the first case of SANM with acute respiratory failure treated with noninvasive pressure support ventilation in addition to immunosuppressants. <br/>
Case presentation: A 59-year-old woman who had been treated with 2.5 mg/day of rosuvastatin calcium for 5 years stopped taking the drug 4 months before admission to our hospital due to elevation of creatine kinase (CK). Withdrawal of rosuvastatin for 1 month did not decrease the level of CK, and she was admitted to our hospital due to the development of muscle weakness of her neck and bilateral upper extremities. Anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibodies were positive. Magnetic resonance imaging showed myositis, and muscle biopsy from the right biceps brachii muscle showed muscle fiber necrosis and regeneration without inflammatory cell infiltration, suggesting SANM. After the diagnosis, she received methylprednisolone pulse therapy (mPSL, 1 g/day × 3 days, twice) and subsequent oral prednisolone therapy (PSL, 30 mg/day for 1 month, 25 mg/day for 1 month and 22.5 mg/day for 1 month), leading to improvement of her muscle weakness. One month after the PSL tapering to 20 mg/day, her muscle weakness deteriorated with oxygen desaturation (SpO2: 93% at room air) due to hypoventilation caused by weakness of respiratory muscles. BIPAP was used for the management of acute respiratory failure in combination with IVIG (20 g/day × 5 days) followed by mPSL pulse therapy (1 g/day × 3 days), oral PSL (30 mg/day × 3 weeks, then tapered to 25 mg/day) and tacrolimus (3 mg/day). Twenty-seven days after the start of BIPAP, she was weaned from BIPAP with improvement of muscle weakness, hypoxemia and hypercapnia. After she achieved remission with improvement of muscle weakness and reduction of serum CK level to a normal level, the dose of oral prednisolone was gradually tapered to 12.5 mg/day without relapse for 3 months. <br/>
Conclusions: Our report provides new insights into the role of immunosuppressants and biphasic positive airway pressure for induction of remission in patients with SANM.
No potential conflict of interest relevant to this article was reported.
Wiley
Acta Medica Okayama
2049-4173
7
5
2019
Late presented congenital myasthenic syndrome with novel compound heterozygous CHRNE mutations mimicking seronegative myasthenia gravis
288
290
EN
Yumiko
Nakano
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Keiichiro
Tsunoda
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Toru
Yamashita
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Jun
Mitsui
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kota
Sato
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Mami
Takemoto
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Nozomi
Hishikawa
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yasuyuki
Ohta
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Tatsushi
Toda
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Shoji
Tsuji
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Koji
Abe
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
We found a late presented congenital myasthenic syndrome (CMS) patient with novel CHRNE gene mutations. Although our patient has shown blepharoptosis since youth, fatigable muscle weakness began at age 71. Genetic analysis revealed novel compound heterozygous CHRNE mutations (c.1032+2T>G, c.1306_1307 delGA). His myasthenic symptoms were well managed by oral anti‐cholinesterase drug until he died at 82‐year‐old. The present case showed mild myasthenic symptoms with very late presentation and slow progression. Late presented CMS is often underdiagnosed; therefore, genetic testing is important to distinguish it from other myasthenic disease.
No potential conflict of interest relevant to this article was reported.
Wiley
Acta Medica Okayama
0360-4012
97
5
2018
Enhanced oxidative stress and the treatment by edaravone in mice model of amyotrophic lateral sclerosis
607
609
EN
Yasuyuki
Ohta
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Emi
Nomura
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Jingwei
Shang
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Tian
Feng
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yong
Huang
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Xia
Liu
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Xiaowen
Shi
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yumiko
Nakano
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Nozomi
Hishikawa
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kota
Sato
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mami
Takemoto
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Toru
Yamashita
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Koji
Abe
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Oxidative stress is associated with the degeneration of both motor neurons and skeletal muscles in amyotrophic lateral sclerosis (ALS). A free radical scavenger edaravone has been proven as a therapeutic drug for ALS patients, but the neuroprotective mechanism for the oxidative stress of ALS has not been fully investigated. In this study, we investigated oxidative stress in ALS model mice bearing both oxidative stress sensor nuclear erythroid 2-related factor 2 (Nrf2) and G93A-human Cu/Zn superoxide dismutase (Nrf2/G93A) treated by edaravone. In vivo Nrf2 imaging analysis showed the accelerated oxidative stress both in spinal motor neurons and lower limb muscles of Nrf2/G93A mice according to disease progression in addition to the enhancement of serum oxidative stress marker dROMS. These were significantly alleviated by edaravone treatment accompanied by clinical improvements (rotarod test). The present study suggests that in vivo optical imaging of Nrf2 is useful for detecting oxidative stress in ALS, and edaravone alleviates the degeneration of both motor neurons and muscles related to oxidative stress in ALS patients.
No potential conflict of interest relevant to this article was reported.
Wiley
Acta Medica Okayama
2049-4173
7
3
2019
Very rare solitary primary peripheral nerve onset cytotoxic molecule-positive peripheral T-cell lymphoma (PTCL)
146
149
EN
Namiko
Matsumoto
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kota
Sato
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yoshiaki
Takahashi
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yuko
Kawahara
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Taijun
Yunoki
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Jingwei
Shang
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mami
Takemoto
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Nozomi
Hishikawa
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yasuyuki
Ohta
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Toru
Yamashita
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Maiko
Sakamoto
Department of Hematology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Eisei
Kondou
Department of Hematology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Rei
Shibata
Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Tadashi
Yoshino
Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Toshifumi
Ozaki
Department of Orthopedic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Koji
Abe
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Here we present the first report of solitary primary peripheral nerve onset cytotoxic molecule (CM)-positive peripheral T-cell lymphoma (PTCL) diagnosed after nerve biopsy. An 84-year-old female with rheumatoid arthritis (RA) complained of asymmetric severe tenderness in her upper limbs. The biopsy pathology revealed a direct invasion of CM-positive PTCL. When RA patients complain of numbness, tenderness, or weakness, lymphomatic peripheral nerve invasion should be considered.
No potential conflict of interest relevant to this article was reported.
NPG
Acta Medica Okayama
2045-2322
9
1
2019
In vivo direct reprogramming of glial linage to mature neurons after cerebral ischemia
10956
EN
Toru
Yamashita
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Jingwei
Shang
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yumiko
Nakano
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ryuta
Morihara
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kota
Sato
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Mami
Takemoto
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Nozomi
Hishikawa
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yasuyuki
Ohta
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Koji
Abe
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
The therapeutic effect of in vivo direct reprogramming on ischemic stroke has not been evaluated. In the present study, a retroviral solution (1.5-2.0 × 107 /ul) of mock pMX-GFP (n = 13) or pMX-Ascl1/Sox2/NeuroD1 (ASN) (n = 14) was directly injected into the ipsilateral striatum and cortex 3 days after 30 min of transient cerebral ischemia. The reprogrammed cells first expressed neuronal progenitor marker Dcx 7 and 21 days after viral injection, then expressed mature neuronal marker NeuN. This was accompanied by morphological changes, including long processes and synapse-like structures, 49 days after viral injection. Meanwhile, therapeutic improvement was not detected both in clinical scores or infarct volume. The present study provides a future novel self-repair strategy for ischemic stroke with beneficial modifications of the inducer-suppressor balance.
No potential conflict of interest relevant to this article was reported.
IOS Press
Acta Medica Okayama
1387-2877
68
4
2019
Acute Anti-Inflammatory Markers ITIH4 and AHSG in Mice Brain of a Novel Alzheimer's Disease Model
1667
1675
EN
Xiaowen
Shi
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Xia
Liu
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Jingwei
Shang
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Ryuta
Morihara
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yumiko
Nakano
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Tian
Feng
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yong
Huang
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kota
Sato
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mami
Takemoto
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Nozomi
Hishikawa
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Toru
Yamashita
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Koji
Abe
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Alzheimer's disease (AD) is the most common dementia and a progressive neurodegenerative disorder aggravated by chronic hypoperfusion (HP). Since numerous evidence suggests that inflammation is related with AD pathology, we investigated the expression change of two anti-inflammatory markers, inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and alpha-2-HS-glycoprotein (AHSG), in a novel AD model (APP23) with HP at 12 month of age. As compared with wild type (WT, n = 10), immunohistochemical analysis showed a higher ITIH4 and a lower AHSG expressions in the cerebral cortex, hippocampus, and thalamus of the APP23 + HP group (n = 12) than the simple APP23 (n = 10) group (*p < 0.05 and **p < 0.01 versus WT; #p < 0.05 and # #p < 0.01 versus APP23). The present study provides an upregulation of anti-inflammatory ITIH4 and a downregulation of pro-inflammatory TNFα-dependent AHSG in a novel AD plus HP mice model.
No potential conflict of interest relevant to this article was reported.
Wiley
Acta Medica Okayama
2049-4173
7
3
2018
Multi‐modal combination therapy rescued a frequent ischemic stroke patient due to giant cell arteritis
132
135
EN
Yoshiaki
Takahashi
Departments of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
Kota
Sato
Departments of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
Namiko
Matsumoto
Departments of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
Yuko
Kawahara
Departments of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
Taijun
Yunoki
Departments of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
Jingwei
Shang
Departments of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
Mami
Takemoto
Departments of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
Nozomi
Hishikawa
Departments of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
Yasuyuki
Ohta
Departments of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
Toru
Yamashita
Departments of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
Koji
Abe
Departments of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
Ischemic stroke (IS) due to giant cell arteritis (GCA) is rare, but highly mortal. Here, we report a 72-year-old man who showed frequent IS with GCA. Initial therapy with prednisolone increased the frequency of IS, which disappeared after continuous multi-modal combination therapy with corticosteroids, immunosuppressive agents, antiplatelets, and statin. The present case was discharged with independent walk, suggesting that a multi-modal combination therapy rescued the GCA patient from frequent IS.
No potential conflict of interest relevant to this article was reported.
Elsevier
Acta Medica Okayama
10523057
28
10
2019
Twendee X Ameliorates Phosphorylated Tau, α-Synuclein and Neurovascular Dysfunction in Alzheimer's Disease Transgenic Mice With Chronic Cerebral Hypoperfusion
104310
EN
Xia
Liu
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Toru
Yamashita
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Jingwei
Shang
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Xiaowen
Shi
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Ryuta
Morihara
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yong
Huang
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kota
Sato
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mami
Takemoto
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Nozomi
Hishikawa
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yasuyuki
Ohta
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Koji
Abe
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
BACKGROUND:<br/>
The pathological impact of chronic cerebral hypoperfusion (CCH) on Alzheimer's disease (AD) is still poorly understood. In the present study, we investigated the role of CCH on an AD mouse model in phosphorylated tau and α-synuclein pathology, neurovascular unit, cerebrovascular remodeling, and neurovascular trophic coupling. Moreover, examined protective effect of a new antioxidant Twendee X (TwX).<br/>
METHODS:<br/>
APP23 mice were implanted to bilateral common carotid arteries stenosis with ameroid constrictors to gradually decrease the cerebral blood flow. The effects of the administration of TwX were evaluated by immunohistochemical analysis and Immunofluorescent histochemistry.<br/>
RESULTS:<br/>
The present study revealed that the expressions of phospho-tau and phospho-α-synuclein were significantly increased in the APP23 + CCH mice group as compared with wild type and APP23 mice groups (*P < .05 and ⁎⁎P < .01 versus WT; #P < .05 and ##P < .01 versus APP23). In addition, CCH significantly exacerbated MMP-9 activation relating to blood-brain barrier destruction (⁎⁎P < .01 versus WT; #P < .05, and ##P < .01 versus APP23), enhanced neurovascular remodeling, and impaired a neurovascular trophic coupling in the vascular endothelial BDNF expression of the APP23 + CCH group. TwX treatment (20 mg/kg/day, from 4.5 to 12 months) significantly reduced tau and α-synuclein pathologies, ameliorated neurovascular dysfunction compared with APP23 + CCH group.<br/>
CONCLUSIONS:<br/>
Our findings indicate that administration of a new antioxidative mixture TwX substantially reduced the above neuropathologic abnormalities, suggesting a potential therapeutic benefit of TwX for AD with CCH.
No potential conflict of interest relevant to this article was reported.
Elsevier
Acta Medica Okayama
10523057
28
7
2019
Clinical and Pathological Benefit of Twendee X in Alzheimer's Disease Transgenic Mice with Chronic Cerebral Hypoperfusion
1993
2002
EN
Xia
Liu
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Toru
Yamashita
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Jingwei
Shang
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Xiaowen
Shi
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Ryuta
Morihara
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yong
Huang
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kota
Sato
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Mami
Takemoto
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Nozomi
Hishikawa
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yasuyuki
Ohta
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Koji
Abe
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
BACKGROUND:<br/>
Multiple pathogeneses are involved in Alzheimer's disease (AD), such as amyloid-β accumulation, neuroinflammation, and oxidative stress. The pathological impact of chronic cerebral hypoperfusion on Alzheimer's disease is still poorly understood.<br/>
METHODS:<br/>
APP23 mice were implanted to bilateral common carotid arteries stenosis with ameroid constrictors for slowly progressive chronic cerebral hypoperfusion (CCH). The effects of the administration of Twendee X (TwX) were evaluated by behavioral analysis, immunohistochemical analysis, and immunofluorescent histochemistry.<br/>
RESULTS:<br/>
In the present study, chronic cerebral hypoperfusion, which is commonly found in aged Alzheimer's disease, significantly exacerbated motor dysfunction of APP23 mice from 5 months and cognitive deficit from 8 months of age, as well as neuronal loss, extracellular amyloid-β plaque and intracellular oligomer formations, and amyloid angiopathy at 12 months. Severe upregulations of oxidative markers and inflammatory markers were found in the cerebral cortex, hippocampus, and thalamus at 12 months. Twendee X treatment (20 mg/kg/d, from 4.5 to 12 months) substantially rescued the cognitive deficit and reduced the above amyloid-β pathology and neuronal loss, alleviated neuroinflammation and oxidative stress.<br/>
CONCLUSIONS:<br/>
The present findings suggested a potential therapeutic benefit of Twendee X for Alzheimer's disease with chronic cerebral hypoperfusion.
No potential conflict of interest relevant to this article was reported.
Elsevier
Acta Medica Okayama
0022510X
400
2019
A unique Japanese CPEO family with a novel homozygous m.14819 T > G (p. S25A) substitution
145
147
EN
Emi
Nomura
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yasuyuki
Ohta
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Koh
Tadokoro
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kota
Sato
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Ryo
Sasaki
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yoshiaki
Takahashi
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Toru
Yamashita
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mami
Takemoto
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Nozomi
Hishikawa
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yu-ichi
Goto
Medical Genome Center (MGC), Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience (NIN), National Center of Neurology and Psychiatry
Koji
Abe
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
No potential conflict of interest relevant to this article was reported.
Acta Medica Okayama
0360-4012
92
1
2014
Reducing Hemorrhagic Complication by Dabigatran Via Neurovascular Protection After Recanalization With Tissue Plasminogen Activator in Ischemic Stroke of Rat
46
53
EN
Syoichiro
Kono
Kentaro
Deguchi
Yoshio
Omote
Taijun
Yunoki
Toru
Yamashita
Tomoko
Kurata
Yoshio
Ikeda
Koji
Abe
This study assesses the risks and benefits of tissue plasminogen activator (tPA) treatment under oral anticoagulation with dabigatran compared with warfarin or vehicle control in transient middle cerebral artery occlusion (tMCAO). After pretreatment with warfarin (0.2 mg/kg/day), dabigatran (20 mg/kg/day), or vehicle (0.5% carboxymethyl cellulose sodium salt) for 7 days, tMCAO was induced for 120 min, followed by reperfusion and tPA (10 mg/kg/10 ml). Clinical parameters, including cerebral infarction volume, hemorrhagic volume, and blood coagulation, were examined. At 24 hr after reperfusion, markers for the neurovascular unit at the peri-ischemic lesion were immunohistochemically examined in brain sections, and MMP-9 activity was measured by zymography. Paraparesis and intracerebral hemorrhage volume were significantly improved in the dabigatran-pretreated group compared with the warfarin-pretreated group. A marked dissociation between astrocyte foot processes and the basal lamina or pericyte was observed in the warfarin-pretreated group, which was greatly improved in the dabigatran-pretreated group. Furthermore, a remarkable activation of MMP-9 in the ipsilateral warfarin-pretreated rat brain was greatly reduced in dabigatran-pretreated rats. The present study reveals that the mechanism of intracerebral hemorrhage with warfarin-pretreatment plus tPA in ischemic stroke rats is the dissociation of the neurovascular unit, including the pericyte. Neurovascular protection by dabigatran, which was first shown in this study, could partially explain the reduction in hemorrhagic complication by dabigatran reported from clinical study.
No potential conflict of interest relevant to this article was reported.
Acta Medica Okayama
0039-2499
43
6
2012
Clinical and Pathological Improvement in Stroke-Prone Spontaneous Hypertensive Rats Related to the Pleiotropic Effect of Cilostazol
1639
1646
EN
Yoshio
Omote
Kentaro
Deguchi
FengFeng
Tian
Hiromi
Kawai
Tomoko
Kurata
Toru
Yamashita
Yasuyuki
Ohta
Koji
Abe
Background and Purpose-Cerebral infarction is a major cause of death or decreasing activities of daily living. This study aimed to investigate the efficacy of commonly used antiplatelet drugs on stroke and motor and cognitive functions in relation to oxidative stress markers and insulin-like growth factor 1 receptor (IGF-1R).
Methods-Stroke-prone spontaneously hypertensive rats were treated with vehicle, aspirin, clopidogrel, and cilostazol from 8 to 10 weeks of age. Physiological parameters, regional cerebral blood flow, and serum lipids were examined. Motor and cognitive functions were evaluated weekly by the Rotorod and water maze task. Spontaneous infarct volume, oxidative stress markers for lipid, protein, and DNA at the ischemic boundary zone of spontaneous infarction, and the IGF-1R-positive cell ratio in the hippocampus were immunohistochemically examined in brain sections. IGF-1R beta expression in the hippocampus was assessed by Western blotting.
Results-The antiplatelet drugs, cilostazol and clopidogrel, reduced the spontaneous infarct volume more than aspirin. Only cilostazol improved motor and cognitive functions with a significant increase (P<0.05) in the memory-related IGF-1R-positive ratio and IGF-1R beta expression in the hippocampus. Cilostazol reduced the 4 oxidative stress markers in affected neurons in stroke-prone spontaneously hypertensive rats regardless of blood pressure, regional cerebral blood flow, or serum lipid levels.
Conclusions-The present results suggest that a possible pleiotropic effect of cilostazol resulted in the reduction of spontaneous infarct volume and preservation of motor and spatial cognitive functions. The increase of IGF-1R-positive cells in the hippocampal CA1 region could partly explain the preservation of spatial cognitive function in stroke-prone spontaneously hypertensive rats.
No potential conflict of interest relevant to this article was reported.
Acta Medica Okayama
0306-4522
221
2012
Strong neuroprotection with a novel platinum nanoparticle against ischemic stroke- andtissue plasminogen activator-related brain damages in mice
47
55
EN
M.
Takamiya
Y.
Miyamoto
T.
Yamashita
K.
Deguchi
Y.
Ohta
K.
Abe
Reactive oxygen species (ROS) are major exacerbation factor in acute ischemic stroke, and thrombolytic agent tissue plasminogen activator (tPA) may worsen motor function and cerebral infarcts. The platinum nanoparticle (nPt) is a novel ROS scavenger, and thus we examined the clinical and neuroprotective effects of nPt in ischemic mouse brains. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min and divided into the following four groups by intravenous administration upon reperfusion, vehicle, tPA, tPA + nPt, and nPt. At 48 h after tMCAO, motor function, infarct volume, immunohistochemical analyses of neurovascular unit (NVU), in vivo imaging of matrix metalloproteinase (MMP), and zymography for MMP-9 activity were examined. Superoxide anion generation at 2 h after tMCAO was also examined with hydroethidine (HEt). As a result, administration of tPA deteriorated the motor function and infarct volume as compared to vehicle. In vivo optical imaging of MMP showed strong fluorescent signals in affected regions of tMCAO groups. Immunohistochemical analyses revealed that tMCAO resulted in a minimal decrease of NAGO and occludin, but a great decrease of collagen IV and a remarkable increase of MMP-9. HEt stain showed increased ROS generation by tMCAO. All these results became pronounced with tPA administration, and were greatly reduced by nPt. The present study demonstrates that nPt treatment ameliorates neurological function and brain damage in acute cerebral infarction with neuroprotective effect on NVU and inactivation of MMP-9. The strong reduction of ROS production by nPt could account for these remarkable neurological and neuroprotective effects against ischemic stroke.
No potential conflict of interest relevant to this article was reported.