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ID 49926
FullText URL
Author
Takamiya, M.
Miyamoto, Y.
Ohta, Y.
Abstract
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.
Keywords
platinum nanoparticle
cerebral ischemia
free radical scavenger
neuroprotection
matrix metalloproteinase-9
tissue plasminogen activator
Published Date
2012-09-27
Publication Title
Neuroscience
Volume
volume221
Start Page
47
End Page
55
ISSN
0306-4522
Content Type
Journal Article
Official Url
http://dx.doi.org/10.1016/j.neuroscience.2012.06.060
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/49728
language
英語
Copyright Holders
(c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
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author
Refereed
True
DOI
Web of Sience KeyUT