Light and electron microscopic study of the toxic effect of kainic acid on pyramidal cells in the rat hippocampal formation.

Kainic acid was injected into the rat peritoneal cavity or lateral ventricle, and its toxic effect on pyramidal cells in the hippocampal formation was observed by light and electron microscopy. Pyramidal cells in areas CA3 and CA4 showed two types of degeneration 3 hr after the intraperitoneal administration of 2 mg of kainic acid. One type was vacuolar degeneration, in which the cells became bright with scanty cytoplasm. In the other type, the cells became dark with pyknosis and electron dense cytoplasm. As the dose of kainic acid was increased, the number of dark degenerated cells increased. One hr after the administration of 0.3 μg of kainic acid into the lateral ventricle, bright and vacuolated cells were observed, and later, dark cells also appeared. Both types of degeneration were observed electron microscopically 30 min after the intraperitoneal administration of 4 mg of kainic acid. Later, dark cells increased in number. Fifteen min after the administration into the lateral ventricle, both types of degeneration were observed, and the subsequent course was similar as with the intraperitoneal administration. Pyramidal cells in areas CA1 and CA2, and granular cells in the gyrus dentatus, did not show any degeneration. Mossy fiber endings did not show any degeneration either, and the distribution of zinc in these fibers observed by Timm's method did not change. From these results, the relationship between the dose and the effect of kainic acid and the mechanism of its toxic action were discussed.