Degeneration of hippocampal CA3 pyramidal cells induced by intraventricular kainic acid.
Degeneration of hippocampal CA3 pyramidal cells was investigated by light and electron microscopy after intraventricular injection of the potent convulsant, kainic acid. Electron microscopy revealed evidence of pyramidal cell degeneration within one hour. The earliest degenerative changes were confined to the cell body and proximal dendritic shafts. These included an increased incidence of lysosomal structures, deformation of the perikaryal and nuclear outlines, some increase in background electron density, and dilation of the cisternae of the endoplasmic reticulum accompanied by detachment of polyribosomes. Within the next few hours the pyramidal cells atrophied and became electron dense. Then these cells became electron lucent once more as ribosomes disappeared and their membranes and organelles broke up and disintegrated. Light microscopic changes correlated with these ultrastructural observations. The dendritic spines and the initial portion of the dendritic shaft became electron dense within four hours and degenerated rapidly, whereas the intermediate segment of the dendrites swelled moderately and became more electron lucent. No degenerative changes were evident in pyramidal cell axons and boutons until one day after kainic acid treatment. Less than one hour after kainic acid administration, astrocytes in the CA3 area swelled, initially in the vicinity of the cell body and mossy fiber layers. It is suggested that the paroxysmal discharges initiated in CA3 pyramidal cells by kainic acid served as the stimulus for this response. Phagocytosis commenced between one and three days after kainic acid administration, but remained incomplete at survival times of 6-8 weeks. Astrocytes, microglia, and probably oligodendroglia phagocytized the degenerating material. These results point to the pyramidal cell body and possibly also the dendritic spines as primary targets of kainic acid neurotoxicity. In conjunction with other data, they support the view that lesions made by intraventricular kainic acid can serve as models of epileptic brain damage.
Nadler, JV; Perry, BW; Gentry, C; Cotman, CW
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