Repeated brief epileptic seizures by pentylenetetrazole cause neurodegeneration and promote neurogenesis in discrete brain regions of freely moving adult rats

Abstract

Recurrent epileptic seizures are known to provoke various forms of cellular reorganization in the brains of humans and experimental animals. However, little is known about the mechanism of neuronal cell death resulting from epileptic seizures elicited by GABA antagonists. In the present study, we explored the effect on the central nervous systems of freely moving adult rats, of repeated brief epileptic seizures induced by systemic injection of pentylenetetrazole, a GABA-A receptor antagonist. Starting with minor convulsions, repeated epileptic seizures elicited a progressive increase in seizure severity, culminating in the fully kindled state. Histological examination showed that the epileptic seizures caused overt neuronal cell death in the limbic system, including the hippocampus and amygdala, and its adjoining cortex. During the recurrent epileptic seizures, neurogenesis occurred in the subgranular zone of the hippocampus, the subventricular zone of the lateral ventricle, and the amygdala. This type of pentylenetetrazole-induced neurogenesis was seen at an early stage of epileptogenesis in some regions in which massive cell loss was not evident. This suggests that neurogenesis is not a secondary consequence of neuronal cell death, but rather an independent effect of recurrent epileptic seizures.