Progressive neuronal loss induced by kindling: a possible mechanism for mossy fiber synaptic reorganization and hippocampal sclerosis

Kindling of limbic structures induces synaptic reorganization of the mossy fiber pathway in the dentate gyrus. To evaluate the hypothesis that kindling stimulation may also cause neuronal loss in the hilus of the dentate gyrus that could play a role in this synaptic reorganization, neuron counts were obtained using quantitative stereological methods in the hilar polymorphic region of rats kindled by perforant path stimulation. After 3 kindled generalized tonic clonic seizures, there was 12.7% neuronal loss in the hilar polymorphic region compared to controls, but there was no visually apparent lesion. After 30 generalized kindled seizures, the neuronal loss was 40.1%, was visually apparent, and resembled one aspect of the pattern of hilar neuronal loss observed in human hippocampal sclerosis. The results demonstrate that brief sporadic seizures can induce neuronal loss in the hippocampal formation, a brain region implicated in epilepsy, memory, and cognition.