Stimulation-induced status epilepticus: role of the hippocampal mossy fibers in the seizures and associated neuropathology

Abstract

A study of seizure activity and neuronal cell death produced by intracerebroventricular kainic acid had suggested that seizures conveyed by the hippocampal mossy fibers are more damaging to CA3 pyramidal cells than seizures conveyed by other pathways. To test this idea, the effects of a unilateral mossy fiber lesion were determined on seizure activity and neuronal degeneration provoked by repetitive electrical stimulation of the hippocampal fimbria in unanesthetized rats. Fimbrial stimulation resulted in self-sustained status epilepticus accompanied by neuronal degeneration in several brain regions, including area CA3 of the hippocampal formation. A unilateral mossy fiber lesion more readily attenuated the electrographic and behavioral seizures provoked by fimbrial stimulation than those provoked by kainic acid. If status epilepticus developed in the presence of a mossy fiber lesion, denervated CA3 pyramidal cells were still destroyed, although similar lesions protect these neurons from kainic acid-induced status epilepticus. Thus the two models of status epilepticus employ somewhat different seizure circuitries and neurodegenerative mechanisms. Seizures which involve the mossy fiber projection are not necessarily more damaging to CA3 pyramidal cells than seizures which do not.