Abstracts

RATIONALE: Kainate-induced status epilepticus (SE) in rats causes massive neurodegeneration in limbic brain regions such as the piriform cortex and the hippocampus, reminiscent of sclerotic phenomena in human epileptic patients. Since these rats develop spontaneous complex partial seizures after 2-6 weeks, SE is considered a pathophysiological model of human temporal lobe epilepsy. Treatment with the NMDA receptor channel blocker dizolcipine (MK-801) before SE prevents neurodegeneration and spontaneous seizures. We previously demonstrated that MK-801 has a neuroprotective effect when applied after SE, suggesting that SE-induced limbic sclerosis is due to delayed cell death. We were now interested if neuroprotection by MK-801 prevents spontaneous recurrent seizures. METHODS: Adult female rats were intraperitoneally injected with 10 mg/kg kainate. About 35% of the rats developed a generalized SE which was interrupted by diazepam (5-6 mg/kg) after 90 min. Additionally, rats were i.p. injected with saline (control) or 0.1 mg/kg MK-801. The brains of all rats were histologically processed for detection of neurodegeneration (Nissl-staining) or DNA fragmentation (TUNEL staining) following perfusion after either 48 h after SE (MK-801: n=11, control: n=9) or 6 weeks after SE (MK-801: n=6, control: n=7). The latter group was observed for spontaneous seizures before sacrifice. RESULTS: Rats treated with MK-801 had a significantly smaller lesion and a reduced number of TUNEL-positive cells in the piriform cortex. A similar protection from SE-induced neurodegeneration was found in the hilus of the hippocampus. However, the neuroprotective effect seemed to be restricted to limbic brain regions because lesions in the substantia nigra were not reduced by MK-801. Surprisingly, the number of spontaneous recurrent seizures was higher in MK-801 treated rats compared to controls. CONCLUSIONS: Sclerotic phenomena in limbic brain regions after SE are mainly caused by delayed cell death, since MK-801 protects these regions when applied after SE. Neurodegeneration in limbic brain regions may not be a critical event for the development of temporal lobe epilepsy.