Abstracts

Rationale: Although the hippocampus is frequently identified as an epileptic focus in patients with temporal lobe epilepsy, neuropathology studies of similar patients have shown damage to other areas including parahippocampal regions (e.g. entorhinal cortex), amygdala, and areas outside the temporal lobe. Similar neuronal death occurs in most animal models of acquired epilepsy in the adult brain and, because of the traditional focus on the hippocampus, these models have been used to study how the hippocampal lesion may contribute to the development of epilepsy. In acquired epilepsy models in juvenile animals, where the brain is more resistant to neuronal loss and less likely to develop epilepsy, the evidence that hippocampal death contributes to epileptogenesis is less clear. The inability to demonstrate a relationship between hippocampal damage and the development of epilepsy raises the possibility that other cortical structures not typically examined may be important for epileptogenesis in the immature brain. Methods: This study used the chemoconvulsant lithium pilocarpine model of status epilepticus in immature animals to assess more comprehensively which structures outside the hippocampal formation are injured acutely after prolonged status epilepticus. Sprague Dawley rat pups were implanted with surface EEG electrodes, and status epilepticus was induced at 20 days of age with the chemoconvulsant lithium pilocarpine. After 72 h, brain tissue from 12 animals was examined with Fluoro-Jade B, a histochemical marker for degenerating neurons, and compared to control animals that did not receive lithium pilocarpine. Results: Lithium pilocarpine provoked prolonged status epilepticus that was studied with both electrographic recording and behavior. All treated animals demonstrated Fluoro-Jade B staining in areas outside the hippocampus. The severity of neuronal degeneration was variable across animals, but still revealed a consistent pattern of damage that identified several brain regions and nuclei. The most prominent staining was seen in thalamus (mediodorsal, paratenial, reuniens, and ventral lateral geniculate nuclei), amygdala (ventral lateral, posteromedial, basomedial nuclei), ventral premammillary nucei of hypothalamus, and paralimbic cortices (perirhinal, entorhinal, and piriform) as well as parasubiculum and dorsal endopiriform nuclei. Conclusions: These results demonstrate that lithium pilocarpine-induced status epilepticus in the immature rat brain consistently results in neuronal injury outside of the hippocampus proper. These regions may be critical to the development of epilepsy in the immature brain.