Abstracts

Rationale: Many animal models of acquired epilepsy have demonstrated that the immature brain is more resistant to seizure-induced neuronal injury than the adult brain. Flouro-Jade B is a histochemical marker that can be used to detect evidence of early neuronal injury. We utilized this marker to test the hypothesis that the immature rat brain is resistant to neuronal injury in an animal model of chemoconvulsant-status epilepticus. Methods: 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 hours, brain tissue from 13 different animals was examined with Flouro-Jade B and compared to control animals that did not receive lithium pilocarpine. Both coronal (n=7) and horizontal (n=6) sections were obtained in order to optimize visualization of the dorsal or ventral hippocampal formation respectively. Results: Lithium pilocarpine provoked prolonged status epilepticus that could be observed by both electrographic EEG recording and clinical behavior. All treated animals demonstrated Flouro-Jade B staining. This staining was observed consistently in the thalamus, amygdala, and regions of the hippocampal formation. Horizontal sections favoring a view of the ventral hippocampus showed marked Flouro-Jade B staining in CA1, CA3, and hilar region of the hippocampal formation. Coronal sections favoring a view of the dorsal hippocampus did not consistently show as robust a staining pattern in these regions. However, even in coronal sections with little to no staining in the dorsal hippocampus, definite staining in the ventral hippocampus could be observed despite distortions in the anatomical orientation. Conclusions: These results demonstrate that lithium pilocarpine-induced status epilepticus consistently results in neuronal injury in the immature rat brain. Specific susceptible anatomic regions include the ventral hippocampus, thalamus, and amygdala. By contrast, the dorsal hippocampus is relatively more resistant to neuronal injury. Neuronal injury in the hippocampal formation is more easily observed in horizontal sections which favor an optimal visualization of the ventral hippocampus. (Supported by the PCMC Foundation Innovative Research Grant, a CHRCDA grant, and NIH contract NO1-NS-4-2359).