Abstracts

RATIONALE: In the immature monkey brain, bicuculline methiodide (BMI) administration into the entorhinal cortex (EC) induced local limbic seizures, neuronal cell loss, and mossy fiber (MF) reorganization in the hippocampus. We have attempted to reproduce this model in rat so as to address issues associated with epileptogenesis and seizure-sensitivity in animals with prior limbic seizures and/or lesions. METHODS: In awake adult rats, BMI was administered unilaterally into the EC via an implanted cannula (0.05 ?g in 1 ?l, injected over ten minutes). Bilateral hippocampal electrodes were also implanted, and both behavioral and EEG activity were recorded for 1 hour following BMI administration. Animals were sacrificed at 1-16 weeks post-BM infusion, and histological analyses were carried out on EC and hippocampus. RESULTS: BMI injection into the EC elicited mild and short-lasting seizure behaviors, associated with electrographic seizures recorded from hippocampus. Spontaneous seizures were not detected during the 1 hr post-infusion monitoring period, and no seizures were seen during subsequent observation periods. Histological analysis using cresyl violet staining, zinc histochemistry, Fink-Heimer degeneration stain and immunocytochemistry for GFAP revealed no short-term (1-4 weeks) neuropathological changes within the hippocampus ipsilateral to the site of infusion. At a 4 month survival time, neuronal damage was observed in the subfield CA1, as was neuronal cell loss in the hilus, gliosis, and MF sprouting into the dentate inner molecular layer and stratum oriens of CA3. CONCLUSIONS: BMI infusion into the EC of adult rats induces brief seizure activity and associated hippocampal damage - e.g., neuronal cell loss, gliosis and synaptic reorganization. However, no spontaneous epileptic activity developed in these animals. These observations are consistent with results from parallel monkey studies, and suggest that these morphological changes are not sufficient for genesis of a chronic epileptic state. Supported by NIH grants NS 18895 and NS 35548.