Abstracts

RATIONALE: A preferential and highly restricted lesion of EC layer III is observed 3 days after a focal injection of the indirect excitotoxin gamma-acetylenic GABA (GAG) into the rat entorhinal cortex (EC) (Exp. Neurol. 153:203-213, 1998). The present study was designed to explore the long-term effects of this lesion. METHODS: Adult male Sprague-Dawley rats (200-220g) received bilateral stereotaxic microinjections of GAG (4 g/3 e 0.33 l) into the EC as described previously (see ref. cited above). Three, 14 or 60 days later animals were perfused, and their brains were sectioned and processed for Nissl staining. Animals surviving for more than 60 days after the GAG treatment were also studied by continuous EEG recording to detect spontaneous seizures. RESULTS:During the first 3 days after bilateral GAG injections, all animals had behavioral seizures. Animals killed after 3 days showed bilateral neurodegeneration which was restricted to layer III of the EC, except that 2 of 14 rats also had a lesion in the hilus of the ventral hippocampus. After 14 days, all animals showed EC layer III lesions, additional hilar neuron loss, and variable lesions (hilus = CA1 > CA3 > granule cells) in the dorsal hippocampus. After 60 days, EEG recordings revealed spontaneous seizures in 100% of the rats. Upon histological examination, these older animals showed pronounced bilateral lesions in limbic brain regions. CONCLUSIONS: Our results suggest that restricted, bilateral lesions in layer III of the EC eventually cause more extensive neurodegeneration in the limbic system. The cumulative neuronal loss may be responsible for the occurence of spontaneous seizures weeks after intra-entorhinal GAG injections.