Abstracts

RATIONALE: Neuronal death in the hippocampus is commonly found in patients with temporal lobe epilepsy (TLE) and is believed to contribute to the abnormal activity of the remaining neurons. Animal models of TLE display similar patterns of neuronal loss, most noticeably in the hilar, CA1, and CA3 regions of the hippocampus. Kainate is a glutamate analogue that has been shown to induce chronic seizures in rats. Pilocarpine, a muscarinic agonist, also causes chronic seizures when administered to rats. We hypothesize that the amount of neuron loss in the hilar, CA1, and CA3 regions is similar in these two different models of TLE. METHODS: This study used unbiased stereological procedures to evaluate hippocampal neuronal loss in kainate- and pilocarpine-treated rats. The kainate-treated rats received multiple doses of kainate (5 mg/kg, i.p.) to induce status epilepticus, while the pilocarpine-treated rats received one large dose of pilocarpine (320 mg/kg, i.p.). Controls were age-matched and treated with saline using either multiple or single intraperitoneal injections. The rats were monitored for seizures 6 h/wk and used for histological experiments only after spontaneous seizures were established (i.e., 2-4 mo after treatment). Quantitative analysis of every sixth 35-mm cresyl violet stained section was performed along the septotemporal axis by an individual blind to the treatment, using an optical fractionator (MicroBrightField, Baltimore, MD). RESULTS: Neuron loss was significantly greater in the CA1 region in the pilocarpine-treated rats compared to saline treatment throughout the septotemporal extent of the hippocampus, except in the most septal region. Kainate-treated rats showed an intermediate cell loss in CA1 that was not significantly different from saline or pilocarpine-treated rats. Cell loss in the hilar and CA3 regions of pilocarpine- and kainate-treated rats was only significantly different from saline treatment in the most temporal areas. CONCLUSIONS: This study found no substantial difference in hippocampal neuronal loss between the kainate and pilocarpine models of TLE. Supported by NINDS 16683