Abstracts

Status epilepticus (SE) results in cell loss and abnormal neuronal circuits. Following SE there is evidence that on-going aberrant neuronal activity results in these pathological processes. We postulated that suppression of electrical activity following SE at the site of the epileptic focus will reduce seizure-induced damage. To achieve this goal tetradotoxin (TTX) was used to suppress electrical activity in the hippocampi bilaterally following SE. Adult Sprague Dawley rats (300-350g) (n = 13) experienced lithium-pilocarpine induced SE for 2 hours. Starting 12-18 hours after the SE 7 rats received continuous TTX (1 microM) infusions through cannulas implanted in the bilateral hippocampi for 5 hours for 4 days. EEG activity monitored continuously through intracerebral electrodes demonstrated that EEG activity was suppressed (from 200-300 [mu]V to 40-60 [mu]V). Attempts to suppress EEG activity further resulted in a high mortality rate. Six rats received normal saline (NS) for the same duration of time and had no EEG changes. Despite TTX or NS rats showed behavior and electrographic seizures during the first day of infusion. Rats had a progressive declince in spikes and sharp waves in the EEG during the course of the infusions. However, even on the last day of of the infusion interictal epileptiform activity was present in both groups. Rats were sacrificed 2 weeks after SE and the brains evaluated with Timm and thionin staining. Semi-quantitative scales were used to measure mossy fiber sprouting (0-5, from no sprouting to marked sprouting) and neuronal cell loss (0-4, from no cell loss to total loss of cellular architecture) in the hippocampi. There were no significant differences between TTX-treated and NS-treated rats in histology scores. Mossy fiber sprouting mean score for CA3 was 2.00 for TTX and 1.65 for the NS group. In the supergranaular region the score was 3.00 for TTX and 2.50 for the NS group. CA1, CA3 and hilus cell loss scores were 2.05, 2.05, 1.90 in the TTX groups versus 1.55, 1.55, 1.30 in the NS groups. There was a strong correlation between sprouting and cell loss scores. Despite suppression of EEG activity, there was no reduction of cell loss and mossy fiber sprouting in the TTX-treated animals. These results suggest that suppression of electrical activity following SE provides little neuroprotection for animals. In addition, our findings indicate that the majority of damage associated with SE occurs during or immediately after the SE. (Supported by Citizens United for Research in Epilepsy (C.U.R.E.) and NIH (NINDS)(NS044296))