Effect of TTX suppression of hippocampal activity following status epilepticus.

Abstract

Status epilepticus (SE) is a severe neurological condition that can result in brain damage. In animals, SE is associated with cell loss and aberrant synaptogenesis. These pathological processes appear to be activity-dependent and may continue after the SE has ended. 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, tetrodotoxin (TTX) was used to suppress electrical activity in the hippocampi bilaterally following SE. Adult rats experienced lithium-pilocarpine-induced SE for 2h while controls underwent sham-SE with saline injections. Starting 12h after the SE or sham-SE rats received either continuous TTX (1 microM) or saline infusions through cannulas implanted in the bilateral hippocampi for 5h daily for 4 days. TTX resulted in significant EEG suppression and reduction in spikes and sharp waves. Rats were sacrificed 2 weeks after SE and the brains examined for cell loss and sprouting. Rats receiving TTX following SE had significantly more cell loss as well as a trend toward more mossy fiber sprouting than saline-treated rats following SE. TTX injection in sham-SE rats caused no cell loss or mossy fiber sprouting. These results suggest that suppression of electrical activity following SE is detrimental.