Tetrodotoxin prevents posttraumatic epileptogenesis in rats

Severe cortical trauma frequently causes epilepsy that develops after a lon g latency. We hypothesized that plastic changes in excitability during this latent period might be initiated or sustained by the level of neuronal act ivity in the injured cortex. We therefore studied effects of action potenti al blockade by application of tetrodotoxin (TTX) to areas of cortical injur y in a model of chronic epileptogenesis. Partially isolated islands of sens orimotor cortex were made in 28- to 30-day-old male Sprague-Dawley rats and thin sheets of Elvax polymer containing TTX or control vehicle were implan ted over lesions. Ten to 15 days later neocortical slices were obtained thr ough isolates for electrophysiological studies. Slices from all animals (n = 12) with lesions contacted by control-Elvax (58% of 36 slices) exhibited evoked epileptiform field potentials, and those hom 4 rats had spontaneous epileptiform events. Only 2 of 11 lesioned animals and 6% of slices from co rtex exposed to TTX in vivo exhibited evoked epileptiform potentials, and n o spontaneous epileptiform events were observed. There was no evidence of r esidual TTX during recordings. TTX-Elvax was ineffective in reversing epile ptogenesis when implanted 11 days after cortical injury. These data suggest that development of anti-epileptogenic drugs for humans may be possible.