Graber K D, Prince D A
Department of Neurology and Neurological Sciences, Stanford University Medical Center, CA 94305-5300, USA.
Ann Neurol. 1999 Aug;46(2):234-42. doi: 10.1002/1531-8249(199908)46:2<234::aid-ana13>3.0.co;2-q.
Severe cortical trauma frequently causes epilepsy that develops after a long latency. We hypothesized that plastic changes in excitability during this latent period might be initiated or sustained by the level of neuronal activity in the injured cortex. We therefore studied effects of action potential blockade by application of tetrodotoxin (TTX) to areas of cortical injury in a model of chronic epileptogenesis. Partially isolated islands of sensorimotor 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 implanted over lesions. Ten to 15 days later neocortical slices were obtained through 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 from 4 rats had spontaneous epileptiform events. Only 2 of 11 lesioned animals and 6% of slices from cortex exposed to TTX in vivo exhibited evoked epileptiform potentials, and no spontaneous epileptiform events were observed. There was no evidence of residual TTX during recordings. TTX-Elvax was ineffective in reversing epileptogenesis when implanted 11 days after cortical injury. These data suggest that development of antiepileptogenic drugs for humans may be possible.
严重的皮质创伤常常会导致癫痫，且癫痫会在很长的潜伏期后发作。我们推测，在这个潜伏期内，兴奋性的可塑性变化可能是由受损皮质中神经元活动的水平启动或维持的。因此，我们在慢性癫痫发生模型中，通过向皮质损伤区域应用河豚毒素（TTX）来研究动作电位阻断的效果。在28至30日龄的雄性Sprague-Dawley大鼠中制作部分孤立的感觉运动皮质岛，并将含有TTX或对照载体的Elvax聚合物薄片植入损伤部位。10至15天后，通过分离物获取新皮质切片用于电生理研究。所有损伤部位与对照-Elvax接触的动物（n = 12）的切片（36个切片中的58%）均表现出诱发的癫痫样场电位，4只大鼠的切片有自发癫痫样事件。在体内暴露于TTX的皮质中，11只损伤动物中只有2只以及切片的6%表现出诱发的癫痫样电位，未观察到自发癫痫样事件。记录过程中没有TTX残留的证据。在皮质损伤11天后植入TTX-Elvax在逆转癫痫发生方面无效。这些数据表明，开发用于人类的抗癫痫药物可能是可行的。
