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Tetrodotoxin prevents posttraumatic epileptogenesis in rats
Author(s) -
Graber Kevin D.,
Prince David A.
Publication year - 1999
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/1531-8249(199908)46:2<234::aid-ana13>3.0.co;2-q
Subject(s) - epileptogenesis , tetrodotoxin , neuroscience , electrophysiology , cortex (anatomy) , epilepsy , medicine , anesthesia , local field potential , psychology
Abstract 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 anti epileptogenic drugs for humans may be possible. Ann Neurol 1999;46:234–242