Vigabatrin Directed Against Kindled Seizures following Cortical Insult: Impact on Epileptogenesis and Somatosensory Recovery

Abstract

The anticonvulsant drug vigabatrin has not been found to be detrimental to the recovery process when administered following focal cortical insult. This finding is in contrast to the negative postinjury consequences of other anticonvulsant drugs (e.g., phenobarbital and diazepam) with more direct activation of the GABA/benzodiazepine receptor complex. Moreover, phenobarbital directed against kindled seizures affects functional recovery more adversely than either the drug or subconvulsive seizures alone. The purpose of the present study was to determine whether vigabatrin (150, 200, and 250 mg/kg) directed against kindled seizures would impact recovery from lesion-induced somatosensory deficits. Vigabatrin was coupled with daily electrical kindling of the amygdala during the first week after a unilateral anteromedial cortex (AMC) lesion. Somatosensory recovery was assessed using bilateral tactile stimulation tests. Animals receiving the highest dose of vigabatrin prior to electrical kindling (250 mg/kg vigabatrin/kindled) remained significantly impaired even after two months of testing relative to vehicle/kindled, kindled/250 mg/kg vigabatrin, which received vigabatrin after electrical kindling, and the 150, 200, and 250 mg/kg vigabatrin/nonkindled groups (p < 0.0001). In contrast, neither vigabatrin (at any of the doses tested) nor subconvulsive kindled seizures impacted the recovery process (p > 0.05) when administered alone (i.e., without the drug + seizure interaction). These data add to the accumulating experimental and clinical evidence suggesting that the neurobehavioral consequences of the interaction between anticonvulsant drugs and subclinical seizures after brain insult are detrimental to functional recovery.