Topiramate as a neuroprotectant in a rat model of global ischemia-induced neurodegeneration

The neuroprotective properties of topiramate were evaluated in a rat model of stroke in which neurodegeneration was induced by temporary global ischemia. In this model, the ischemia resulted from I I min of cardiac arrest during atraumatic chest compression. Resuscitated rats exhibit a characteristic neurological syndrome characterized by sound-induced convulsions, specific motor and behavioral deficits, and death of hippocampal CAI pyramidal neurons. Topiramate, when administered iv 30 min after resuscitation, reduced the degree of motor impairment (P < 0.05 vs control at doses of 10 and 20 mg/kg) and seizure severity (P < 0.05 vs control at a dose of 10 mg/kg on the fifth recovery day). The highest dose of topiramate (20 mg/kg iv) eliminated nearly all histologic signs of hippocampal ischemic neuronal injury (P < 0.001). Phenytoin at 20 mg/kg iv exhibited neuroprotectant effects similar to those observed for topiramate at 20 mg/kg iv. In normal rats, neither topiramate nor phenytoin at 20 mg/kg iv induced any apparent neurological impairment; however, at 40 and 60 mg/kg iv both induced a mild impairment typical of most anticonvulsants. The results of this study support the concept that topiramate possesses neuroprotective properties. (C) 2001 Elsevier Science Inc. All rights reserved.