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 ischem ia. In this model, the ischemia resulted from I I min of cardiac arrest dur ing atraumatic chest compression. Resuscitated rats exhibit a characteristi c neurological syndrome characterized by sound-induced convulsions, specifi c motor and behavioral deficits, and death of hippocampal CAI pyramidal neu rons. 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 m g/kg) and seizure severity (P < 0.05 vs control at a dose of 10 mg/kg on th e fifth recovery day). The highest dose of topiramate (20 mg/kg iv) elimina ted nearly all histologic signs of hippocampal ischemic neuronal injury (P < 0.001). Phenytoin at 20 mg/kg iv exhibited neuroprotectant effects simila r 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 i mpairment; however, at 40 and 60 mg/kg iv both induced a mild impairment ty pical of most anticonvulsants. The results of this study support the concep t that topiramate possesses neuroprotective properties. (C) 2001 Elsevier S cience Inc. All rights reserved.