Topiramate blocks perinatal hypoxia-induced seizures in rat pups
Article first published online: 15 JUL 2001
Copyright © 2001 Wiley-Liss, Inc.
Annals of Neurology
Volume 50, Issue 3, pages 366–372, September 2001
How to Cite
Koh, S. and Jensen, F. E. (2001), Topiramate blocks perinatal hypoxia-induced seizures in rat pups. Ann Neurol., 50: 366–372. doi: 10.1002/ana.1122
- Issue published online: 31 AUG 2001
- Article first published online: 15 JUL 2001
- Manuscript Accepted: 4 MAY 2001
- Manuscript Revised: 14 DEC 2000
- Manuscript Received: 19 JUL 2000
- NIH-NINDS. Grant Numbers: K08NS02068, R01NS-31718
- R. W. Johnson Pharmaceutical Research Institute
- MRRC-NICHD. Grant Number: P30 HD18655
Neonatal seizures caused by hypoxia can be refractory to conventional anticonvulsants. Currently, there is no effective postnatal intervention for newborn infants with hypoxic encephalopathy to prevent brain injury and long-term neurologic sequelae. We previously developed a rat model of perinatal hypoxia-induced seizures with subsequent long-term increases in seizure susceptibility and showed that these epileptogenic effects are selectively blocked by the α-amino-3-hydoxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist 6-nitro-7-sulfamoylbenzo(f)quinoxaline-2,3-dione. Using this model of perinatal seizures, we evaluated the efficacy of topiramate, a structurally novel anticonvulsant drug recently shown to attenuate AMPA/kainate currents. Topiramate effectively suppressed acute seizures induced by perinatal hypoxia in a dose-related manner with a calculated ED50 of 2.1mg/kg, i.p. Furthermore, in animals that had seizures suppressed by topiramate during acute hypoxia, there were no long-term increases in susceptibility to kainate-induced seizures and seizure-induced neuronal injury. Our results suggest that topiramate may have clinical potential as a therapeutic agent for refractory seizures in human neonates.