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Media type:
E-Article
Title:
Topiramate blocks perinatal hypoxia‐induced seizures in rat pups
Contributor:
Koh, Sookyong;
Jensen, Frances E.
Published:
Wiley, 2001
Published in:
Annals of Neurology, 50 (2001) 3, Seite 366-372
Language:
English
DOI:
10.1002/ana.1122
ISSN:
0364-5134;
1531-8249
Origination:
Footnote:
Description:
AbstractNeonatal 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.