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Topiramate blocks perinatal hypoxia‐induced seizures in rat pups
Author(s) -
Koh Sookyong,
Jensen Frances E.
Publication year - 2001
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.1122
Subject(s) - topiramate , ampa receptor , anticonvulsant , kainate receptor , hypoxia (environmental) , epilepsy , anesthesia , medicine , encephalopathy , pharmacology , glutamate receptor , chemistry , receptor , oxygen , organic chemistry , psychiatry
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 ED 50 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.