Present address of Dr. Koh: Box 51, Division of Neurology, Children's Memorial Hospital, Feinberg School of Medicine, Northwestern University, 2300 Children's Plaza, Chicago, IL 60614, U.S.A.
NBQX or Topiramate Treatment after Perinatal Hypoxia-induced Seizures Prevents Later Increases in Seizure-induced Neuronal Injury
Article first published online: 14 MAY 2004
Volume 45, Issue 6, pages 569–575, June 2004
How to Cite
Koh, S., Tibayan, F. D., Simpson, J. N. and Jensen, F. E. (2004), NBQX or Topiramate Treatment after Perinatal Hypoxia-induced Seizures Prevents Later Increases in Seizure-induced Neuronal Injury. Epilepsia, 45: 569–575. doi: 10.1111/j.0013-9580.2004.69103.x
- Issue published online: 14 MAY 2004
- Article first published online: 14 MAY 2004
- Accepted February 3, 2004.
- Neonatal seizures;
- Cell death;
Summary: Purpose: To evaluate the efficacy of NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f) quinoxaline-2,3-dione) and topiramate (TPM) given after hypoxia-induced seizures in preventing the delayed effect of hypoxia on subsequent susceptibility to seizures and neuronal injury.
Methods: We used “two-hit” rodent seizure model to study the long-term effect of perinatal hypoxia on later kainate (KA) seizure-induced neuronal damage and investigated the therapeutic efficacy of a postseizure treatment protocol in reversing the conditioning effect of early-life seizures.
Results: Hypoxia at P10 induces seizures without cell death but causes an increase in susceptibility to second seizures induced by KA as early as 96 h after hypoxia, and this lowered seizure threshold persists to adulthood. Furthermore, perinatal hypoxia increases KA-induced neuronal injury at postnatal day (P)21 and 28/30. Repeated doses of NBQX (20 mg/kg) or TPM (30 mg/kg) given for 48 h after hypoxia-induced seizures prevent the increase in susceptibility to KA seizure-induced hippocampal neuronal injury at P28/30.
Conclusions: Our results suggest that α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor blockade after hypoxia prevents the priming effect of perinatal hypoxia-induced seizures and that this protection occurs independent of its anticonvulsant action.