NBQX or topiramate treatment after perinatal hypoxia-induced seizures prevents later increases in seizure-induced neuronal injury.
OBJECTIVE
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 alpha-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.
Koh
Sookyong
S
Department of Neurology, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Tibayan
Felicia D
FD
Simpson
Joelle N
JN
Jensen
Frances E
FE
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects; D002534:Hypoxia, Brain / Q000150:complications* / Q000209:etiology; D020287:In Situ Nick-End Labeling; D007608:Kainic Acid; D008297:Male; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D012640:Seizures / Q000139:chemically induced / Q000209:etiology* / Q000517:prevention & control*; D000077236:Topiramate
D000927:Anticonvulsants; D018696:Neuroprotective Agents; D011810:Quinoxalines; D018091:Receptors, AMPA; D000077236:Topiramate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D005632:Fructose; D007608:Kainic Acid