Posthypoxic treatment with MK-801 reduces hypoxic-ischemic damage in the neonatal rat.
We evaluated the neuroprotective effect of MK-801, a noncompetitive, selective N-methyl-D-aspartate receptor antagonist, in a neonatal hypoxic-ischemic animal model. Seven-day-old rats underwent bilateral ligation of the carotid arteries followed by exposure to an 8% oxygen atmosphere for 1 hr. We sacrificed the animals 72 hrs later and assessed the hypoxic-ischemic brain damage histologically. MK-801 (10 mg/kg), administered IP 0.5 hr before the hypoxia, completely prevented hypoxic-ischemic infarction in cerebral cortex, while treatment immediately and 1 hr after the end of the hypoxia resulted in 76% and 52% reduction in the infarcted area, respectively. MK-801, given 0.5 hr before and immediately after the insult, reduced striatal damage and, given 0.5 hr before, attenuated neuronal necrosis in hippocampal regions. These results show that in neonates MK-801 is neuroprotective even when administered up to 1 hr after the end of a hypoxic-ischemic insult.
Hattori
H
H
Epilepsy and Neurology Research Laboratories, Veterans Administration Medical Center, Sepulveda, CA 91343.
Morin
A M
AM
Schwartz
P H
PH
Fujikawa
D G
DG
Wasterlain
C G
CG
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001921:Brain / Q000473:pathology*; D001925:Brain Damage, Chronic / Q000209:etiology* / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy*; D003986:Dibenzocycloheptenes / Q000627:therapeutic use*; D016291:Dizocilpine Maleate; D000860:Hypoxia / Q000150:complications / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains
D003986:Dibenzocycloheptenes; D016291:Dizocilpine Maleate