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NEUROLOGY 1989;39:713
© 1989 American Academy of Neurology

Posthypoxic treatment with MK-801 reduces hypoxic-ischemic damage in the neonatal rat

H. Hattori, MD, A. M. Morin, PhD, P. H. Schwartz, BSc, D. G. Fujikawa, MD and C. G. Wasterlain, MD

Epilepsy and Neurology Research Laboratories, Veterans Administration Medical Center, Sepulveda, CA (Drs. Hattori and Morin, Mr. Schwartz, and Drs. Fujikawa and Wasterlain)
Department of Neurology, Brain Research Institute, UCLA School of Medicine, Los Angeles, CA. (Drs. Hattori, Morin, Fujikawa, and Wasterlain)
Department of Neuroscience, Brain Research Institute, UCLA School of Medicine, Los Angeles, CA. (Mr. Schwartz and Dr. Wasterlain)
Division of Pediatric Intensive Care, Childrens Hospital of Los Angeles, USC School of Medicine, Los Angeles, CA. (Mr. Schwartz)

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.

Address correspondence and reprint requests to Dr. Hattori, Epilepsy Research Laboratory (111N1), Veterans Administration Medical Center, 16111 Plummer Street, Sepulveda, CA 91343.

Supported by Research Grant NS-13515 from NINCDS and by the Research Service of the Veterans Administration. MK-801 was a gift from Merck Sharp & Dohme Research Laboratories, West Point, PA.

Received September 15, 1988. Accepted for publication in final form November 10, 1988.




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