title: Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase.
abstract: The proposal that nitric oxide (NO) or its reactant products mediate toxicity in brain remains controversial in part because of the use of nonselective agents that block NO formation in neuronal, glial, and vascular compartments. In mutant mice deficient in neuronal NO synthase (NOS) activity, infarct volumes decreased significantly 24 and 72 hours after middle cerebral artery occlusion, and the neurological deficits were less than those in normal mice. This result could not be accounted for by differences in blood flow or vascular anatomy. However, infarct size in the mutant became larger after endothelial NOS inhibition by nitro-L-arginine administration. Hence, neuronal NO production appears to exacerbate acute ischemic injury, whereas vascular NO protects after middle cerebral artery occlusion. The data emphasize the importance of developing selective inhibitors of the neuronal isoform.
authors.affiliation: Stroke Research Laboratory, Massachusetts General Hospital, Charlestown 02129.
authors.forename: Z
authors.initials: Z
authors.lastname: Huang
authors.forename: P L
authors.initials: PL
authors.lastname: Huang
authors.forename: N
authors.initials: N
authors.lastname: Panahian
authors.forename: T
authors.initials: T
authors.lastname: Dalkara
authors.forename: M C
authors.initials: MC
authors.lastname: Fishman
authors.forename: M A
authors.initials: MA
authors.lastname: Moskowitz
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism*; D002544:Cerebral Infarction / Q000209:etiology*; D002560:Cerebrovascular Circulation; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D009474:Neurons / Q000201:enzymology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine
chemical_list: D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases