title: Neonatal mice lacking neuronal nitric oxide synthase are less vulnerable to hypoxic-ischemic injury.
abstract: We hypothesized that elimination of neuronal nitric oxide synthase (nNOS) by targeted disruption of the nNOS gene would result in amelioration of damage seen after hypoxia-ischemia in the developing brain since nitric oxide (NO) has been implicated in glutamate-mediated neurotoxicity after ischemia. Both wildtype and nNOS-deficient pups were subjected to focal ischemia followed by 1.5 h of hypoxia at Postnatal Day 7. Seven days later, brains of surviving animals were analyzed for damage. The nNOS-deficient pups (n = 17) had less histopathologic evidence of injury in both the hippocampus (P = 0.008) and the cortex (P = 0.0008) than the wildtype (n = 30) mice. When injured, the nNOS-deficient mice had damage that was limited to the hippocampus. These results support a role for neuronally produced NO in injury after perinatal hypoxia-ischemia.
authors.affiliation: Department of Neurology, University of California at San Francisco 94143, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Ferriero
authors.forename: D M
authors.initials: DM
authors.lastname: Holtzman
authors.forename: S M
authors.initials: SM
authors.lastname: Black
authors.forename: R A
authors.initials: RA
authors.lastname: Sheldon
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002545:Brain Ischemia / Q000201:enzymology* / Q000473:pathology; D002540:Cerebral Cortex / Q000201:enzymology / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology; D002534:Hypoxia, Brain / Q000201:enzymology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000201:enzymology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D009419:Nerve Tissue Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase