title: Attenuated hippocampal damage after global cerebral ischemia in mice mutant in neuronal nitric oxide synthase.
abstract: To address the importance of nitric oxide or its reaction products as mediators of neurotoxicity in brain, tissue injury was assessed after transient global ischemia in mice rendered mutant in the gene for neuronal nitric oxide synthase. Halothane-anesthetized wild type and mutant mice were subjected to temporary occlusion of the basilar plus both carotid arteries for 5 or 10 min followed by three days of reperfusion. Hippocampal injury, assessed both by qualitative grading and by cell counting in the CA1 subregion, was significantly less in the mutant mice group after 5 or 10 min of ischemia. Mutant mice exhibited a lower mortality (P < 0.01), less weight loss, more normal grooming and spontaneous motor activity and better grasping in the 10 min group. There were no obvious differences in cerebrovascular anatomy or hemodynamics between wild type and mutant mice. The data suggest that a deficiency of neuronal nitric oxide synthase confers increased resistance to transient global cerebral ischemia, and support the suggestion that selective neuronal nitric oxide synthase inhibitors might reduce tissue injury associated with global cerebral ischemia.
authors: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston 02129, USA.
authors: N
authors: N
authors: Panahian
authors: T
authors: T
authors: Yoshida
authors: P L
authors: PL
authors: Huang
authors: E T
authors: ET
authors: Hedley-Whyte
authors: T
authors: T
authors: Dalkara
authors: M C
authors: MC
authors: Fishman
authors: M A
authors: MA
authors: Moskowitz
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D002244:Carbon; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009154:Mutation / Q000502:physiology*; D009474:Neurons / Q000201:enzymology* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics*; D013997:Time Factors
chemical_list: D002244:Carbon; D019001:Nitric Oxide Synthase