title: Rapid cerebral ischemic preconditioning in mice deficient in endothelial and neuronal nitric oxide synthases.
abstract: OBJECTIVE
  The purpose of this study was to test the hypothesis that nitric oxide is required for preconditioning in an intact animal model of focal ischemia using neuronal and endothelial nitric oxide synthase (nNOS and eNOS) knockout mice.
  
  
  METHODS
  Cerebral blood flow was measured in wild-type, nNOS knockout, and eNOS knockout mice by hydrogen clearance (absolute) and laser Doppler flowmetry (relative). Mice were preconditioned by three 5-minute episodes of transient middle cerebral artery occlusion (MCAO) and subjected to permanent MCAO. Neurological deficit and infarct size were determined 24 hours later.
  
  
  RESULTS
  Although wild-type mice showed protection from ischemic preconditioning, neither eNOS nor nNOS knockout mice showed protection. Laser Doppler measurements indicated that the relative blood flow decreases in core ischemic areas were the same in all groups.
  
  
  CONCLUSIONS
  Neither eNOS nor nNOS knockout mice show protection from rapid ischemic preconditioning, suggesting that nitric oxide may play a role in the molecular mechanisms of protection.
authors.affiliation: Cardiology Division, Cardiovascular Research Center, Massachusetts General Hospital East, Charlestown, MA 02129, USA.
authors.forename: Dmitriy N
authors.initials: DN
authors.lastname: Atochin
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Clark
authors.forename: Ivan T
authors.initials: IT
authors.lastname: Demchenko
authors.forename: Michael A
authors.initials: MA
authors.lastname: Moskowitz
authors.forename: Paul L
authors.initials: PL
authors.lastname: Huang
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology / Q000517:prevention & control*; D002560:Cerebrovascular Circulation; D003342:Corpus Striatum / Q000098:blood supply; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005838:Genotype; D020244:Infarction, Middle Cerebral Artery / Q000201:enzymology* / Q000473:pathology; D019194:Ischemic Preconditioning; D017078:Laser-Doppler Flowmetry; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010296:Parietal Lobe / Q000098:blood supply; D013997:Time Factors
chemical_list: D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496315:Nos3 protein, mouse