Rapid cerebral ischemic preconditioning in mice deficient in endothelial and neuronal nitric oxide synthases.
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.
Atochin
Dmitriy N
DN
Cardiology Division, Cardiovascular Research Center, Massachusetts General Hospital East, Charlestown, MA 02129, USA.
Clark
Jeffrey
J
Demchenko
Ivan T
IT
Moskowitz
Michael A
MA
Huang
Paul L
PL
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
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