Published Online
on April 3, 2003

A more recent version of this article appeared on May 1, 2003

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Submitted on November 9, 2002
Accepted on November 26, 2002

Rapid Cerebral Ischemic Preconditioning in Mice Deficient in Endothelial and Neuronal Nitric Oxide Synthases

Dmitriy N. Atochin MD, PhD; Jeffrey Clark BA; Ivan T. Demchenko DSci; Michael A. Moskowitz MD; and Paul L. Huang MD, PhD^*

^* To whom correspondence should be addressed. E-mail: huangp{at}helix.mgh.harvard.edu.

Background and Purpose--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.

Key words: cerebral ischemia • ischemic preconditioning • mice, knockout • models, animal

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