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Effect of Endothelial Nitric Oxide Synthase Genotype on Outcomes after Experimental Thromboembolic Stroke
Author(s) -
Sazonova Irina Y,
Hoda Md Nasrul,
Zemskova Marina A,
Hess David C
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.398.7
Subject(s) - enos , medicine , nitric oxide , middle cerebral artery , nitric oxide synthase , stroke (engine) , knockout mouse , endocrinology , cerebral blood flow , cardiology , anesthesia , ischemia , mechanical engineering , receptor , engineering
Acute ischemic stroke is the one of leading causes of morbidity and mortality in the U.S. African Americans have higher risk of stroke incidence and death that is associated with endothelial dysfunction and reduced bioavailability of nitric oxide. We propose that endothelial nitric oxide synthase knockout (eNOS −/− ) or heterozygote (eNOS +/− ) mice may be a suitable model of African American stroke. Methods The eNOS −/− and C57BL/6J mice were crossed to obtain eNOS +/−MAT and eNOS +/−PAT offspring (30±3 weeks; 13 mice/group). Embolic stroke was initiated by injection of a thrombus to the right middle cerebral artery. Cerebral blood flow was recorded to confirm occlusion. At 24 hours, the neurological status and brains were analyzed. Results eNOS −/− mice were characterized by small litter size and high pup mortality. The final body weight was similar among eNOS +/−MAT , eNOS +/−PAT , and eNOS −/− mice, but significantly lower than in wild type mice (28.0±1.8 vs. 31.4±1.9; p<0.001). Cerebral blood flow, infarct size, and neurological scores were comparable in all groups. However, all nitric oxide knockout mice had markedly increased mortality compared with wild type mice (46% vs. 23%). Conclusion eNOS −/− or eNOS +/− mice may be used as a model of the cerebrovascular complications associated with abnormalities in nitric oxide signaling as seen in African Americans. Research support: NIH‐R21 award and GHSU start‐up to I.Y.S.