TEMPORAL CORRELATION MAPPING ANALYSIS OF THE HEMODYNAMIC PENUMBRA IN MUTANT MICE DEFICIENT IN ENDOTHELIAL NITRIC-OXIDE SYNTHASE GENE-EXPRESSION

Background and Purpose Mice containing deletions in the genes encoding nitric oxide (NO) synthase have been useful to dissect the role of NO in cerebral ischemia. We recently reported that mice lacking expressi on of the endothelial isoform of NO synthase (eNOS) develop larger inf arcts after middle cerebral artery occlusion. Because NO or a related product of NO synthase activity is important for relaxation of cerebra l blood vessels, we examined for possible hemodynamic differences in t he peri-ischemic zone of eNOS-deficient and wild-type mice after middl e cerebral artery occlusion using functional CT scanning techniques. M ethods Wild-type SV129 mice (n=10) and mice deficient in eNOS gene exp ression (n=10) were subjected to middle cerebral artery occlusion unde r halothane anesthesia. Thirty minutes after ischemia, functional CT s canning was performed with dynamic scanning protocols to measure the c erebral transit profiles of injected contrast agents. A temporal corre lation mapping technique was used to analyze the pattern of hemodynami c perturbations based on alterations in the shape of the cerebral tran sit profiles. Statistical thresholds defined the hemodynamic core and penumbra Results Hemodynamic deficits were more severe in the mutant t han wild-type mouse. When expressed as a percentage of the total insul t, core areas were significantly increased in mutant mice (39.8+/-3.7% ) Compared with wild types (28.8+/-3.4%). Conversely, areas of the hem odynamic penumbra were significantly smaller in mice deficient in eNOS activity (60.2+/-3.7%) than in wild-type mice (71.2+/-3.4%). Furtherm ore, the calculated relative perfusion index within the hemodynamic pe numbra was significantly lower in the group with eNOS gene deletion (3 5.6+/-1.5% in mutants versus 43.0+/-2.4% in wild types). Conclusions T hese data indicate that mice lacking eNOS expression show a greater de gree of hemodynamic compromise after middle cerebral artery occlusion and suggest that a product of eNOS activity (eg, NO) may protect brain after focal cerebral ischemia, possibly by improving blood flow withi n the penumbral zone.