(Stroke. 1996;27:1381-1385.)
© 1996 American Heart Association, Inc.
Articles |
Temporal Correlation Mapping Analysis of the Hemodynamic Penumbra in Mutant Mice Deficient in Endothelial Nitric Oxide Synthase Gene Expression
the Center for Imaging and Pharmaceutical Research and Department of Radiology (E.H.L., J.R., M.T., A.R.P., G.L.W.), the Stroke and Neurovascular Regulation Laboratory and Department of Neurology (H.H., M.A.M.), and the Cardiovascular Research Center and Department of Medicine (P.L.H., M.C.F.), Massachusetts General Hospital, Harvard Medical School, Boston, Mass.
Correspondence to Eng H. Lo, PhD, Center for Imaging and Pharmaceutical Research, Harvard Medical School, MGH East Bldg 149, Charlestown, MA 02129. E-mail eng@cipr.mgh.harvard.edu.
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 expression of the endothelial isoform of NO synthase (eNOS) develop larger infarcts after middle cerebral artery occlusion. Because NO or a related product of NO synthase activity is important for relaxation of cerebral blood vessels, we examined for possible hemodynamic differences in the peri-ischemic zone of eNOS-deficient and wild-type mice after middle cerebral artery occlusion using functional CT scanning techniques.
Methods Wild-type SV129 mice (n=10) and mice deficient in eNOS gene expression (n=10) were subjected to middle cerebral artery occlusion under halothane anesthesia. Thirty minutes after ischemia, functional CT scanning was performed with dynamic scanning protocols to measure the cerebral transit profiles of injected contrast agents. A temporal correlation mapping technique was used to analyze the pattern of hemodynamic perturbations based on alterations in the shape of the cerebral transit profiles. Statistical thresholds defined the hemodynamic core and penumbra.
Results Hemodynamic deficits were more severe in the mutant than wild-type mouse. When expressed as a percentage of the total insult, core areas were significantly increased in mutant mice (39.8±3.7%) compared with wild types (28.8±3.4%). Conversely, areas of the hemodynamic penumbra were significantly smaller in mice deficient in eNOS activity (60.2±3.7%) than in wild-type mice (71.2±3.4%). Furthermore, the calculated relative perfusion index within the hemodynamic penumbra was significantly lower in the group with eNOS gene deletion (35.6±1.5% in mutants versus 43.0±2.4% in wild types).
Conclusions These data indicate that mice lacking eNOS expression show a greater degree 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 within the penumbral zone.
Editorial Comment
Department of Neurosurgery and Neurology, University of California, School of Medicine, San Francisco, Calif
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