DOI: 10.1161/01.str.27.8.1381. Temporal Correlation Mapping Analysis of the Hemodynamic Penumbra in Mutant Mice Deficient in Endothelial Nitric Oxide Synthase Gene Expression

Temporal Correlation Mapping Analysis of the Hemodynamic Penumbra in Mutant Mice Deficient in Endothelial Nitric Oxide Synthase Gene Expression

10.1161/01.str.27.8.1381

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Stroke (276)

Abstract

Background and PurposeMice 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.MethodsWild-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.ResultsHemodynamic 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).ConclusionsThese 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.

Bibliography

Lo, E. H., Hara, H., Rogowska, J., Trocha, M., Pierce, A. R., Huang, P. L., Fishman, M. C., Wolf, G. L., & Moskowitz, M. A. (1996). Temporal Correlation Mapping Analysis of the Hemodynamic Penumbra in Mutant Mice Deficient in Endothelial Nitric Oxide Synthase Gene Expression. Stroke, 27(8), 1381â1385.

Authors 9

Eng H. Lo (first)
Hideaki Hara (additional)
Jadwiga Rogowska (additional)
Marek Trocha (additional)
Allen R. Pierce (additional)
Paul L. Huang (additional)
Mark C. Fishman (additional)
Gerald L. Wolf (additional)
Michael A. Moskowitz (additional)

References 36 Referenced 77

10.1111/j.1750-3639.1994.tb00810.x
Dawson DA. Nitric oxide and focal cerebral ischemia: multiplicity of actions and diverse outcomes. Cerebrovasc Brain Metab Rev. 1994;6:299-324. / Cerebrovasc Brain Metab Rev (1994)
10.1161/str.25.3.7510430
10.1038/jcbfm.1994.25
Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev. 1991;43:109-142. (10.1016/S0031-6997(25)06663-3) / Pharmacol Rev (1991)
10.1097/00004647-199607000-00010
10.1126/science.7522345
Huang Z, Huang PL, Fishman MC, Moskowitz MA. Focal cerebral ischemia in mice deficient in either endothelial (eNOS) or neuronal nitric oxide (nNOS) synthase. Stroke. 1996;27:173. Abstract. / Stroke (1996)
10.1038/jcbfm.1994.123
Morikawa E, Moskowitz M, Huang C, Yoshida T, Irikura K, Dalkara T. l-Arginine infusion promotes nitric oxide-dependent vasodilation, increases rCBF, and reduces infarct volume in rats. Stroke. 1993;25:429-435. / Stroke (1993)
Morikawa E, Huang Z, Rosenblatt S, Yoshida T, Moskowitz MA. Therapeutic potential of l-arginine, a precursor of nitric oxide in focal ischemia. Br J Pharmacol. 1994;107:905-908. / Br J Pharmacol (1994)
10.1038/jcbfm.1994.28
Huang Z Huang PL Ma J Meng W Ayata C Fishman MC Moskowitz MA. Enlarged infarcts in endothelial nitric oxide synthase knockout mice are attenuated by nitro-l-arginine. J Cereb Blood Flow Metab. In press.
Lo EH, Rogowska J, Bogorodzki P, Trocha M, Matsumoto K, Saffran BN, Wolf GL. Temporal correlation analysis of penumbral dynamics in focal cerebral ischemia. J Cereb Blood Flow Metab. 1995;16:60-68. / J Cereb Blood Flow Metab (1995)
Lo EH Rogowska J Bogorodzki P Trocha M Matsumoto K Saffran BN Wolf GL. A new method for imaging the penumbra in focal ischemia: temporal evolution and correlation with histologic outcomes. J Cereb Blood Flow Metab. 1995;15(suppl 1):s324. Abstract.
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10.1109/42.414613
Rogowska J, Lo EH, Bogorodzki P, Trocha M, Wolf GL. New temporal correlation techniques for imaging the penumbra in stroke. Pharm Res. 1995;12:s102. Abstract. / Pharm Res (1995)
10.1161/res.10.3.393
10.1148/radiology.137.3.7003648
Goetze AHG, Bock JC, Heyer C, Weinmann HJ, Felix R. Experimental validation of susceptibility-contrast cerebral blood flow measurement by a microsphere reference method. Proc Soc Magn Reson. 1994;1:446. Abstract. / Proc Soc Magn Reson (1994)
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10.1002/mrm.1910290420
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Soher BJ, Gillard JH, Barker PB, Oppenheimer SM, Bryan RN. Dynamic GdDTPA MRI in acute stroke: comparison of relative cerebral blood volume and bolus arrival times. Proc Am Soc Neuroradiol. 1995;33:22. Abstract. / Proc Am Soc Neuroradiol (1995)
Warach S, Wielopski P, Edelman R. Identification and characterization of the ischemic penumbra of acute human stroke using echo-planar diffusion and perfusion imaging. Soc Magn Reson Med Abstr. 1993;12:249. Abstract. / Soc Magn Reson Med Abstr (1993)
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10.1016/0092-8674(93)90615-W
10.1038/377239a0
10.1016/0092-8674(95)90085-3
10.1126/science.7522345
Huang Z, Huang PL, Fishman MC, Moskowitz MA. Focal cerebral ischemia in mice deficient in either endothelial (eNOS) or neuronal nitric oxide (nNOS) synthase. Stroke.. 1996;27:173. Abstract. / Stroke. (1996)
10.1161/str.27.6.1124

Dates

Type	When
Created	14 years, 2 months ago (June 17, 2011, 4:08 p.m.)
Deposited	5 months, 3 weeks ago (March 6, 2025, 3:33 a.m.)
Indexed	5 months, 3 weeks ago (March 6, 2025, 4:10 a.m.)
Issued	29 years ago (Aug. 1, 1996)
Published	29 years ago (Aug. 1, 1996)
Published Print	29 years ago (Aug. 1, 1996)

Funders 0

None

BibTeX

@article{Lo_1996, title={Temporal Correlation Mapping Analysis of the Hemodynamic Penumbra in Mutant Mice Deficient in Endothelial Nitric Oxide Synthase Gene Expression}, volume={27}, ISSN={1524-4628}, url={http://dx.doi.org/10.1161/01.str.27.8.1381}, DOI={10.1161/01.str.27.8.1381}, number={8}, journal={Stroke}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Lo, Eng H. and Hara, Hideaki and Rogowska, Jadwiga and Trocha, Marek and Pierce, Allen R. and Huang, Paul L. and Fishman, Mark C. and Wolf, Gerald L. and Moskowitz, Michael A.}, year={1996}, month=aug, pages={1381–1385} }

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  "abstract": "<jats:p><jats:italic>Background and Purpose</jats:italic>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.</jats:p><jats:p><jats:italic>Methods</jats:italic>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.</jats:p><jats:p><jats:italic>Results</jats:italic>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\u00b13.7%) compared with wild types (28.8\u00b13.4%). Conversely, areas of the hemodynamic penumbra were significantly smaller in mice deficient in eNOS activity (60.2\u00b13.7%) than in wild-type mice (71.2\u00b13.4%). Furthermore, the calculated relative perfusion index within the hemodynamic penumbra was significantly lower in the group with eNOS gene deletion (35.6\u00b11.5% in mutants versus 43.0\u00b12.4% in wild types).</jats:p><jats:p><jats:italic>Conclusions</jats:italic>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.</jats:p>",
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