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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:2581.)
© 1999 American Heart Association, Inc.

Editorial

On Ischemic Brain Injury in Genetically Altered Mice

Myron D. Ginsberg, MD¹

¹ Peritz Scheinberg Professor of Neurology, Director, Cerebral Vascular Disease Research Center, University of Miami School of Medicine, Miami, Fla
From the Department of Neurology, University of Miami School of Medicine, Miami, Fla.

Correspondence to Myron D. Ginsberg, MD, Peritz Scheinberg Professor of Neurology, Director, Cerebral Vascular Disease Research Center, University of Miami School of Medicine, PO Box 016960, Miami, FL 33101-6960. E-mail mdginsberg@stroke.med.miami.edu

In recent years, genetically altered mice, either overexpressing or deficient in specific gene products, have come to play a vital role in experimental studies designed to probe the molecular pathophysiology of ischemic brain injury. More than 100 such studies have been reported to date, and notable successes have been achieved in elucidating the roles of the neuronal,^{1 2} endothelial,³ and inducible^{4 5} isoforms of nitric oxide synthase and of the cytosolic (CuZn)^{6 7 8} and mitochondrial (Mn) forms^{9 10 11} of the antioxidant-defense enzyme superoxide dismutase in brain ischemia. Other studies of cerebral ischemia have used mutant mice to assess altered glutamate-receptor subunit composition,^{12 13} vascular adhesion molecules,^{14 15 16 17 18 19} gene products related to nuclear damage, cell death and survival, apoptosis,^{20 21 22 23} transcription factors and early-response genes,^{24 25 26 27} cytokines,^{28 29} and apolipoprotein E.^{30 31}

Experimental studies of cerebral ischemia are fraught with pitfalls, however, and this is particularly the case in studies comparing the responses of wild-type and mutant mice, in which it becomes essential that mice of all groups be bred on a similar genetic background. The importance of rigorous control of genetic background in mutant mouse studies has been emphasized repeatedly in recent publications.^{32 33} Elsewhere in this issue, Tabrizi and coworkers³⁴ confront this problem in a careful study designed to assess whether endogenous tissue plasminogen activator (tPA), in fact, is beneficial or detrimental in focal cerebral ischemia. An impetus to their study is the recent report of Wang et al,³⁵ which purported to demonstrate that mice deficient in tPA exhibited 50% smaller cerebral infarcts than did wild-type mice. As noted by . . . [Full Text of this Article]

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