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(Stroke. 1999;30:134-139.)
© 1999 American Heart Association, Inc.
Original Contributions |
Mice Deficient in Mac-1 (CD11b/CD18) Are Less Susceptible to Cerebral Ischemia/Reperfusion Injury
From the Department of Anesthesia, Children's Hospital, Boston (S.G.S., P.R.H.), and CNS Research Institute and Department of Neurosurgery (Y.F.W., S.A.L.) and Department of Pathology (A.C., M.P.F., T.M.N.), Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. Dr Soriano and Dr Coxon contributed equally to this work.
Correspondence to Sulpicio G. Soriano, MD, Department of Anesthesia, Children's Hospital, 300 Longwood Ave, Boston, MA 02115. E-mail soriano{at}A1.tch.harvard.edu
Background and Purpose—Macrophage-1 antigen (Mac-1) (CD11b/CD18), a leukocyte ß2 integrin, facilitates neutrophil adhesion, transendothelial migration, phagocytosis, and respiratory burst, all of which may mediate reperfusion-induced injury to ischemic brain tissue in conditions such as stroke. To determine the role of Mac-1 during ischemia and reperfusion in the brain, we analyzed the effect of transient focal cerebral ischemia in mice genetically engineered with a specific deficiency in Mac-1.
Methods—Transient focal ischemia/reperfusion was induced by occluding the left middle cerebral artery for 3 hours followed by a 21-hour reperfusion period in Mac-1–deficient (n=12) and wild-type (n=11) mice. Regional cerebral blood flow was determined with a laser-Doppler flowmeter. Brain sections were stained with 2% 2,3,5-triphenyltetrazolium chloride to determine the infarct volume. Neutrophil accumulation was determined by staining the brain sections with dichloroacetate esterase to identify neutrophils.
Results—Compared with the wild-type cohort, Mac-1–deficient mice had a 26% reduction in infarction volume (P<0.05). This was associated with a 50%, but statistically insignificant, reduction in the number of extravasated neutrophils in the infarcted areas of the brains in the mutant mice. There were no differences in regional cerebral blood flow between the 2 groups.
Conclusions—Mac-1 deficiency reduces neutrophil infiltration and cerebral cell death after transient focal cerebral ischemia. This finding may be related to a reduction in neutrophil extravasation in Mac-1–deficient mice.
Editorial Comment
Department of Neurosurgery, Stanford University, Palo Alto, California
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