on February 19, 2004
Published online before print February 19, 2004, doi: 10.1161/01.STR.0000116866.60794.21
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Submitted on September 30, 2003
From the Department of Neurology, Ludwig-Maximilians University, Munich, Germany (G.F.H., D.B., H.K.M., M.L., G.J., N.W.), and Department of Neurology, The Cleveland Clinic Foundation, Cleveland, Ohio (M.D., D.W.K.). * To whom correspondence should be addressed. E-mail: hamann{at}brain.nefo.med.uni-muenchen.de.
Background and Purpose--Microvascular basal lamina damage occurs after cerebral ischemia and is important for the development of hemorrhage. The aim of this study was to determine whether hypothermia could maintain microvascular integrity in ischemic stroke. Methods--Using the suture model, we subjected 12 rats to 3 hours of focal ischemia and 24 hours of reperfusion. Six rats received postischemic normothermia (37°C) and 6 received hypothermia (32°C to 34°C) for the reperfusion period; a group of 6 sham-operated animals without ischemia was used as control. Collagen type IV and hemoglobin were measured by Western blot analysis, matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography, and urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) by plasminogen-casein zymography. Results--Hypothermia reduced basal lamina collagen type IV loss: 87±16% (hypothermia) versus 43±4% (normothermia) in basal ganglia and 74±16% versus 64±4% in cortex; hypothermia reduced hemorrhage from 431±65% (normothermia) to 241±28% (basal ganglia) (P<0.05). Hypothermia also reduced MMP-2, MMP-9, uPA, and tPA (basal ganglia: MMP-2: 71±20% [hypothermia] versus 109±3% [normothermia]; MMP-9: 38±12% versus 115±4%; uPA activity: 310±86% versus 1019±22%; tPA activity: 61±17% versus 111±13%; cortex: MMP-2: 53±6% versus 116±1%; MMP-9: 16±4% versus 123±3%; uPA: 180±27% versus 176±10%; tPA: 91±15% versus 101±8%; each difference: P<0.001) (nonischemic control side=100%). Conclusions--Hypothermia maintains microvascular integrity and reduces hemorrhage and the activities of MMP-2, MMP-9, uPA, and tPA.
Accepted on November 6, 2003
Mild to Moderate Hypothermia Prevents Microvascular Basal Lamina Antigen Loss in Experimental Focal Cerebral Ischemia
Gerhard F. Hamann MD*;
Key words: basement membrane • cerebral ischemia • hypothermia • metalloproteinases • microcirculation • plasminogen activators • tissue plasminogen activator
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