Original Article

Journal of Cerebral Blood Flow & Metabolism (2004) 24, 668–676; doi:10.1097/01.WCB.0000117812.35136.5B

Leukocyte-Endothelium Interactions During Permanent Focal Cerebral Ischemia in Mice

Supported by a grant from the Uehara Memorial Foundation (to HK) and by the DFG Graduiertenkolleg "Neurotraumatologie und Neuro-psychologische Rehabilitation" GK688 (to SWK).

Hiroharu Kataoka, Seong-Woong Kim and Nikolaus Plesnila

From the Institute for Surgical Research, Ludwig-Maximilians-University, Munich, Germany.

Correspondence: Nikolaus Plesnila, Institute for Surgical Research, Ludwig-Maximilians-University, Marchioninistr.15, D-81377, Munich, Germany; e-mail: plesnila@icf.med.uni-muenchen.de.

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Abstract

The contribution of leukocyte infiltration to brain damage after permanent focal cerebral ischemia and the underlying molecular mechanisms are still unclear. Therefore, the aim of this study was to establish a mouse model for the visualization of leukocytes in the cerebral microcirculation in vivo and to investigate leukocyte-endothelial interaction (LEI) after permanent middle cerebral artery occlusion (MCAO). Sham-operated 129/Sv mice showed physiologic LEI in pial venules as observed by intravital fluorescent microscopy. Permanent focal cerebral ischemia induced a significant increase of LEI predominantly in pial venules. The number of rolling and adherent leukocytes reached 36.5 plusminus 13.2/100 mum times min and 22.5 plusminus 7.9/100 mum times min, respectively at 120 minutes after MCAO (P = 0.016 vs. control). Of note, rolling and adherent leukocytes were also observed in arterioles of ischemic animals (7.3 plusminus 3.0/100 mum times min rolling and 3.0 plusminus 3.6/100 mum times min adherent). Capillary density was not different between groups. These results demonstrate that leukocytes accumulate in the brain not only after transient but also after permanent focal cerebral ischemia and may therefore contribute to brain damage after stroke without reperfusion.

Keywords:

Leukocytes, Microcirculation, Middle cerebral artery occlusion, Permanent cerebral ischemia, Mice

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