CD40/CD40 ligand signaling in mouse cerebral microvasculature after focal ischemia/reperfusion

Article

关键词: ENDOTHELIAL GROWTH-FACTOR;    BLOOD-BRAIN-BARRIER;    CD40 LIGAND;    P-SELECTIN;    MURINE STROKE;    PLATELET ACTIVATION;    ARTERY OCCLUSION;    CELL-ADHESION;    EXPRESSION;    ISCHEMIA;   

DOI  :  10.1161/01.CIR.0000160349.42665.0C

来源: SCIE

【 摘 要 】

Background - CD40/CD40 ligand (CD40L) signaling contributes to proinflammatory and prothrombogenic responses in the vasculature. CD40/CD40L expression is elevated in patients after a transient ischemic attack or stroke. The purpose of this study was to investigate the role of CD40/CD40L signaling in cerebral microvascular dysfunction and tissue injury response to middle cerebral artery occlusion (MCAO) and reperfusion. Methods and Results - Intravital fluorescence microscopy was used to visualize the cerebral microcirculation of wild-type (WT), CD40-deficient, and CD40L-deficient mice subjected to 1-hour MCAO and 4-hour reperfusion. The adhesion of platelets and of leukocytes and vascular permeability were measured in postcapillary venules after 4-hour and 1-hour reperfusions, respectively. Cerebral infarct volume was analyzed 24 hours after reperfusion. Platelet and leukocyte adhesion was elevated and blood/brain barrier function was compromised by MCAO in WT mice. Blood cell recruitment and increased permeability were blunted in both CD40-deficient and CD40L-deficient mice. Infarct volume was also reduced in CD40- and CD40L-deficient mice compared with WT mice. Conclusions - Our findings indicate that CD40/CD40L signaling contributes to inflammatory and prothrombogenic responses and brain infarction induced by MCAO and reperfusion. The CD40/CD40L dyad may play a significant pathogenic role in the acute phase of ischemic stroke.

【 授权许可】

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