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

Ishikawa, Mami, Vowinkel, Thorsten, Stokes, Karen Y., Arumugam, Thiruma V., Yilmaz, Gokhan, Nanda, Anil and Granger, D. Neil (2005) CD40/CD40 ligand signaling in mouse cerebral microvasculature after focal ischemia/reperfusion. Circulation, 111 13: 1690-1696. doi:10.1161/01.CIR.0000160349.42665.0C


Author Ishikawa, Mami
Vowinkel, Thorsten
Stokes, Karen Y.
Arumugam, Thiruma V.
Yilmaz, Gokhan
Nanda, Anil
Granger, D. Neil
Title CD40/CD40 ligand signaling in mouse cerebral microvasculature after focal ischemia/reperfusion
Journal name Circulation   Check publisher's open access policy
ISSN 0009-7322
1524-4539
Publication date 2005-04
Sub-type Article (original research)
DOI 10.1161/01.CIR.0000160349.42665.0C
Volume 111
Issue 13
Start page 1690
End page 1696
Total pages 7
Place of publication Baltimore, MD, US.A.
Publisher Lippincott Williams & Wilkins
Language eng
Subject C1
1103 Clinical Sciences
Formatted abstract
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.

© American Heart Association 2005
Keyword Platelets
Leukocytes
Cerebral ischemia
Microcirculation
Stroke
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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Created: Tue, 17 Nov 2009, 12:21:47 EST