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


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.
Ishikawa
Mami
M
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA.
Vowinkel
Thorsten
T
Stokes
Karen Y
KY
Arumugam
Thiruma V
TV
Yilmaz
Gokhan
G
Nanda
Anil
A
Granger
D Neil
DN
D000818:Animals; D001921:Brain / Q000098:blood supply*; D019013:CD40 Antigens / Q000378:metabolism* / Q000502:physiology; D023201:CD40 Ligand / Q000378:metabolism* / Q000502:physiology; D002196:Capillaries / Q000473:pathology / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D007249:Inflammation / Q000209:etiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018715:Microscopy, Video; D015427:Reperfusion Injury / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction; D020521:Stroke / Q000209:etiology; D019851:Thrombophilia / Q000097:blood / Q000209:etiology
D019013:CD40 Antigens; D023201:CD40 Ligand