CD44 deficiency in mice protects brain from cerebral ischemia injury.
CD44 is a transmembrane glycoprotein known to be involved in endothelial cell recognition, lymphocyte trafficking, and regulation of cytokine gene expression in inflammatory diseases. In the present study, we demonstrated that the expression of CD44 mRNA was induced in a mouse model of cerebral ischemia. A potential role of CD44 in ischemic brain injury was investigated using CD44-deficient (CD44-/-) mice. Over 50% (p < 0.05, n = 14) and 78% (p < 0.05, n = 10) reduction in ischemic infarct was observed in CD44-/- mice compared with that of wild-type mice following transient (30 min ischemia) and permanent (24 h) occlusion of the middle cerebral artery (MCAO), respectively. Similarly, significant improvement was observed in neurological function in CD44-/- mice as evidenced by spontaneous and forced motor task scores. The marked protection from ischemic brain injury in CD44-/- mice was associated with normal physiological parameters, cytokine gene expression, astrocyte and microglia activation as compared with wild-type mice. However, in CD44-/- mice, significantly lower expression of soluble interleukin-1beta protein was noted after brain ischemia. Our data provide new evidence on the potential role of CD44 in brain tissue in response to ischemia and may suggest that this effect might be associated with selective reduction in inflammatory cytokines such as interleukin-1beta.
Wang
Xinkang
X
Departments of Cardiovascular Sciences and Neurosciences, Bristol-Myers Squibb Company, Wilmington, Delaware 19880-0400, USA. xinkang.wang@bms.com
Xu
Lin
L
Wang
Hugh
H
Zhan
Yutian
Y
Puré
Ellen
E
Feuerstein
Giora Z
GZ
D000818:Animals; D001522:Behavior, Animal; D001794:Blood Pressure; D001921:Brain / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D018450:Disease Progression; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009043:Motor Activity; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D018960:Hyaluronan Receptors; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha