RAGE expression is up-regulated in human cerebral ischemia and pMCAO rats.
To determine whether the receptor for advanced glycation endproducts (RAGE) contributes to cerebral ischemia, we evaluated RAGE expression in human cerebral ischemia and a model of permanent middle cerebral artery occlusion (pMCAO) in rats. Biopsy specimens were obtained from 12 patients with unilateral cerebral infarction. For the pMCAO model, the middle cerebral artery (MCA) of Sprague-Dawley (SD) rats was permanently occluded. Immunohistochemistry and Western blotting were used to measure RAGE expression in the ischemic hemisphere relative to the normal hemisphere. PC12 cells subjected to oxygen and glucose deprivation (OGD) were used to evaluate the role of RAGE in cell injury. As expected, cerebral ischemia patients expressed elevated levels of RAGE in the ischemic hemisphere. In 1 and 2 days pMCAO rats, levels of RAGE were higher in the ischemic hemisphere relative to the non-ischemic hemisphere, and expression was primarily located in the penumbra of the ischemic hemisphere. In PC12 cells, levels of RAGE increased after 7h of OGD culture. Notably, blockade of RAGE with a selective RAGE antibody in vitro reduced the cytotoxicity caused by OGD. The present data suggest that RAGE is up-regulated in human cerebral ischemia and pMCAO rats, suggesting a role for RAGE in brain ischemia.
Zhai
Dong-Xu
DX
Department of Neurobiology, Heilongjiang Provincial Key Laboratory of Neurobiology, Harbin Medical University, Harbin 150081, PR China.
Kong
Qing-Fei
QF
Xu
Wang-Shu
WS
Bai
Sha-Sha
SS
Peng
Hai-Sheng
HS
Zhao
Kai
K
Li
Guo-Zhong
GZ
Wang
Dan-Dan
DD
Sun
Bo
B
Wang
Jing-Hua
JH
Wang
Guang-You
GY
Li
Hu-Lun
HL
D000328:Adult; D000368:Aged; D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology*; D002452:Cell Count; D002540:Cerebral Cortex / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology*
D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic