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 RACE in the ischemic hemisphere. In I 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 7 h of OGD culture. Notably, blockade of RACE 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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.