Jiaming Zhang1, Kai Wang2, Jia Qi3, Xiaodong Cao1, Feng Wang4. 1. Department of Emergency, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, China 214023. 2. Department of Neurology, Second Affiliated Hospital of Xuzhou Medical University, Xuzhou City, Jiangsu Province, China. 3. Department of Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China. 4. Department of Neurology, Shanghai 7th Hospital Affiliated to Shanghai Traditional Chinese Medical University, Shanghai, China 200000.
Abstract
INTRODUCTION: Hemorrhagic transformation (HT) is one of the most common complications of ischemic stroke which is exacerbated by hyperglycemia. Oxidative stress, inflammatory response, and matrix metalloproteinases (MMPs) have been evidenced to play a vital role in the pathophysiology of HT. Our previous study has reported that 17-DMAG, an Hsp90 inhibitor, protects the brain against ischemic injury via inhibiting inflammation and reducing MMP-9 after ischemia. However, whether 17-DMAG would attenuate HT in hyperglycemic middle cerebral artery occlusion (MCAO) rats is still unknown. METHODS: Acute hyperglycemia was induced by an injection of 50% dextrose. Rats were pretreated with 17-DMAG before MCAO. Infarction volume, hemorrhagic volume neurological scores, expressions of inflammatory molecules and tight junction proteins, and activity of MMP-2 and MMP-9 were assessed 24 h after MCAO. RESULTS: 17-DMAG was found to reduce HT, improve neurological function, and inhibit expressions of inflammatory molecules and the activation of MMPs at 24 h after MCAO. CONCLUSION: These results implicated that Hsp90 could be a novel therapeutic target in HT following ischemic stroke.
INTRODUCTION: Hemorrhagic transformation (HT) is one of the most common complications of ischemic stroke which is exacerbated by hyperglycemia. Oxidative stress, inflammatory response, and matrix metalloproteinases (MMPs) have been evidenced to play a vital role in the pathophysiology of HT. Our previous study has reported that 17-DMAG, an Hsp90 inhibitor, protects the brain against ischemic injury via inhibiting inflammation and reducing MMP-9 after ischemia. However, whether 17-DMAG would attenuate HT in hyperglycemic middle cerebral artery occlusion (MCAO) rats is still unknown. METHODS: Acute hyperglycemia was induced by an injection of 50% dextrose. Rats were pretreated with 17-DMAG before MCAO. Infarction volume, hemorrhagic volume neurological scores, expressions of inflammatory molecules and tight junction proteins, and activity of MMP-2 and MMP-9 were assessed 24 h after MCAO. RESULTS: 17-DMAG was found to reduce HT, improve neurological function, and inhibit expressions of inflammatory molecules and the activation of MMPs at 24 h after MCAO. CONCLUSION: These results implicated that Hsp90 could be a novel therapeutic target in HT following ischemic stroke.
Authors: Yi-Xin Wang; Baby Martin-McNulty; Valdeci da Cunha; Jon Vincelette; Xiangru Lu; Qingping Feng; Meredith Halks-Miller; Mithra Mahmoudi; Miriam Schroeder; Babu Subramanyam; Jih-Lie Tseng; Gary D Deng; Sabine Schirm; Anthony Johns; Katalin Kauser; William P Dole; David R Light Journal: Circulation Date: 2005-04-25 Impact factor: 29.690