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HYDROGEN GAS REDUCED ACUTE HYPERGLYCEMIA-ENHANCED

HEMORRHAGIC TRANSFORMATION IN A FOCAL ISCHEMIA RAT MODEL

C. H. CHEN,a,b M. ANATOL,a Y. ZHAN,a,c W. W. LIU,a R. P. OSTROWKI,a J. TANGa AND J. H. ZHANGa,d,e*

aDepartment of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA

bDepartment of Anatomy and Embryology, Peking University Health Science Center, Beijing, PR China

cDepartment of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China

dDepartment of Neurosurgery, Loma Linda University, Loma Linda, CA, USA

eDepartment of Anesthesiology, Loma Linda University, Loma Linda, CA, USA

Neuroscience xx (2010) xxx

Abstract—Hyperglycemia is one of the major factors for hemorrhagic transformation after ischemic stroke. In this study, we tested hydrogen gas on hemorrhagic transformation in a rat focal cerebral ischemia model. Sprague–Dawley rats (n_72) were divided into the following groups: sham; sham treated with hydrogen gas (H2); Middle Cerebral Artery Occlusion (MCAO); and MCAO treated with H2 (MCAO_H2). All the rats received an injection of 50% dextrose (6 ml/kg i.p.) and underwent MCAO 15 min later. Following a 90 min ischemic period, hydrogen was inhaled for 2 h during reperfusion. We measured the level of blood glucose at 0 h, 0.5 h, 4 h, and 6 h after dextrose injection. Infarct and hemorrhagic volumes, neurologic score, oxidative stress (evaluating by the level of 8 Hydroxyguanosine  (8OHG), 4-Hydroxy-2-Nonenal (HNE) and nitrotyrosine), matrix metalloproteinase (MMP)-2/MMP-9 activity were measured at 24 h after ischemia. We found that hydrogen inhalation for 2 h reduced infarct and hemorrhagic volumes and improved neurological functions. This effect of hydrogen is accompanied by a reduction of the expressions of 8OHG, HNE, nitrotyrosine and the activity of MMP-9. Furthermore, a reduction of the blood glucose level from 500_32.51 to 366_68.22 mg/dl at 4 h after dextrose injection was observed in hydrogen treated animals. However, the treatment had no significant effect on the expression of ZO-1, occluding, collagen IV or aquaporin4 (AQP4). In conclusion, hydrogen gas reduced the infarction, hemorrhagic transformation, and improved neurological functions in rat. The potential mechanisms of decreased oxidative stress and glucose levels after hydrogen treatment warrant further investigation. © 2010 Published by Elsevier Ltd on behalf of IBRO.