Hydrogen gas reduced acute hyperglycemia-enhanced hemorrhagic transformation in a focal ischemia rat model

• Published in: Neuroscience Vol. 169; no. 1; pp. 402 - 414
• Main Authors: Chen, C.H, Manaenko, A, Zhan, Y, Liu, W.W, Ostrowki, R.P, Tang, J, Zhang, J.H
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 11.08.2010; Elsevier
• Subjects: Administration, Inhalation; Aldehydes - analysis; Animals; Antioxidants - administration & dosage; Antioxidants - therapeutic use; Aquaporin 4 - biosynthesis; Aquaporin 4 - genetics; Biological and medical sciences; Brain Damage, Chronic - prevention & control; Cerebral Hemorrhage - blood; Cerebral Hemorrhage - etiology; Cerebral Hemorrhage - prevention & control; Disease Progression; Drug Evaluation, Preclinical; Extracellular Matrix Proteins - analysis; Fundamental and applied biological sciences. Psychology; Glucose - toxicity; hydrogen; Hydrogen - administration & dosage; Hydrogen - therapeutic use; hyperglycemia; Hyperglycemia - chemically induced; Hyperglycemia - complications; Infarction, Middle Cerebral Artery - blood; Infarction, Middle Cerebral Artery - complications; Infarction, Middle Cerebral Artery - drug therapy; Male; Matrix Metalloproteinase 2 - analysis; Matrix Metalloproteinase 9 - analysis; MCAO; Neurology; neuroprotection; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - therapeutic use; Random Allocation; Rats; Rats, Sprague-Dawley; Tyrosine - analogs & derivatives; Tyrosine - analysis; Vertebrates: nervous system and sense organs; MCAO; PBS; phosphate buffered solution; TTC; BBB; aquaporin4; MMPs; 2, 3, 5-triphenyltetrazolium chloride; AQP4; hydrogen; 8OHG; hyperglycemia; FITC; blood–brain barrier; tetramethylrhodamine isothiocyanate; neuroprotection; 4-Hydroxy-2-Nonenal; 8 Hydroxyguanosine; TRITC; fluorescein isothiocyanate; matrix metalloproteinases; HNE; middle cerebral artery occlusion; Animal model; Neuroprotection; Vertebrata; Hyperglycemia; Mammalia; Rat; Acute; Animal; Rodentia
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2010.04.043

Abstract Hyperglycemia is one of the major factors for hemorrhagic transformation after ischemic stroke. In this study, we tested the effect of 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 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 (evaluated by measuring the level of 8 Hydroxyguanosine (8OHG), 4-Hydroxy-2-Nonenal (HNE) and nitrotyrosine), and 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 was accompanied by a reduction of the expression of 8OHG, HNE, and 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, occludin, collagen IV or aquaporin4 (AQP4). In conclusion, hydrogen gas reduced brain infarction, hemorrhagic transformation, and improved neurological function in rats. The potential mechanisms of decreased oxidative stress and glucose levels after hydrogen treatment warrant further investigation.