Normobaric oxygen inhibits AQP4 and NHE1 expression in experimental focal ischemic stroke

• Published in: International journal of molecular medicine 2019-03, Vol.43 (3), p.1193-1202
• Main Authors: Yang, Dongbin, Ma, Liyan, Wang, Peng, Yang, Dongjing, Zhang, Yingna, Zhao, Xue, Lv, Jie, Zhang, Jing, Zhang, Zhenxiang, Gao, Feng
• Format: Article
• Language: English
• Subjects: Aquaporins; Brain; Care and treatment; Carotid arteries; Cerebral edema; Cerebral ischemia; Development and progression; Drinking water; Edema; Ethanol; Gene expression; Genetic aspects; Health aspects; Hypoxia; Ischemia; Messenger RNA; Oxygen therapy; Pathogenesis; Polymerase chain reaction; Protein expression; Reperfusion injury; RNA; Rodents; Stroke; Studies; Surgery; Transport proteins; Veins & arteries; Water
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2018.4037

The aim of the present study was to determine the effect of 60% normobaric oxygen (NBO) on neurological function, brain edema and the expression of hypoxia-inducible factor-l[alpha] (HIF-1[alpha]), aquaporin 4 (AQP4) and [Na.sup.+]/[H.sup.+] exchanger 1 (NHE1) in a rat model of cerebral ischemia-reperfusion injury. Male Sprague-Dawley rats underwent transient focal cerebral ischemia via right middle cerebral artery occlusion (MCAO) for 120 min followed by 48 h of reperfusion. The rats were exposed to NBO at 60 and 100% or no treatment during reperfusion for 48 h. Neurological impairment score (NIS) was evaluated prior to the sacrifice of all rats. Hematoxylin-eosin staining was performed after 48 h of reperfusion with NBO treatment. The infarct volume and brain water content (BWC) were determined to assess brain ischemic injury at 24 and 48 h. The levels of HIF-1[alpha], AQP4 and NHE1 expression in brain tissue samples were determined by western blotting and reverse transcription-quantitative polymerase chain reaction analysis. During reperfusion, the protein and mRNA expression of HIF-1[alpha], AQP4 and NHE1 increased over time (up to 48 h). Exposure to 60 and 100% NBO during reperfusion following MCAO improved NIS, and alleviated BWC and infarct volume after 24 and 48 h, with further improvements in the 100% NBO group, compared with 60%. Additionally, the molecular mechanisms involved in the effects of NBO may be associated with reduced AQP4 and NHE1 expression and increased HIF-1[alpha] expression. However, 60% NBO therapy during reperfusion following an acute ischemic stroke did not achieve the same effects as 100% NBO. Further experimental studies should be performed to elucidate the mechanism and beneficial effects of 60% NBO, as it is more cost-effective to use, compared with 100% NBO.