Targeting Smox Is Neuroprotective and Ameliorates Brain Inflammation in Cerebral Ischemia/Reperfusion Rats
Fan Jiawei, Chen Mei, Wang Xiyan, Tian Zhijie, Wang Jinwu, Fan Daogui, Zeng Jiang, Zhang Kun, Dai Xiaozhen
Journal:TOXICOLOGICAL SCIENCES
IF:4.18
DOI:10.1093/toxsci/kfy300
PMID:30576531
Published:2018-12-21
research field:神经科学分子生物学药理学干细胞生物学遗传学与基因组学生物化学
Abstract
Spermine oxidase (Smox) is a member of the polyamine oxidases and has been demonstrated to be involved in ischemic brain damage. In this study, we found that Smox expression was increased in a rat middle cerebral artery occlusion (MCAO) model and in cultured primary neurons after oxygen-glucose deprivation and reoxygenation (OGD/R). Smox downregulation by the adeno-associated virus RNA interference system significantly reduced the MCAO-induced brain infarct volume and neurological deficits and decreased neuronal apoptosis and inflammatory reactions. In addition, significant microglial activation and increased IL-6 and TNF-α expression were observed in microglia treated with supernatant from neurons after OGD/R. However, a significant reduction in microglial activation as well as IL-6 and TNF-α expression was observed in microglia treated with supernatant from Smox downregulated neurons after OGD/R. Therefore, the results indicated that Smox is an important mediator of cerebral ischemia injury and may be a therapeutic target for cerebral ischemia patients.
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