Background Neonatal hypoxic-ischemic encephalopathy (HIE) represents as a major cause of neonatal morbidity and mortality. However, the underlying molecular mechanisms in brain damage are still not fully elucidated. This study was conducted to determine the specific potential molecular mechanism in the hypoxic-ischemic induced cerebral injury. Methods Here, hypoxic-ischemic (HI) animal models were established and primary cortical neurons were subjected to oxygen–glucose deprivation (OGD) to mimic HIE model in vivo and in vitro. The HI-induced neurological injury was evaluated by Zea-longa scores, Triphenyte-trazoliumchloride (TTC) staining the Terminal Deoxynucleotidyl Transferased Utp Nick End Labeling (TUNEL) and immunofluorescent staining. Then the expression of Cytochrome c oxidase subunit 5a (COX5A) was determined by immunohistochemistry, western blotting (WB) and quantitative real time Polymerase Chain Reaction (qRT-PCR) techniques. Moreover, HSV-mediated COX5A over-expression virus was transducted into OGD neurons to explore the role of COX5A in vitro, and the underlying mechanism was predicted by GeneMANIA, then verified by WB and qRT-PCR. Results HI induced a severe neurological dysfunction, brain infarction, and cell apoptosis as well as obvious neuron loss in neonatal rats, in corresponding to the decrease on the expression of COX5A in both sides of the brain. What’s more, COX5A over-expression significantly promoted the neuronal survival, reduced the apoptosis rate, and markedly increased the neurites length after OGD. Moreover, Triosephosephate isomerase (TPI) was predicted as physical interactions with COX5A, and COX5A over-expression largely increased the expressional level of TPI. Conclusions The present findings suggest that COX5A plays an important role in promoting neurological recovery after HI, and this process is related to TPI up-regulation.

中文翻译：

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COX5A 过表达可保护新生大鼠皮层神经元免受与 TPI 上调相关的缺氧缺血性损伤

背景新生儿缺氧缺血性脑病（HIE）是新生儿发病和死亡的主要原因。然而，脑损伤的潜在分子机制仍未完全阐明。本研究旨在确定缺氧缺血性脑损伤的具体潜在分子机制。方法 建立缺氧缺血（HI）动物模型，并对原代皮层神经元进行氧糖剥夺（OGD）以模拟体内和体外 HIE 模型。通过玉米评分、氯化三苯四氮唑 (TTC) 染色、末端脱氧核苷酸转移 Utp 缺口末端标记 (TUNEL) 和免疫荧光染色来评估 HI 诱导的神经损伤。然后通过免疫组织化学、蛋白质印迹（WB）和定量实时聚合酶链反应（qRT-PCR）技术测定细胞色素c氧化酶亚基5a（COX5A）的表达。此外，将HSV介导的COX5A过表达病毒转导至OGD神经元中以探索COX5A在体外的作用，并通过GeneMANIA预测其潜在机制，然后通过WB和qRT-PCR进行验证。结果HI引起新生大鼠严重的神经功能障碍、脑梗塞、细胞凋亡以及明显的神经元丢失，与两侧大脑COX5A表达的减少相对应。此外，COX5A过表达显着促进OGD后神经元存活，降低凋亡率，并显着增加神经突长度。此外，磷酸三糖异构酶（TPI）被预测为与COX5A的物理相互作用，并且COX5A的过表达很大程度上增加了TPI的表达水平。结论本研究结果提示COX5A在促进HI后神经功能恢复中发挥重要作用，该过程与TPI上调有关。