Department of Anesthesiology, Department of Neurology, The Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, China.
Department of Anesthesiology, Sun Yat‑Sen Memorial Hospital, Sun Yat‑Sen University, Guangdong, 510120, China.
Brain Res Bull. 2020 Sep;162:218-230. doi: 10.1016/j.brainresbull.2020.06.011. Epub 2020 Jun 21.
Neonatal hypoxic-ischemic encephalopathy (HIE) is major cause of neonatal death or long-term neurodevelopmental disabilities, which becomes a major practical problem currently in clinic. Whereas, its pathophysiology and underlying molecular mechanism is not clear. MicroRNAs are involved in the normal growth and development of neuronal cells. Herein, the objective of this research was to examine the roles of miR-410-3p in neurological deficits, neuronal injury and neuron apoptosis after hypoxic-ischemic and to explore its associated mechanisms. We established the hypoxic-ischemic brain damage (HIBD) model and oxygen glucose deprivation (OGD) model. Zea-longa score and TTC staining were used to detect the acute cerebral dysfunction after HIBD. QPCR verification exhibited notable downregulation of miR-410-3p expression at 24 h in rats after HIBD as well as that in PC12, SY5Y cells and primary cortical neurons post OGD. To further determine the function of miR-410-3p, lentivirus-mediated overexpression virus was applied in vivo and in vitro. Behavioral tests, including Morris water maze, open field test, Y maze test, neurological severity score and rotating rod test, were performed to evaluate long-term behavioral changes of rats at 1 month post HIBD. The results showed that the number of cells together with the axonal length were reduced post OGD. While the increase of cells number and the axonal length was measured after upregulating miR-410-3p. Meanwhile, miR-410-3p overexpression inhibited neuron apoptosis and enhanced neuronal survival. In addition, long-term motor and cognitive functions were remarkably recovered in HIBD rats with miR-410-3p overexpression. Together, miR-410-3p exerts a critical role in protecting neuronal growth as well as promoting motor and cognitive function recovery in neonatal rats subjected to HIBD. The current study therefore provides critical insights to develop the activator of miR-410-3p for the clinical treatment of HIBD in future clinic trial.
新生儿缺氧缺血性脑病（HIE）是新生儿死亡或长期神经发育障碍的主要原因，目前在临床上是一个重大的实际问题。然而，其病理生理学和潜在的分子机制尚不清楚。miRNAs 参与神经元细胞的正常生长和发育。在此，本研究旨在研究 miR-410-3p 在缺氧缺血后神经功能缺损、神经元损伤和神经元凋亡中的作用，并探讨其相关机制。我们建立了缺氧缺血性脑损伤（HIBD）模型和氧葡萄糖剥夺（OGD）模型。Zea-longa 评分和 TTC 染色用于检测 HIBD 后大鼠急性脑功能障碍。QPCR 验证显示，HIBD 后大鼠 24 小时以及 OGD 后 PC12、SY5Y 细胞和原代皮质神经元中 miR-410-3p 表达明显下调。为了进一步确定 miR-410-3p 的功能，我们在体内和体外应用了慢病毒介导的过表达病毒。Morris 水迷宫、旷场试验、Y 迷宫试验、神经功能严重程度评分和旋转棒试验等行为学试验用于评估 HIBD 后 1 个月大鼠的长期行为变化。结果显示，OGD 后细胞数量和轴突长度减少，上调 miR-410-3p 后细胞数量和轴突长度增加。同时，miR-410-3p 过表达抑制神经元凋亡，增强神经元存活。此外，miR-410-3p 过表达可显著改善 HIBD 大鼠的长期运动和认知功能。综上所述，miR-410-3p 在保护神经元生长和促进 HIBD 新生大鼠运动和认知功能恢复方面发挥着重要作用。本研究为今后临床试验中开发 miR-410-3p 的激活剂治疗 HIBD 提供了重要的见解。
