Shi Yan, Tian Tian, Cai Er-Li, Yang Can, Yang Xin
Faculty of Laboratory Medicine, School of Medicine, Hunan Normal University, Changsha, China.
The Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Front Neurosci. 2021 Mar 26;15:649982. doi: 10.3389/fnins.2021.649982. eCollection 2021.
Ischemic stroke induces neuronal cell death and causes brain dysfunction. Preventing neuronal cell death after stroke is key to protecting the brain from stroke damage. Nevertheless, preventative measures and treatment strategies for stroke damage are scarce. Emerging evidence suggests that microRNAs (miRNAs) play critical roles in the pathogenesis of central nervous system (CNS) disorders and may serve as potential therapeutic targets.
A photochemically induced thrombosis (PIT) mouse model was used as an ischemic stroke model. qRT-PCR was employed to assess changes in miRNAs in ischemic lesions of PIT-stroke mice and primary cultured neurons subjected to oxygen-glucose deprivation (OGD). 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed to evaluate brain infarction tissues . TUNEL staining was employed to assess neuronal death . Neurological scores and motor coordination were investigated to evaluate stroke damage, including neurological deficits and motor function.
and results demonstrated that levels of miR-124 were significantly decreased following stroke, whereas changes in death-associated protein kinase 1 (DAPK1) levels exhibited the converse pattern. DAPK1 was identified as a direct target of miR-124. N-methyl-D-aspartate (NMDA) and OGD-induced neuronal death was rescued by miR-124 overexpression. Upregulation of miR-124 levels significantly improved PIT-stroke damage, including the overall neurological function in mice.
We demonstrate the involvement of the miR-124/DAPK1 pathway in ischemic neuronal death. Our results highlight the therapeutic potential of targeting this pathway for ischemic stroke.
缺血性中风会导致神经元细胞死亡并引起脑功能障碍。预防中风后的神经元细胞死亡是保护大脑免受中风损伤的关键。然而，针对中风损伤的预防措施和治疗策略却很匮乏。新出现的证据表明，微小RNA（miRNA）在中枢神经系统（CNS）疾病的发病机制中起关键作用，可能成为潜在的治疗靶点。
采用光化学诱导血栓形成（PIT）小鼠模型作为缺血性中风模型。运用qRT-PCR评估PIT中风小鼠缺血性损伤部位及原代培养的神经元在氧糖剥夺（OGD）情况下miRNA的变化。进行2,3,5-三苯基氯化四氮唑（TTC）染色以评估脑梗死组织。采用TUNEL染色评估神经元死亡情况。研究神经学评分和运动协调性以评估中风损伤，包括神经功能缺损和运动功能。
结果表明，中风后miR-124水平显著降低，而死亡相关蛋白激酶1（DAPK1）水平的变化则呈现相反模式。DAPK1被确定为miR-124的直接靶点。miR-124过表达可挽救N-甲基-D-天冬氨酸（NMDA）和OGD诱导的神经元死亡。miR-124水平上调显著改善了PIT中风损伤，包括小鼠的整体神经功能。
我们证明了miR-124/DAPK1通路参与缺血性神经元死亡。我们的结果突出了针对该通路治疗缺血性中风的潜力。
