机构:[1]Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China,神经科系统神经内科首都医科大学宣武医院[2]Beijing Geriatric Medical Research Center and Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China,[3]Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China,[4]Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, China
Objective By exploring the effects of miR-29a-5p knockout on neurological damage after acute ischemic stroke, we aim to deepen understanding of the molecular mechanisms of post-ischemic injury and thus provide new ideas for the treatment of ischemic brain injury. Methods miR-29a-5p knockout rats and wild-type SD rats were subjected to transient middle cerebral artery occlusion (MCAO). miR-29a levels in plasma, cortex, and basal ganglia of ischemic rats, and in plasma and neutrophils of ischemic stroke patients, as well as hypoxic glial cells were detected by real-time PCR. The infarct volume was detected by TTC staining and the activation of astrocytes and microglia was detected by western blotting. Results The expression of miR-29a-5p was decreased in parallel in blood and brain tissue of rat MCAO models. Besides, miR-29a-5p levels were reduced in the peripheral blood of acute stroke patients. Knockout of miR-29a enhanced infarct volume of the MCAO rat model, and miR-29a knockout showed M1 polarization of microglia in the MCAO rat brain. miR-29a knockout in rats after MCAO promoted astrocyte proliferation and increased glutamate release. Conclusion Knockout of miR-29a in rats promoted M1 microglial polarization and increased glutamate release, thereby aggravating neurological damage in experimental stroke rat models.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81771413, 82001268, 81771412]; Beijing Natural Science Foundation ProgramBeijing Natural Science Foundation; Scientific Research Key Program of the Beijing Municipal Commission of Education [KZ201810025041]; Xuanwu Hospital Science Program for Fostering Young Scholars [QNPY2020005]; CAMS Innovation Fund for Medical Sciences (CIFMS) [2017-I2M-3-015]
第一作者机构:[1]Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China,[2]Beijing Geriatric Medical Research Center and Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China,
共同第一作者:
通讯作者:
通讯机构:[1]Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China,[2]Beijing Geriatric Medical Research Center and Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China,[3]Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China,[4]Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, China
推荐引用方式(GB/T 7714):
Zhao Fangfang,Zhao Haiping,Fan Junfen,et al.MiR-29a Knockout Aggravates Neurological Damage by Pre-polarizing M1 Microglia in Experimental Rat Models of Acute Stroke[J].FRONTIERS IN GENETICS.2021,12:doi:10.3389/fgene.2021.642079.
APA:
Zhao, Fangfang,Zhao, Haiping,Fan, Junfen,Wang, Rongliang,Han, Ziping...&Ma, Yuanwu.(2021).MiR-29a Knockout Aggravates Neurological Damage by Pre-polarizing M1 Microglia in Experimental Rat Models of Acute Stroke.FRONTIERS IN GENETICS,12,
MLA:
Zhao, Fangfang,et al."MiR-29a Knockout Aggravates Neurological Damage by Pre-polarizing M1 Microglia in Experimental Rat Models of Acute Stroke".FRONTIERS IN GENETICS 12.(2021)