MiR-29a Knockout Aggravates Neurological Damage by Pre-polarizing M1 Microglia in Experimental Rat Models of Acute Stroke

Fangfang Zhao; Haiping Zhao; Junfen Fan; Rongliang Wang; Ziping Han; Zhen Tao; Yangmin Zheng; Feng Yan; Yuyou Huang; Lei Yu; Xu Zhang; Xiaolong Qi; Lianfeng Zhang; Yumin Luo; Yuanwu Ma

doi:10.3389/fgene.2021.642079

MiR-29a Knockout Aggravates Neurological Damage by Pre-polarizing M1 Microglia in Experimental Rat Models of Acute Stroke

Front Genet. 2021 Mar 15:12:642079. doi: 10.3389/fgene.2021.642079. eCollection 2021.

Authors

Fangfang Zhao^{1

2}, Haiping Zhao^{1

2}, Junfen Fan^{1

2}, Rongliang Wang^{1

2}, Ziping Han^{1

2}, Zhen Tao^{1

2}, Yangmin Zheng^{1

2}, Feng Yan^{1

2}, Yuyou Huang^{1

2}, Lei Yu^{3

4}, Xu Zhang^{3

4}, Xiaolong Qi^{3

4}, Lianfeng Zhang^{3

4}, Yumin Luo^{1

2}, Yuanwu Ma^{3

4}

Affiliations

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.

Abstract

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.

Keywords: Ischemic stroke; astrocyte; glutamate; miR-29a; microglia.