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Macrophage Nuclear Receptor Corepressor 1 Deficiency Protects Against Ischemic Stroke in Mice

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Abstract

Microglia/macrophage activation plays an essential role in Ischemic stroke (IS). Nuclear receptor corepressor 1 (NCoR1) has been identified as a vital regulator in macrophages. The present study aims to explore the functions of macrophage NCoR1 in IS. Macrophage NCoR1 knockout (MNKO) mice and littermate control mice were subjected to middle cerebral artery occlusion (MCAO). Our data showed that macrophage NCoR1 deficiency significantly reduced the infarct size and infarct volume as well as brain edema after MCAO. Additionally, MNKO induced less microglia/macrophage infiltration and activation, neuroinflammation, apoptosis of neuronal cells, and BBB disruption in brains after IS. Mechanistic studies revealed that NCoR1 interacted with LXRβ in microglia and MNKO impaired the activation of the Nuclear factor-κB signaling pathway in brains after IS. Our data demonstrated that macrophage NCoR1 deficiency inhibited microglia/macrophage activation and protected against IS. Targeting NCoR1 in microglia/macrophage may be a potential approach for IS treatment.

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Abbreviations

CNS:

Central nervous system

IS:

Ischemic stroke

MCAO:

Middle cerebral artery occlusion

NCoR1:

Nuclear receptor corepressor1

MNKO:

Macrophage NCoR1 knockout

LC:

Littermate control

TTC:

Triphenyl tetrazolium chloride

Iba-1:

Ionized calcium binding adaptor molecule-1

Tunnel:

Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling

BBB:

Blood-brain barrier

MMP-9:

Matrix metalloprotein-9

ZO-1:

Zonula occludens 1

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Funding

This work was supported by grants from the National Natural Science Foundation of China (81971093, 81725003, 31900810, 81900227), Science and Technology Commission of Shanghai Municipal (21ZR1439000), and Innovative Research Team of High-Level Local Universities in Shanghai.

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Author notes

  1. Shuai Shao and Yanlin Chen and Linjuan Du contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Shuai Shao, Yan-Lin Chen, Xiao-Hua Zhang & Feng Jia

  2. Laboratory of Oral Microbiota and Systemic Diseases, College of Stomatology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Lin-Juan Du, Yuan Liu, Hong Zhu, Lu-Jun Zhou, Ting Liu, Wen-Zhen Lin, Fei Yu, Xiao-Xin Ma, Xue-Rui Shi, Xiao-Qian Meng, Yan Liu, Yong-Li Wang, Lan Bai & Sheng-Zhong Duan

  3. National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology &, Shanghai Research Institute of Stomatology, Shanghai, China

    Lin-Juan Du, Yuan Liu, Hong Zhu, Lu-Jun Zhou, Ting Liu, Wen-Zhen Lin, Fei Yu, Xiao-Xin Ma, Xue-Rui Shi, Xiao-Qian Meng, Yan Liu, Yong-Li Wang, Lan Bai & Sheng-Zhong Duan

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  1. Shuai Shao
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Correspondence to Xiao-Hua Zhang.

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Shao, S., Chen, YL., Du, LJ. et al. Macrophage Nuclear Receptor Corepressor 1 Deficiency Protects Against Ischemic Stroke in Mice. J. of Cardiovasc. Trans. Res. 15, 816–827 (2022). https://doi.org/10.1007/s12265-021-10187-9

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