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Ischemic Preconditioning Induces Oligodendrogenesis in Mouse Brain: Effects of Nrf2 Deficiency

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Abstract

Ischemic preconditioning (IPC) is an approach of protection against cerebral ischemia by inducing endogenous cytoprotective machinery. However, few studies in neurogenesis and oligodendrogenesis after IPC have been reported, especially the latter. The purpose of this study is to test our hypothesis that IPC may also induce cell proliferation and oligodendrogenesis in the subventricular zone and striatum, as well as to investigate the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) on oligodendrogenesis. IPC was induced in mice by 12-min ischemia through the occlusion of the middle cerebral artery. Newly generated cells were labeled with 5-bromo-2′-deoxyuridine. Our findings demonstrated that IPC stimulated the proliferation of neural stem cells in the subventricular zone, promoted the generation of oligodendrocyte precursor cells in the striatum and corpus callosum/external capsule (CC/EC), and stimulated oligodendrocyte precursor cells differentiation into oligodendrocytes in the striatum and the CC/EC. Furthermore, we describe a crucial role for Nrf2 in IPC-induced oligodendrogenesis in the subventricular zone, striatum, and CC/EC and show for the first time that Nrf2 promoted the migration and differentiation of oligodendrocyte precursor cells into oligodendrocytes in the striatum and CC/EC. Our data imply that IPC stimulates the oligodendrogenesis in the brain and that Nrf2 signaling may contribute to the oligodendrogenesis.

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Acknowledgements

This work was supported by the American Heart Association under the Award Number 2560122 and internal funds from the PIBDR and Department of Neurology of the University of Pittsburgh to F.Z. Qianqian Li was a student at Zhengzhou University and a visiting research scholar at the University of Pittsburgh (from August 2017 to January 2019). The authors thank Pat Strickler and Samantha DiSalvio for their administrative support.

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Authors and Affiliations

  1. Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

    Qianqian Li & Jiyu Lou

  2. Department of Neurology, Pittsburgh Institute of Brain Disorders and Recovery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Qianqian Li, Tuo Yang, Zhishuo Wei, Senmiao Li & Feng Zhang

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  1. Qianqian Li
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  2. Jiyu Lou
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  3. Tuo Yang
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  4. Zhishuo Wei
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  5. Senmiao Li
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  6. Feng Zhang
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Contributions

QL, TY, JL, and FZ designed the study. QL, ZW, and SL carried out experiments. QL and TY analyzed the data. QL, TY, JL, and FZ prepared the manuscript. All the authors read and approved the final manuscript.

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Correspondence to Feng Zhang.

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Li, Q., Lou, J., Yang, T. et al. Ischemic Preconditioning Induces Oligodendrogenesis in Mouse Brain: Effects of Nrf2 Deficiency. Cell Mol Neurobiol 42, 1859–1873 (2022). https://doi.org/10.1007/s10571-021-01068-5

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