Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (on line): 1-6.

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Jia-Lei Yang1, 2, #, Hong Fan1, 3, #, Fan-Fan Fu1, #, Bao-Lin Guo1, Ying Huang4, Li Sun1, Wen-Ting Wang1, Jun-Ling Xing1, Xin-Tian Hu5, Yu-Qiang Ding4, Kun Zhang1, *, Ying-Zhou Hu5, *, Ya-Zhou Wang1, *   

  1. 1Department of Neurobiology and Institute of Neurosciences, School of Basic Medicine, Fourth Military Medical University, Xi’an, Shaanxi Province, China; 2China National Clinical Research Center for Neurological Diseases, Department of Neurology, Beijing Tiantan Hospital, Beijing, China; 3Department of Neurology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China; 4State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute of Brain Science, Fudan University, Shanghai, China; 5Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan Province, China
  • Online:2023-01-01 Published:2022-07-30
  • Contact: Ya-Zhou Wang, PhD, yazhouw@fmmu.edu.cn; Ying-Zhou Hu, PhD, huyingzhou@mail.kiz.ac.cn; Kun Zhang, PhD, Kunyang1028@126.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China (NSFC), Nos. 82171346 (to YZW), 82171269 (to JLY), 8171471 (to HF); Beijing Nova Program, No. Z201100006820076 (to JLY).

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Abstract: Adult cortex has long been regarded as “non-neurogenic”. Whether injury could induce neurogenesis in adult cortex is still controversial. Here, we report that focal ischemia stimulates a transient wave of local neurogenesis. By 5′-bromo-2′-deoxyuridine (BrdU)-labeling, we demonstrated a rapid generation of DCX-positive neuroblasts which died quickly in mice cerebral cortex following ischemia. Nestin-CreER-based cell ablation and fate mapping showed a small contribution of neuroblasts by SVZ neural stem cells. By adopting a mini-photothrombotic ischemia mouse model and retrovirus expressing GFP labeling, we observed maturation of local generated new neurons. Furthermore, fate tracing studies using PDGFRα-, GFAP-, and Sox2-CreER mice showed a transient wave of neuroblast generation in mild ischemic cortex and further identified Sox2-positive astrocytes were the major neurogenic cells in adult cortex. In addition, a similar up-regulation of Sox2 and appearance of neuroblasts were observed in the focal ischemic cortex of Macaca Mulatta. Our data revealed a transient neurogenic response of Sox2-positive astrocytes in ischemic cortex, indicating the possibility of neuronal regeneration by amplifying this intrinsic response.

Key words: ischemia, cortex, local neurogenesis, astrocyte, Sox2, adult, fate-mapping, neural stem cells