Neural Regeneration Research ›› 2024, Vol. 19 ›› Issue (12): 2588-2601.doi: 10.4103/NRR.NRR-D-23-01775

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A core scientific problem in the treatment of central nervous system diseases: newborn neurons

Peng Hao1, Zhaoyang Yang1, *, Kwok-Fai So2, 3, 4, 5, 6, *, Xiaoguang Li1, 7, *   

  1. 1Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China; 2Guangdong-HongKong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, Guangdong Province, China; 3Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, Guangdong Province, China; 4Department of Ophthalmology and State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong Special Administration Region, China; 5Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong-Macao Greater Bay Area, Guangzhou, Guangdong Province, China; 6Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China; 7Department of Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
  • Online:2024-12-15 Published:2024-03-30
  • Contact: Kwok-Fai So, PhD, hrmaskf@hku.hk; Zhaoyang Yang, PhD, wack lily@163.com; Xiaoguang Li, PhD, lxgchina@sina.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 82272171(to ZY), 82271403 (to XL), 31971279 (to ZY), 81941011 (to XL), 31730030 (to XL).

Abstract: It has long been asserted that failure to recover from central nervous system diseases is due to the system’s intricate structure and the regenerative incapacity of adult neurons. Yet over recent decades, numerous studies have established that endogenous neurogenesis occurs in the adult central nervous system, including humans’. This has challenged the long-held scientific consensus that the number of adult neurons remains constant, and that new central nervous system neurons cannot be created or renewed. Herein, we present a comprehensive overview of the alterations and regulatory mechanisms of endogenous neurogenesis following central nervous system injury, and describe novel treatment strategies that target endogenous neurogenesis and newborn neurons in the treatment of central nervous system injury. Central nervous system injury frequently results in alterations of endogenous neurogenesis, encompassing the activation, proliferation, ectopic migration, differentiation, and functional integration of endogenous neural stem cells. Because of the unfavorable local microenvironment, most activated neural stem cells differentiate into glial cells rather than neurons. Consequently, the injury-induced endogenous neurogenesis response is inadequate for repairing impaired neural function. Scientists have attempted to enhance endogenous neurogenesis using various strategies, including using neurotrophic factors, bioactive materials, and cell reprogramming techniques. Used alone or in combination, these therapeutic strategies can promote targeted migration of neural stem cells to an injured area, ensure their survival and differentiation into mature functional neurons, and facilitate their integration into the neural circuit. Thus can integration replenish lost neurons after central nervous system injury, by improving the local microenvironment. By regulating each phase of endogenous neurogenesis, endogenous neural stem cells can be harnessed to promote effective regeneration of newborn neurons. This offers a novel approach for treating central nervous system injury.

Key words: bioactive materials, brain trauma, endogenous neurogenesis, hippocampal dentate gyrus, neural stem cells, neurotrophic factors, newborn neurons, spinal cord injury, stroke, subventricular zone