Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (3): 821-835.doi: 10.4103/NRR.NRR-D-23-01446

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Repetitive traumatic brain injury–induced complement C1–related inflammation impairs long-term hippocampal neurogenesis

Jing Wang1, 2, Bing Zhang3, 4, Lanfang Li3, 4, Xiaomei Tang3, 4, Jinyu Zeng3, 4, Yige Song3, 4, Chao Xu5, Kai Zhao1, Guoqiang Liu6, Youming Lu3, 4, Xinyan Li3, 4, 7, *, Kai Shu1, *   

  1. 1Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China; 2Department of Neurosurgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China; 3Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China; 4Institute for Brain Research, Wuhan Center of Brain Science, Huazhong University of Science and Technology, Wuhan, Hubei Province, China; 5Department of Graduate Student, Chongqing Medical University, Chongqing, China; 6Department of Basic Medicine, School of Medical Science, Hubei University for Nationalities, Enshi, Hubei Province, China; 7Department of Anatomy, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
  • Online:2025-03-15 Published:2024-06-26
  • Contact: Kai Shu, MD, PhD, kshu@tjh.tjmu.edu.cn; Xinyan Li, MD, PhD, lixinyan1026@163.com.
  • Supported by:
    This work was supported by the Fundamental Research Program of Shanxi Province of China, No. 20210302124277 and the Science Foundation of Shanxi Bethune Hospital, No. 2021YJ13 (both to JW).

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Abstract: Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus, leading to long-term cognitive impairment. However, the mechanism underlying this neurogenesis impairment remains unknown. In this study, we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury. Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development, delayed neuronal maturation, and reduced the complexity of neuronal dendrites and spines. Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval. Moreover, following repetitive traumatic brain injury, neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased, C1q binding protein levels were decreased, and canonical Wnt/β-catenin signaling was downregulated. An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function. These findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.

Key words: complement C1, dendrite, dentate gyrus, hippocampus, neural stem cell, neurogenesis, neuroinflammation, neurological function, neuron, traumatic brain injury