Zhao Jing-Yu, Zhou Yang, Zhou Chao-Wen, Zhan Ke-Bin, Yang Ming, Wen Ming, Zhu Ling-Qiang
Department of Neurosurgery, Wuhan Hankou Hospital, Hankou Hospital Affiliated to Wuhan University of Science and Technology, Jiang`an District, Wuhan, People's Republic of China.
Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Int J Surg. 2025 Jun 1;111(6):3942-3978. doi: 10.1097/JS9.0000000000002420. Epub 2025 May 12.
Traumatic brain injury (TBI) triggers a complex neuroinflammatory cascade, with microglia serving as key regulators of both pathological damage and tissue structural restoration. Despite extensive research, the precise temporal evolution of microglial activation and its implications for long-term neurological outcomes remain incompletely understood. Here, we provide a comprehensive review of the molecular and cellular mechanisms underlying microglial responses in TBI, highlighting their role in neuroinflammation, neurogenesis, and tissue remodeling. We systematically compare clinical and preclinical TBI classifications, lesion patterns, and animal modeling strategies, evaluating their translational relevance. Furthermore, we explore the limitations of the conventional M1/M2 dichotomy and emphasize recent insights from single-cell transcriptomic analyses that reveal distinct microglial subpopulations across different injury phases. Finally, we discuss current therapeutic strategies targeting microglial modulation and propose future directions for neuroimmune interventions in TBI. By integrating findings from experimental and clinical studies, this review aims to bridge mechanistic insights with therapeutic advancements, paving the way for precision-targeted neuroimmune therapies.
创伤性脑损伤(TBI)引发复杂的神经炎症级联反应,其中小胶质细胞是病理损伤和组织结构修复的关键调节因子。尽管进行了广泛研究,但小胶质细胞激活的确切时间演变及其对长期神经学结果的影响仍未完全明确。在此,我们全面综述了TBI中小胶质细胞反应的分子和细胞机制,强调它们在神经炎症、神经发生和组织重塑中的作用。我们系统比较了临床和临床前TBI的分类、损伤模式及动物建模策略,评估它们的转化相关性。此外,我们探讨了传统M1/M2二分法的局限性,并强调单细胞转录组分析的最新见解,这些见解揭示了不同损伤阶段不同的小胶质细胞亚群。最后,我们讨论了目前针对小胶质细胞调节的治疗策略,并提出TBI神经免疫干预的未来方向。通过整合实验和临床研究的结果,本综述旨在将机制见解与治疗进展联系起来,为精准靶向神经免疫治疗铺平道路。