Li Ningcen, Lu Wenhui, Tang Limei, Zhu Lina, Deng Weibin, Liu Hang, Huang Changquan, Jin Jingying, Zeng Jingjiao, Chen Shitai, Geng Lianqi, Hu Xiuwu, Zhou Liang
Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Affiliated Rehailitation Hospital of Nanchang University, Jiangxi, China.
CNS Neurosci Ther. 2025 Aug;31(8):e70568. doi: 10.1111/cns.70568.
Traumatic brain injury (TBI), as a common and serious neurological disease, brings enormous physical and psychological burden to patients. Among them, cognitive impairment caused by TBI greatly affects the quality of life and social function of patients. Microglia, as key immune cells in the central nervous system, play a crucial role in the occurrence and development of cognitive impairment after TBI. This review delves into the important functions of microglia in normal physiological states and their multifaceted manifestations in post-TBI cognitive impairment.
A systematic literature review was conducted using PubMed, Google Scholar, Web of Science and Scopus, with a focus on preclinical studies as well as clinical trials published in the past 20 years. The key search terms include "traumatic brain injury," "cognitive impairment," "microglia," etc. RESULTS: During the acute phase of TBI injury, microglia rapidly activate, clear injury debris, and initiate repair, reducing secondary injury. At the same time, microglia undergo phenotype polarization during this stage. Some M1-type microglia can release various inflammatory factors through inflammation-related pathways, triggering inflammatory signals and leading to neuronal apoptosis and neuroinflammatory responses. M1 polarization driven persistent inflammation becomes an important factor in the chronic progression of TBI, leading to cognitive impairment. On the other hand, the phagocytic function of activated microglia also changes, which may lead to excessive phagocytosis of normal neurons and synapses, causing synaptic dysfunction and further exacerbating cognitive impairment. Meanwhile, insufficient clearance of damaged cells and debris can lead to persistent inflammation, hindering nerve repair. This review also provides a detailed introduction to potential treatment methods. This includes inhibiting the activation of microglia and the release of inflammatory factors through anti-inflammatory therapy, regulating the phenotype of microglia to promote their transformation to M2 type, promoting the normalization of microglial phagocytic function, regulating the structure and function of synapses, and using stem cell therapy to secrete neurotrophic factors to regulate microglial function. The strategy of integrating traditional Chinese and Western medicine is also a good direction.
Microglia are both the "driving force" of neuroinflammation and the "key executor" of repair in post-TBI cognitive impairment. Their dual effect is dynamically influenced by multiple factors. Future treatments require precise targeting of polarization balance, combined with spatiotemporal specific intervention strategies, to break the vicious cycle of chronic inflammation and promote neurological function recovery.
创伤性脑损伤（TBI）作为一种常见且严重的神经系统疾病，给患者带来了巨大的身心负担。其中，TBI所致的认知障碍极大地影响了患者的生活质量和社会功能。小胶质细胞作为中枢神经系统中的关键免疫细胞，在TBI后认知障碍的发生和发展中起着至关重要的作用。本综述深入探讨了小胶质细胞在正常生理状态下的重要功能及其在TBI后认知障碍中的多方面表现。
使用PubMed、谷歌学术、科学网和Scopus进行系统的文献综述，重点关注过去20年发表的临床前研究以及临床试验。关键检索词包括“创伤性脑损伤”、“认知障碍”、“小胶质细胞”等。结果：在TBI损伤的急性期，小胶质细胞迅速激活，清除损伤碎片并启动修复，减少继发性损伤。同时，小胶质细胞在此阶段会发生表型极化。一些M1型小胶质细胞可通过炎症相关途径释放各种炎症因子，触发炎症信号并导致神经元凋亡和神经炎症反应。由M1极化驱动的持续性炎症成为TBI慢性进展的重要因素，导致认知障碍。另一方面，活化小胶质细胞的吞噬功能也发生改变，这可能导致对正常神经元和突触的过度吞噬，引起突触功能障碍并进一步加剧认知障碍。同时，受损细胞和碎片的清除不足会导致持续性炎症，阻碍神经修复。本综述还详细介绍了潜在的治疗方法。这包括通过抗炎治疗抑制小胶质细胞的激活和炎症因子的释放，调节小胶质细胞的表型以促进其向M2型转化，促进小胶质细胞吞噬功能的正常化，调节突触的结构和功能，以及使用干细胞疗法分泌神经营养因子来调节小胶质细胞功能。中西医结合策略也是一个很好的方向。
小胶质细胞既是神经炎症的“驱动力”，也是TBI后认知障碍修复的“关键执行者”。它们的双重作用受到多种因素的动态影响。未来的治疗需要精确靶向极化平衡，结合时空特异性干预策略，打破慢性炎症的恶性循环，促进神经功能恢复。
