Microglia in Post‐Traumatic Brain Injury (TBI) Cognitive Impairment: From Pathological Changes to Therapeutic Approaches

ABSTRACT Background 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. Method 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. Conclusions 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.