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2022, Vol. 26 ›› Issue (14): 2265-2272Microglia in spinal cord injury: M1/M2 phenotypic polarization and neurotoxic/neuroprotective effectsLi Chuanhong, Yu Xing, Yang Yongdong, Zhao He
Abstract: BACKGROUND: A large number of studies have shown that microglia are activated after spinal cord injury, which play a dual role of neuroprotection and neurotoxicity, and are closely related to secondary spinal cord injury. OBJECTIVE: To review the characteristics of microglia’ M1/M2 phenotype after spinal cord injury, the progress in spinal cord injury intervention studies targeting M1/M2 phenotype and the possible research directions of microglia after spinal cord injury. METHODS: In May 2021, the first author searched PubMed database with the keywords of “microglia, spinal cord injury, M1 phenotype, M2 phenotype, polarization, activation, activated, regulation.” After reading the title and abstract, the retrieved articles were screened according to the inclusion and exclusion criteria. Finally, a total of 76 included literatures were summarized and reviewed. RESULTS AND CONCLUSION: Microglia have special biological functions due to its unique cell origin and development environment. In physiological state, microglia rely on its highly active branching process to continuously monitor the changes of microenvironment in the spinal cord tissue and play the function of immune surveillance. After spinal cord injury, microglia rapidly respond to abnormal microenvironmental signals and are polarized into M1 and M2 phenotypes, exerting neurotoxic and neuroprotective effects, respectively. A large number of basic experiments have demonstrated that interventions such as Chinese herbal extracts, clinical drugs, regulation of gene expression, cell transplantation, biomaterials can regulate the M1/M2 phenotype of microglia and improve the prognosis of spinal cord injury in a rodent model. However, no consensus has been reached on the optimal regulation target for the quantity and proportion of M1 and M2 phenotypes, and in vivo drug delivery targeting microglia is lacking. Future explorations should focus on promoting the functional balance between M1 and M2 phenotypes to limit the level of inflammatory response after spinal cord injury, which is conducive to repair of the injured spinal cord. With the further research on the precise regulation mechanism of microglial polarization phenotype after spinal cord injury, the results from basic research are correspondingly expected to be applied to clinical treatment. Key words:spinal cord injury, secondary spinal cord injury, microglia, M1 phenotype, M2 phenotype, inflammatory response, neuroprotection, review |