Microglia: A Double-Edged Sword in Intracerebral Hemorrhage From Basic Mechanisms to Clinical Research.

Jiachen Liu,Xiaoyu Wang,Gaiqing Wang,Qinqin Bai,Lirong Liu,Rundong Jiang

doi:10.3389/fimmu.2021.675660

Abstract

Microglia are the resident immune cells of the central nervous system (CNS). It is well established that microglia are activated and polarized to acquire different inflammatory phenotypes, either pro-inflammatory or anti-inflammatory phenotypes, which act as a critical component in the neuroinflammation following intracerebral hemorrhage (ICH). Microglia produce pro-inflammatory mediators at the early stages after ICH onset, anti-inflammatory microglia with neuroprotective effects appear to be suppressed. Previous research found that driving microglia towards an anti-inflammatory phenotype could restrict inflammation and engulf cellular debris. The principal objective of this review is to analyze the phenotypes and dynamic profiles of microglia as well as their shift in functional response following ICH. The results may further the understanding of the body’s self-regulatory functions involving microglia following ICH. On this basis, suggestions for future clinical development and research are provided.

Highlights

Microglia constitute 5% to 10% of adult brain cells and form the largest group of immune cells in the central nervous system (CNS) [1]
Peroxisome Proliferator-Activated Receptor Gamma (PPAR-g) The phagocytic activity of microglia is required to remove the hematoma after intracerebral hemorrhage (ICH); the pro-inflammatory mediators and free radicals released as a result of microglial activation and phagocytosis are toxic to neighboring cells and lead to secondary brain damage following ICH [80]
Minocycline, a widely available drug that alleviates brain damage, effectively reduces early upregulation of Matrix Metalloproteinases (MMPs)-12 expression [93, 94]and induces anti-inflammation microglial polarization, which reduces the levels of inflammatory cytokines and the number of microglia surrounding the hematoma after ICH [86]

Summary

INTRODUCTION

Microglia constitute 5% to 10% of adult brain cells and form the largest group of immune cells in the CNS [1]. Peroxisome Proliferator-Activated Receptor Gamma (PPAR-g) The phagocytic activity of microglia is required to remove the hematoma after ICH; the pro-inflammatory mediators and free radicals released as a result of microglial activation and phagocytosis are toxic to neighboring cells and lead to secondary brain damage following ICH [80]. Minocycline, a widely available drug that alleviates brain damage, effectively reduces early upregulation of MMP-12 expression [93, 94]and induces anti-inflammation microglial polarization, which reduces the levels of inflammatory cytokines and the number of microglia surrounding the hematoma after ICH [86]. Iron Chelators Iron overload is a significant cause of brain damage because iron toxicity contributes to pro-inflammatory microglial activation following collagenase-induced ICH. The target gene identified by multi-omics studies can potentially be used for drug repositioning in ICH, which is approved to be cheaper, quicker, and effective [102]

CONCLUSION

Result