Neuroinflammation of microglia polarization in intracerebral hemorrhage and its potential targets for intervention

Abstract

Microglia are the resident immune cells of the central nervous system (CNS) and play a key role in neurological diseases, including intracerebral hemorrhage (ICH). Microglia are activated to acquire either pro-inflammatory or anti-inflammatory phenotypes. After the onset of ICH, pro-inflammatory mediators produced by microglia at the early stages serve as a crucial character in neuroinflammation. Conversely, switching the microglial shift to an anti-inflammatory phenotype could alleviate inflammatory response and incite recovery. This review will elucidate the dynamic profiles of microglia phenotypes and their available shift following ICH. This study can facilitate an understanding of the self-regulatory functions of the immune system involving the shift of microglia phenotypes in ICH. Moreover, suggestions for future preclinical and clinical research and potential intervention strategies are discussed.

Egr1 promotes Nlrc4-dependent neuronal pyroptosis through phlda1 in an in-vitro model of intracerebral hemorrhage

“…In addition, microglia react to sudden brain damage by being activated and polarized to M1-like (pro-inflammatory) or M2-like (anti-inflammatory) phenotype [35]. Early-stage microglia M1-like mediators can cause neuroinflammation, but switching to M2-like microglia can reduce inflammation and promote recovery [36]. Encouraging M2 polarization and suppressing M1 polarization can alleviate the brain injury caused by ICH [37].…”

Pink1 deficiency enhances neurological deficits and inflammatory responses after intracerebral hemorrhage in mice

“…As resident immune cells in the central nervous system, microglia not only remove the hematoma and clear debris but also make M1 and M2 phenotype change to produce pro-inflammatory cytokines and neuroprotective anti-inflammatory cytokines to determine the progression of ICH [ 13 , [17] , [18] , [19] ]. In LPS/IFN-γ stimulated inflammation, Pink1 deficiency can attenuate expression of both pro-inflammatory and anti-inflammatory cytokines in microglia, while enhancing pro-inflammatory phenotypes of mixed astrocytes/microglia and pure astrocytes [ 20 ].…”

Stroke Related Brain–Heart Crosstalk: Pathophysiology, Clinical Implications, and Underlying Mechanisms

“…[ 144 , 145 , 146 ] Microglia/macrophages undergo polarization to the M1‐phenotype, traversing the damaged BBB and being attracted into the brain tissue injured site. [ 146 , 147 ] Subsequently, an intensified local inflammatory response is triggered, characterized by elevated levels of cytokines, chemokines, astrogliosis, microgliosis, and endothelial cell activation. [ 146 ] Concurrently, elevated levels of matrix metalloproteinases (MMP) and oxidative stress contribute to endothelial cell damage post‐stroke, further aggravating BBB injury and subsequent formation of vasogenic edema.…”

“…[ 146 , 147 ] Subsequently, an intensified local inflammatory response is triggered, characterized by elevated levels of cytokines, chemokines, astrogliosis, microgliosis, and endothelial cell activation. [ 146 ] Concurrently, elevated levels of matrix metalloproteinases (MMP) and oxidative stress contribute to endothelial cell damage post‐stroke, further aggravating BBB injury and subsequent formation of vasogenic edema. [ 148 , 149 ] Consequently, peripheral immune cells are recruited into the cerebral microcirculation and ischemic brain tissue, subsequently crossing the damaged BBB through activation of the sympathetic nervous system and the HPA axis.…”