Modulators of microglia activation and polarization in ischemic stroke (Review)

Abstract

ischemic stroke is one of the leading causes of mortality and disability worldwide. However, there is a current lack of effective therapies available. as the resident macrophages of the brain, microglia can monitor the microenvironment and initiate immune responses. in response to various brain injuries, such as ischemic stroke, microglia are activated and polarized into the proinflammatory M1 phenotype or the anti-inflammatory M2 phenotype. The immunomodulatory molecules, such as cytokines and chemokines, generated by these microglia are closely associated with secondary brain damage or repair, respectively, following ischemic stroke. it has been shown that M1 microglia promote secondary brain damage, whilst M2 microglia facilitate recovery following stroke. in addition, autophagy is also reportedly involved in the pathology of ischemic stroke through regulating the activation and function of microglia. Therefore, this review aimed to provide a comprehensive overview of microglia activation, their functions and changes, and the modulators of these processes, including transcription factors, membrane receptors, ion channel proteins and genes, in ischemic stroke. The effects of autophagy on microglia polarization in ischemic stroke were also reviewed. Finally, future research areas of ischemic stroke and the implications of the current knowledge for the development of novel therapeutics for ischemic stroke were identified. Contents 1. introduction 2. Microglia 3. Modulatory mechanisms of microglia polarization 4. autophagy 5. conclusions

P2X7R-mediated Autophagic Impairment Contributes to Central Sensitization in a chronic Migraine Model with Recurrent Nitroglycerin Stimulation in Mice

“…Previous studies have shown that autophagy regulates the activation of microglia and in ammatory response [69][70][71]. The activation of NLRP3 in ammasome is inhibited by autophagy through the clearance of damaged mitochondria degradation of the NLRP3 in ammasome [42,72,73].…”

Microglia Fighting for Neurological and Mental Health: On the Central Nervous System Frontline of COVID-19 Pandemic

“…Hypoxia also triggers rodent microglial transcription factors (e.g., hypoxia inducible factor 1, alpha subunit and NFKB), and micro RNAs (miR-s) (e.g., miR-146a, and miR181a/c), both in vitro and in vivo ; resulting in the release of TNFA, ROS, IL1B, and IL18, which can help clear cellular debris and resolve the injury ( Zhang et al, 2012 ; Kong et al, 2014 ; Kiernan et al, 2016 ; Mukandala et al, 2016 ; Jiang et al, 2020 ; Yang et al, 2020b ). In response to ischemia-hypoxia, rodent microglia likewise transform morphologically (see Figure 1 ; Masuda et al, 2011 ).…”

Impact of hydroxytyrosol on stroke: tracking therapy response on neuroinflammation and cerebrovascular parameters using PET-MR imaging and on functional outcomes

“…The balance between pro- and anti-inflammatory stimuli drives the functional polarization of many immune cells such as microglia/macrophages (Iba-1 + , F4/80 + , CD11b + cells), astrocytes (GFAP + cells) and neutrophils into beneficial or detrimental phenotypes 8 , 9 . In stroke, microglia/macrophages showed an enhanced beneficial anti-inflammatory phenotype within the first week, but expressed a more detrimental pro-inflammatory genes signature at later stages 8 , 10 , peaking around day 14 post ischemia 11 . However, the concept of differential waves of anti- and pro-inflammatory microglia is still too simplistic to illustrate the complex spatiotemporal changes of the transcriptomic and proteomic microglial profile in response to injury 12 , 13 .…”