Regulation of microglia polarization after cerebral ischemia

Abstract

Stroke ranks second as a leading cause of death and permanent disability globally. Microglia, innate immune cells in the brain, respond rapidly to ischemic injury, triggering a robust and persistent neuroinflammatory reaction throughout the disease’s progression. Neuroinflammation plays a critical role in the mechanism of secondary injury in ischemic stroke and is a significant controllable factor. Microglia activation takes on two general phenotypes: the pro-inflammatory M1 type and the anti-inflammatory M2 type, although the reality is more complex. The regulation of microglia phenotype is crucial to controlling the neuroinflammatory response. This review summarized the key molecules and mechanisms of microglia polarization, function, and phenotypic transformation following cerebral ischemia, with a focus on the influence of autophagy on microglia polarization. The goal is to provide a reference for the development of new targets for the treatment for ischemic stroke treatment based on the regulation of microglia polarization.

Role of microglia in stroke

“…Physiologic autophagy is also critical for microglia homeostasis (Beccari et al, 2023; Plaza‐Zabala et al, 2017). After stroke, autophagy seems to play complex roles in inflammation and phagocytosis (Peng et al, 2022; Plaza‐Zabala et al, 2017; Wang, Li, Zhang, et al, 2023). Alterations in the microglia autophagic flux after ischemia may impair their phagocytic activity since the autophagy‐inducing agent rapamycin improved phagocytosis of apoptotic neurons (Beccari et al, 2023).…”

Volume regulated anion channel blocker, DCPIB modulates microglial M1/M2 polarization via MAPK pathway and attenuates oxidative stress after AIS

“…Acute ischemic stroke (AIS) will quickly disrupt the homeostasis. Microglial M1/M2 polarization-mediated in ammation plays an essential role in the neuronal survival and neurological function recovery after AIS 4 . In the stroke event, resident microglia constitute the rst line of defense of the CNS against cerebral ischemia 5,6 .…”

“…In the stroke event, resident microglia constitute the rst line of defense of the CNS against cerebral ischemia 5,6 . Once AIS occurs, microglia are rapidly activated within several minutes and gradually become a double-edged sword with distinct phenotypic changes to the deleterious M1 phenotype, which secretes proin ammatory cytokines such as CD86, iNOS, TNF-α, IL-6 to trigger in ammation and bene cial M2 phenotype which secretes anti-in ammatory cytokines such as CD206, Arg-1, TGF-β, IL-10 to confer anti-in ammation and neuroprotection 4,7,8 . Excessive in ammation leads to a breakdown of the blood-brain barrier and in ltration of more immune cells, leading to progressive neuronal degeneration and loss of function.…”

Polyphyllin I alleviates neuroinflammation after cerebral ischemia–reperfusion injury via facilitating autophagy-mediated M2 microglial polarization

“…During cerebral ischemia, microglia can induce a robust and persistent inflammatory response throughout the progression of disease. Accumulated evidences demonstrate that microglia play an important role in cerebral ischemia injury and recovery (Wang et al 2023a ). Like peripheral macrophages, microglia are highly plastic and may rapidly polarize to either pro-inflammatory M1 phenotype or anti-inflammatory M2 phenotype in respond to environmental stimuli (Wang et al 2023a ).…”

“…Accumulated evidences demonstrate that microglia play an important role in cerebral ischemia injury and recovery (Wang et al 2023a ). Like peripheral macrophages, microglia are highly plastic and may rapidly polarize to either pro-inflammatory M1 phenotype or anti-inflammatory M2 phenotype in respond to environmental stimuli (Wang et al 2023a ). M1 microglia secrete pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6 to exacerbate inflammation and tissue damage, while M2 microglia produce anti-inflammatory cytokines like TGF-β, IL-4 and IL-13 to alleviate inflammation and promote tissue recovery (Xiong et al 2016 ).…”