The mechanism of microglia-mediated immune inflammation in ischemic stroke and the role of natural botanical components in regulating microglia: A review

Abstract

Ischemic stroke (IS) is one of the most fatal diseases. Neuroimmunity, inflammation, and oxidative stress play important roles in various complex mechanisms of IS. In particular, the early proinflammatory response resulting from the overactivation of resident microglia and the infiltration of circulating monocytes and macrophages in the brain after cerebral ischemia leads to secondary brain injury. Microglia are innate immune cells in the brain that constantly monitor the brain microenvironment under normal conditions. Once ischemia occurs, microglia are activated to produce dual effects of neurotoxicity and neuroprotection, and the balance of the two effects determines the fate of damaged neurons. The activation of microglia is defined as the classical activation (M1 type) or alternative activation (M2 type). M1 type microglia secrete pro-inflammatory cytokines and neurotoxic mediators to exacerbate neuronal damage, while M2 type microglia promote a repairing anti-inflammatory response. Fine regulation of M1/M2 microglial activation to minimize damage and maximize protection has important therapeutic value. This review focuses on the interaction between M1/M2 microglia and other immune cells involved in the regulation of IS phenotypic characteristics, and the mechanism of natural plant components regulating microglia after IS, providing novel candidate drugs for regulating microglial balance and IS drug development.

Perspective from single‐cell sequencing: Is inflammation in acute ischemic stroke beneficial or detrimental?

“…2 Ultimately, understanding the detailed mechanisms of microglial activation and polarization will contribute to shifting microglial cells from harmful to protective phenotypes. 8,41 High-mobility group box 1 (HMGB1) is a potent pro-inflammatory mediator that promotes M1 polarization in microglial cells. In one study, Gao et al found that the inhibition of HMGB1 could induce M2 polarization of microglial cells, thereby alleviating traumatic brain injury.…”

“…Specifically, LP1 and CD72 have been implicated in the clearance and recycling of lipid debris and regulation of microglial cell proliferation, 40 and their specific upregulation in microglial cells after MCAO may be associated with tissue repair 2 . Ultimately, understanding the detailed mechanisms of microglial activation and polarization will contribute to shifting microglial cells from harmful to protective phenotypes 8,41 …”

“…Neuroinflammation and oxidative stress play significant roles in the diverse complex mechanisms of AIS 8 . The activation of resident cells, including microglia, astrocytes, oligodendrocytes, and endothelial cells, following AIS can promote brain regeneration and recovery.…”

“…6,7 Neuroinflammation and oxidative stress play significant roles in the diverse complex mechanisms of AIS. 8 The activation of resident cells, including microglia, astrocytes, oligodendrocytes, and endothelial cells, following AIS can promote brain regeneration and recovery. However, these cells can also recruit immune cells expressing inflammatory mediators, causing disruption of the blood-brain barrier (BBB), neuronal death, brain edema, and hemorrhagic transformations.…”

Grafting of electrically stimulated subventricular neural stem cells embedded in a nutritional hydrogel into the stroke cavity improved cell survival and behavioural recovery in mice

“…Neuroin ammation after ischemic stroke can exacerbate tissue injury and delay the healing and recovery process. Thus, after stroke microglial cells can acquire an M1 phenotype and release pro-in ammatory factors including IL-1β, -6, and TNF-α leading to the suppression of neurogenesis, neuronal apoptosis thereby increasing neurological de cits, especially in aged subjects [13,14].…”