Microglia-associated neuroinflammation is a potential therapeutic target for ischemic stroke

Abstract

Microglia-associated neuroinflammation plays an important role in the pathophysiology of ischemic stroke. Microglial activation and polarization, and the inflammatory response mediated by these cells play important roles in the development, progression and outcome of brain injury after ischemic stroke. Currently, there is no effective strategy for treating ischemic stroke in clinical practice. Therefore, it is clinically important to study the role and regulation of microglia in stroke. In this review, we discuss the involvement of microglia in the neuroinflammatory process in ischemic stroke, with the aim of providing a better understanding of the relationship between ischemic stroke and microglia.

Keywords: brain; cells; central nervous system; inflammation; injury; macrophages; repair; review; stroke.

Figure 1

Phenotypic polarization of microglia. Microglia become polarized towards the M1 or M2 phenotype at various stages after central nervous system injuries, and have distinct roles in the restoration of the neurovascular network. M1 phenotypic microglia mainly secrete proinflammatory factors such as IL-1, IL-6, TNF-α and IFN-γ, which have cytotoxic effects on neurons, resulting in neuronal loss. The M2 phenotype mainly secretes anti-inflammatory factors such as IL-3, IL-4, IL-10, TGF-β and IGF-1 to inhibit inflammation. M2 microglia also produce the anti-oxidative factors HO-1 and GSH, which may reduce neuronal loss and promote neuronal repair. GSH: Glutathione; HO-1: heme oxygenase-1; IFN-γ: interferon-γ; IGF-1: insulin-like growth factor-1; IL: interleukin; TGF-β: transforming growth factor-β; TNF-α: tumor necrosis factor-α.

Figure 2

Activated microglial cells secrete inflammatory cytokines. CCL2/CCR2, sFasL and LPS can activate M1 microglial cells, and activated M1 microglial cells can secrete inflammatory cytokines, such as IL-1β, IL-6 and TNF-α. PPARγ, SOCS1/JAK2/STAT3, AMPK and IRF-4 can activate M2 microglial cells, and activated M2 microglial cells can secrete inflammatory cytokines, such as IL-4, IL-10 and TGF-β. AMPK: Adenosine 5'-monophosphate-activated protein kinase; CCL2: chemokine ligand-2; CCR2: chemokine ligand receptor-2; IL: interleukin; IRF-4: interferon regulatory factor-4; LPS: lipopolysaccharide; PPARγ: peroxisome proliferator-activated receptor γ; sFasL: soluble Fas ligand; SOCS1/JAK2/STAT3: suppressor of cytokine signaling 1/Janus kinase 2/signal transducer and activator of transcription 3; TGF-β: transforming growth factor-β; TNFR1: tumor necrosis factor receptor 1; TNF-α: tumor necrosis factor-α; TREM-1: triggering receptor expressed on myeloid cells-1.