Microglia-mediated neuroinflammation and neuroplasticity after stroke

Abstract

Stroke remains a major cause of long-term disability and mortality worldwide. The immune system plays an important role in determining the condition of the brain following stroke. As the resident innate immune cells of the central nervous system, microglia are the primary responders in a defense network covering the entire brain parenchyma, and exert various functions depending on dynamic communications with neurons, astrocytes, and other neighboring cells under both physiological or pathological conditions. Microglia activation and polarization is crucial for brain damage and repair following ischemic stroke, and is considered a double-edged sword for neurological recovery. Microglia can exist in pro-inflammatory states and promote secondary brain damage, but they can also secrete anti-inflammatory cytokines and neurotrophic factors and facilitate recovery following stroke. In this review, we focus on the role and mechanisms of microglia-mediated neuroinflammation and neuroplasticity after ischemia and relevant potential microglia-based interventions for stroke therapy.

Regulatory T cells promote functional recovery after spinal cord injury by alleviating microglia inflammation via STAT3 inhibition

“…Microglia play a central role in neuroinflammation through the release of multiple cytokines and chemokines 50 . Importantly, our findings indicated that Tregs may improve the injured spinal microenvironment through regulating microglia activation.…”

The Implications of Microglial Regulation in Neuroplasticity-Dependent Stroke Recovery

“…M1 activation, known as the classically activated phenotype, is induced by lipopolysaccharide (LPS), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interferon-γ (IFN-γ), and is thought to be a pro-inflammatory and neurotoxic state. It is characterized by the secretion of pro-inflammatory cytokines and chemokines such as interleukin (IL)-1β, IL-6, IL-12, and tumor necrosis factor-α (TNF-α) as well as the production of neurotoxic substances, including ROS, inducible nitric oxide synthase (iNOS), and proteolytic enzymes including matrix metalloproteinase (MMP)3 and MMP9 [ 9 , 86 , 87 , 88 ]. Double-negative T cells (DNTs) have been found to secrete large amounts of TNF-α, promoting the activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and inducing microglia pro-inflammatory polarization [ 89 ].…”

“…M2 activation, also known as alternatively activated, is induced by IL-4, IL-13, and IL-10 to secrete anti-inflammatory cytokines, such as IL-10 and transforming growth factor-β (TGF-β). They also release growth factors such as insulin-like growth factor-1 (IGF-1), colony-stimulating factor-1 (CSF-1), vascular endothelial growth factor (VEGF), and neurotrophins such as brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF), and their markers such as arginase-1 (Arg-1), chitinase-like protein 3 (also known as Ym1), cluster of differentiation (CD)163, and CD206, which are involved in tissue regeneration and repair, removal of cell debris, provision of trophic factors, and preservation of tissue dynamics following infection or damage [ 9 , 75 , 86 , 87 , 91 , 92 ]. The M2 phenotype can be further divided into three subclasses: M2a, M2b, and M2c [ 93 ].…”

“…In summary, microglia exhibit distinct activation profiles depending on the different brain microenvironments and undergo temporal and spatial adaptations to switch their phenotypes depending on the site and severity of the brain injury [ 7 ]. As immune cells in the CNS, microglial activation is involved in various aspects of neuroplasticity, such as neuronal connection, axonogenesis, dendritic spine reorganization, and endogenous neurogenesis [ 9 , 117 ]. It plays a key role in regulating local and global brain inflammation and in promoting neurological recovery.…”

“…They participate in a variety of pathophysiological processes in the brain, including the promotion of neuronal survival, induction of programmed cell death, immune monitoring and antigen presentation, inflammation regulation, modulation of synaptic activity, synaptic pruning, remodeling, etc. [ 8 , 9 , 10 , 11 , 12 ].…”