Abstract
Ischemic stroke, which is the second highest cause of death and the leading cause of disability, represents ~71% of all strokes globally. Some studies have found that the key elements of the pathobiology of stroke is immunity and inflammation. Microglia are the first line of defense in the nervous system. After stroke, the activated microglia become a double-edged sword, with distinct phenotypic changes to the deleterious M1 types and neuroprotective M2 types. Therefore, ways to promote microglial polarization toward M2 phenotype after stroke have become the focus of attention in recent years. In this review, we discuss the process of microglial polarization, summarize the alternation of signaling pathways and epigenetic regulation that control microglial polarization in ischemic stroke, aiming to find the potential mechanisms by which microglia can be transformed into the M2 polarized phenotype.
Highlights
Stroke is the second leading cause of death and the highest disabling disease in the world, with an increasing incidence in developing countries [1,2,3]
Interferon γ (IFN γ) secreted by T helper 1 cells activates signal transducer and activator of transcription 1 (STAT1) factor through Janus kinase (JAK)1/JAK2 signaling, inducing M1 microglia to produce pro-inflammatory cytokines [24]. Another pathway is activited by lipopolysaccharide (LPS) or damage-associated molecular pattern (DAMP) stimulation accompanied with Toll-like receptor 4 (TLR4) [25, 26]
The protection of HDAC inhibitors (HDACi) on microglia polarization is involved in its anti-inflammatory effect in the early phase of cerebral ischemia, reducing the activation of microglia and promote activated microglia to protective phenotype, providing a promising therapeutic intervention [102, 103]
Summary
Stroke is the second leading cause of death and the highest disabling disease in the world, with an increasing incidence in developing countries [1,2,3]. Being the key innate immune cells, microglia act as guardians responding to various acute brain injuries, including ischemic stroke[8, 9]. The function of microglial cells changed with aging and the morphology of the microglia is more de-ramified [14]. The existence of an aging-related microglial phenotype in the aged human brain is verified and it is involved in pathological processes of CNS diseases [16]. Microglia could present different phenotypes in accordance with the stimulus, the environment, and the period, which is called microglial polarization [17, 18]. Microglia play an important role in various neurological diseases, involving in multiple aspects of neuroinflammation, such as cytotoxicity, repair, immunosuppression and regeneration at the basis of different polarization states [21].
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