Individual in vivo Profiles of Microglia Polarization After Stroke, Represented by the Genes iNOS and Ym1

Abstract

Microglia are the brain-innate immune cells which actively surveil their environment and mediate multiple aspects of neuroinflammation, due to their ability to acquire diverse activation states and phenotypes. Simplified, M1-like microglia are defined as pro-inflammatory cells, while the alternative M2-like cells promote neuroprotection. The modulation of microglia polarization is an appealing neurotherapeutic strategy for stroke and other brain lesions, as well as neurodegenerative diseases. However, the activation profile and change of phenotype during experimental stroke is not well understood. With a combined magnetic resonance imaging (MRI) and optical imaging approach and genetic targeting of two key genes of the M1- and M2-like phenotypes, iNOS and Ym1, we were able to monitor in vivo the dynamic adaption of the microglia phenotype in response to experimental stroke.

GW0742 activates miR‐17‐5p and inhibits TXNIP/NLRP3‐mediated inflammation after hypoxic‐ischaemic injury in rats and in PC12 cells

“…Quantitative analysis of microglia activation revealed a significant reduction in Iba‐1 + cell numbers (Figure 4C, P < 0.01), as well as decreased soma size (Figure 4D, P < 0.01) in GW0742‐treated rats in ipsilateral hemisphere compared to vehicle group. To further validate our findings, we stained brain sections with a marker of activated microglia CD68 together with iNOS, which is expressed by pro‐inflammatory microglia 31 . Colocalization of CD68 and iNOS is indicative of a pro‐inflammatory microglia phenotype.…”

“…To further validate our findings, we stained brain sections with a marker of activated microglia CD68 together with iNOS, which is expressed by pro-inflammatory microglia. 31 Colocalization of CD68 and iNOS is indicative of a pro-inflammatory microglia phenotype.…”

Modulators of microglia activation and polarization in ischemic stroke (Review)

“…Following ischemic stroke, M1 microglia are activated and subsequently serve a detrimental role. Briefly, upon experiencing ischemia/hypoxia, NF-κB is activated within microglia and translocates from the cytoplasm to the nucleus; this activates the release of proinflammatory cytokines, which causes secondary brain damage (16)(17)(18), such as interleukin (il)-1β (24), il-6 (25) and tumor necrosis factor-α (TnF-α) (26), in addition to the production of inducible nitric oxide synthase (iNOS) (27,28). For example, in middle cerebral artery occlusion (Mcao) model mice, TnF-α secreted by M1 microglia was identified to increase endothelial necroptosis and BBB leakage following ischemic stroke (21,29).…”

“…The activation of M2 microglia can be assessed by determining the expression levels of their surface markers (Table I), for example, macrophage mannose receptor 1 (CD206) (59), and the secretion of anti-inflammatory cytokines, including il-4 (23), il-10 (59), arginase-1 (arg-1) (60), Ym1 (28) and TGF-β (59). changes in the percentage of activated M2 microglia can affect stroke prognosis and based on these changes, it is possible to draw some useful conclusions regarding ischemic stroke; for example, in MCAO model mice (44), the mRNA expression levels of cytokines generated by M2 microglia, including Arg-1, Ym1/2, CCL22, IL-10 and TGF-β, were detected from days 1 to 3 following Mcao and peaked at days 3 to 5 post-injury in ischemic regions (44).…”

Pyruvate enhances M1 microglial polarization via NF-κB/MCT1/iNOS signaling axis under low glucose condition

“…They survey the microenvironment and respond quickly to events from microbial invasion [1], trauma [2], chronic neurodegenerative diseases [3][4][5][6] to a variety of signaling [7]. A multitude of functions have been assigned to microglia [8], including secretion of pro-in ammatory cytokines, phagocytosis of cellular debris [9,10], support of neuronal growth [11][12][13] and re-myelination [14][15][16]. M1 microglia initiate the in ammatory response in early stages of injury [17,18] and express marker proteins like inducible nitric oxide synthase (iNOS), CD16/32 and CD14; whereas, the M2 microglia express arginase-1 (ARG1), CD206 and Y1 and carry out tissue repair during the later stage of injury [19][20][21].…”