Microglia, considered the long-living resident immune cells of the brain, play a vital role in BBB function. M2 microglia promote oligodendrocyte precursor cells survival and differentiation, and further enhance white matter repair. Microglia as Regulators of Neuronal Function and Plasticity Microglia are resident immune cells in the brain and spinal cord. M2 macrophages produce high levels of IL-10, TGF-beta and low levels of IL-12. Alternatively activated M2 microglia are divided into three subtypes—M2a, M2b, and M2c—each with different cell surface markers and distinct biological functions: M2a microglia mainly contribute to cell regeneration, whereas M2b and M2c cells participate in … IL-4 is mostly used to induce the M2 phenotype . Upon M2 polarization, microglia and macrophages were found to express similar genes with the exception of CD64 that was observed in both M1 and M2 microglia. M2 is the phenotype of resident tissue macrophages, and can be further elevated by IL-4. In this study, we hypothesized that M2 BV2-derived exosomes (M2-EXO) exert neuroprotective effects in the ischemic mouse brain via transfer of miR-124 into neurons and regulation of its corresponding downstream genes. 2. Microglia are able to polarize along two pathways, classic M1 and alternative M2, towards tissue injury and tissue repair respectively. Rosiglitazone-induced PPAR-γ activation promoted microglia polarization to the M2 phenotype, which reduced the inflammatory response, attenuated axonal injury in the cerebral cortex, and improved neurological function. ELISA analysis for the M1-microglia-associated markers iNOS and TNFα (A,B) and the M2-microglia-associated markers TREM-2 … Additionally, the M1 or M2 microglia phenotypes could have a detrimental or beneficial outcome depending on the disease context, and more detailed analysis is required. M2 microglia represent alternative activation with expression of arginase 1, CD206, Ym1, Fizz1. S7). Here, we explored the effect and mechanism of M2 microglia-derived exosomes on white matter repair … M1- and M2-microglia associated markers and MyD88, NF-κB p65, and NLRP3 signaling were altered after TAK-242 treatment in APP/PS1 transgenic mice. Microglia, the resident immune cells of the central nervous system, respond to the acute brain injury through activation and polarization. M2 macrophages are alternatively activated by exposure to certain cytokines such as IL-4, IL-10, or IL-13. However, M2-polarized macrophages induced by IL-4 cannot attenuate the functional outcome and lesion size caused by cerebral ischemia. These pro-inflammatory and anti-inflammatory states have been also described as M1 and M2 respectively. n addition, autophagy is also reportedly involved in i the pathology of ischemic stroke through regulating the activa - tion and function of microglia. The cells were subsequently harvested, fixed, then analyzed by flow cytometry using the OX-42 antibody. A combination of both M1 and M2 stimuli is then used to differentiate microglia into an intermediate M1/M2 polarization phenotype (state 3). literature. Microglia can also directly interact with endothelial cells and affect BBB permeability. activated (M2) human microglia in the inflamed brain. Microglia cells display two main activation phenotypes owing to the intracellular signals within their surroundings (31–33). Microglia are the principal resident immune cells in the central nervous system and are believed to be versatile players in both inflammatory and physiological contexts. Finally, to study the polarity switch between M1 and M2 states, microglia are stimulated firstly with anti-inflammatory stimuli, washed, and then stimulated with proinflammatory ones and vice versa. The present study revealed a novel function for MSX3 to enhance the M2 polarization of microglia through the direct gene induction of known M2 key transcription factors. The mRNA expression of these M1/M2 molecules paralleled with the dynamic of this M1/M2 macrophage/microglia population in the development of OIR (fig. However, the molecular mechanism is unclear. The SOD1-mutant microglia isolated from mice with early-stage ALS express higher levels of M2 microglia phenotype markers and lower levels of pro-inflammatory microglia markers, compared with the SOD1-mutant microglia isolated from mice with end-stage ALS . Fasudil-conditioned microglia medium promoted a neuroprotective effect against PC12 neurons, suggesting that fasudil-induced M2 microglia contribute to the survival of neurons. Labeled cells are represented by the black shaded populations, whereas unlabeled cells are depicted by the grey line (%: % of cells in M1 or M2 region, MFI: mean fluorescence intensity). 39 Following TBI M1 microglia is rapidly induced and maintained at the site of the injury, whereas M2 microglia is transiently expressed after injury. In MS patients, M1 microglia were present in a variety of lesions, whereas M2 microglia appear only in acute lesions and the active Activated microglia have two functional states (M1 and M2) which play dual roles in neurodegenerative diseases. The polarization of microglia has been described as a functional dichotomy: classical (M1, proinflammatory) and alternative (M2, anti-inflammatory) activation. Keywords: alternative activation, M2, microglia, neuroinflammation Background For the better part of a century, the function of microglia in the central nervous system (CNS) was a topic wrapped in controversy. has been shown that M1 microglia promote secondary brain damage, whilst M2 microglia facilitate recovery following stroke. Although microglial activation is often considered neurotoxic, microglia are essential defenders against many neurodegenerative diseases. These results indicate a new treatment option whereby fasudil inhibits the inflammatory response by controlling a helpful polarization in microglia/macrophages. Following TBI, microglia of the M1 phenotype increased significantly, while those of the M2 phenotype decreased. To further investigate the function of Hv1 proton channel in regulating microglial polarity, we used primary cultured microglia and directly induced M1/M2 polarization in vitro. Additionally, in vivo human studies, informed by animal models, will help better characterize the role of microglia activation in the dynamic stages of the disease. Particular attention is given to utilizing M2 microglial polarization as a potential therapeutic option in treating diseases. In the activated form, microglia are traditionally divided into two states: M1 (classical), and M2 (alternative), depending on the nature of the stimulus (5). However, the alternative M2 type of microglia have an anti-inflammatory phenotype, which promote tissue remodeling and repair and angiogenesis via the release of anti-inflammatory cytokines such as IL-4, and IL-10 and diminished levels of pro-inflammatory cytokines. Results: We demonstrated that compared to resting and classically activated (M1) human microg-lia, P2Y12 expression is increased under alternatively activated (M2) conditions. A shift to an M2 phenotype of activated microglia has been correlated with neuroprotection, recovery, and repair in various disease settings [25–27]. Activated microglia can be divided into M1 and M2 subgroups. It also seems increasingly likely that microglial dysfunction can underlie … There are three types of M2 macrophages: M2a, M2b, and M2c. The BBB consists of endothelial cells surrounded by astrocytes. Furthermore, the expression of a limited number of M2‐related genes cannot reliably describe the complete function of microglia. These cells provide immune surveillance and are mobilized in response to disparate diseases and injuries. We previously found that naringenin, a blood–brain barrier penetrating compound, decreased Aβ deposits and recovers memory function in transgenic AD model mice. M2 microglia play important roles in anti‐inflammatory effects, Aβ clearance, and memory recovery in AD. In the present study, we explored a possible neuroprotective function of M2 microglia against kainic acid (KA)-induced neurodegeneration in primary neurons co-cultured with different microglial populations. The expression of M1 markers (iNOS and CD16) was significantly increased by LPS plus IFN-γ stimulation. Microglia were isolated and left in culture for 24 hours. However, we prefer here using the broader pro- … Therefore, this review aimed S8). M1 microglia worsen BBB disruption, while M2 microglia assist in repairing BBB damage. In view of the protective function of the M2 phenotype, numerous researches have focused on the M2-polarized microglia for the treatment of cerebral ischemia. This process, which is one of the quintessential defining functions of M2 polarized cells, seems to be a default function for microglia. An even smaller number of molecules, such as Ym1 or Arg1, are often chosen to identify M2 cells in many studies; yet, how these molecules functionally contribute to neuroprotection remains to be established. Metabolism under polarization states Increasing evidence suggests a role of metabolic reprogramming in the regulation of the innate inflammatory response. In response to ADP, the endogenous ligand of P2Y12, M2 microglia have increased ligand-mediated calcium 16 M1 microglia produce proinflammatory cytokines such as IL-1β and TNF-α and induce NO synthase activity. and demonstrated that microglia expressed the M2-associated protein Ym1 (now known as CHIL3) in an IL4 dependent manner (Ponomarev et al., 2007). The concept of microglia polarization was first explored in the murine system by Ponomarev et al. 15 M1 microglia promote inflammation and oligodendrocyte damage, whereas M2 microglia regulate immune functions and promote repair in inflammatory diseases of the CNS. ing M2 polarized microglia into the CNS promotes recovery [11–13]. These macrophages are associated with wound healing and tissue repair. These CD86 + CD206 + macrophages/microglia also highly expressed other M1/M2 molecules such as CD80, CD163, Il1b, and Arg1 (fig. 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