Effects of SC99 on cerebral ischemia-perfusion injury in rats: Selective modulation of microglia polarization to M2 phenotype via inhibiting JAK2-STAT3 pathway

Ding, Yiping; Qian, Jinhong; Li, Haiying; Shen, Haitao; Li, Xiang; Kong, Yan; Xu, Zai‐Quan; Chen, Gang

doi:10.1016/j.neures.2018.05.002

Cited by 26 publications

(19 citation statements)

References 46 publications

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“…In hypoxia-activated BV2 microglia, the phosphorylation levels of STAT1 were significantly increased, which was accompanied by increased expression levels of M1 microglia markers, such as cluster of differentiation 68 and iNOS (70); however, the expression levels of these markers were significantly decreased in STAT1 -/-BV2 cells following hypoxia. Several previous studies have also identified that STaT3 is also associated with the regulation of M1 microglia polarization in both an Mcao-induced and a bilateral common carotid arteries stenosis (BcaS)-induced model of ischemic stroke (19,(71)(72)(73). ding et al (72) identified that the inhibition of the Janus kinase 2 (JaK2)/STaT3 signaling pathway promoted the transition from resting microglia to the M2 phenotype to exert anti-inflammatory effects; briefly, the phosphorylation levels of JaK2 and STaT3 were increased in the acute phase of cerebral ischemia in the mice, which was Figure 1.…”

Section: Nf-κbmentioning

confidence: 99%

“…Several previous studies have also identified that STaT3 is also associated with the regulation of M1 microglia polarization in both an Mcao-induced and a bilateral common carotid arteries stenosis (BcaS)-induced model of ischemic stroke (19,(71)(72)(73). ding et al (72) identified that the inhibition of the Janus kinase 2 (JaK2)/STaT3 signaling pathway promoted the transition from resting microglia to the M2 phenotype to exert anti-inflammatory effects; briefly, the phosphorylation levels of JaK2 and STaT3 were increased in the acute phase of cerebral ischemia in the mice, which was Figure 1. dynamic changes in microglia marker levels over time following iS.…”

Section: Nf-κbmentioning

confidence: 99%

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

et al. 2020

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ischemic stroke is one of the leading causes of mortality and disability worldwide. However, there is a current lack of effective therapies available. as the resident macrophages of the brain, microglia can monitor the microenvironment and initiate immune responses. in response to various brain injuries, such as ischemic stroke, microglia are activated and polarized into the proinflammatory M1 phenotype or the anti-inflammatory M2 phenotype. The immunomodulatory molecules, such as cytokines and chemokines, generated by these microglia are closely associated with secondary brain damage or repair, respectively, following ischemic stroke. it has been shown that M1 microglia promote secondary brain damage, whilst M2 microglia facilitate recovery following stroke. in addition, autophagy is also reportedly involved in the pathology of ischemic stroke through regulating the activation and function of microglia. Therefore, this review aimed to provide a comprehensive overview of microglia activation, their functions and changes, and the modulators of these processes, including transcription factors, membrane receptors, ion channel proteins and genes, in ischemic stroke. The effects of autophagy on microglia polarization in ischemic stroke were also reviewed. Finally, future research areas of ischemic stroke and the implications of the current knowledge for the development of novel therapeutics for ischemic stroke were identified. Contents 1. introduction 2. Microglia 3. Modulatory mechanisms of microglia polarization 4. autophagy 5. conclusions

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Section: Nf-κbmentioning

confidence: 99%

Section: Nf-κbmentioning

confidence: 99%

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

et al. 2020

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“…[10][11][12] Suppression of STAT3 signalling pathway activation decreases the infarct volume, number of apoptotic cells and restores the neurological deficits in ischaemic stroke. 13 14 Recent studies imply that STAT3/Janus kinase-signal transducer 2 (JAK2) signalling pathway participates in the microglia-dependent neuroinflammatory responses, and this participation may relate Open access to the modulation of the microglial polarisation. 8 13 In SAH, activation of the STAT3/JAK2 signalling pathway contributes to early brain injury, cerebral vasculopathy and neurological deficit.…”

Section: Introductionmentioning

confidence: 99%

Novel role of STAT3 in microglia-dependent neuroinflammation after experimental subarachnoid haemorrhage

et al. 2021

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Background and purposeSignal transducer and activator of transcription 3 (STAT3) may contribute to the proinflammation in the central nervous system diseases by modulating the microglial responses. Thus, this study was intended to investigate the effect of STAT3 on microglia-dependent neuroinflammation and functional outcome after experimental subarachnoid haemorrhage (SAH).MethodsThe SAH model was established by endovascular perforation in the mouse. Real-time PCR (RtPCR) and western blot were used to examine the dynamic STAT3 signalling pathway responses after SAH. To clarify the role of the STAT3 signalling pathway in the microglia-dependent neuroinflammation after SAH, the microglia-specific STAT3 knockout (KO) mice were generated by the Cre-LoxP system. The neurological functions were assessed by Catwalk and Morris water maze tests. Neuronal loss after SAH was determined by immunohistochemistry staining. Microglial polarisation status after STAT3 KO was then examined by RtPCR and immunofluorescence.ResultsThe STAT3 and Janus kinase-signal transducer 2 activated immediately with the upregulation and phosphorylation after SAH. Downstream factors and related mediators altered dynamically and accordingly. Microglial STAT3 deletion ameliorated the neurological impairment and alleviated the early neuronal loss after SAH. To investigate the underlying mechanism, we examined the microglial reaction after STAT3 KO. STAT3 deletion reversed the increase of microglia after SAH. Loss of STAT3 triggered the early morphological changes of microglia and primed microglia from M1 to M2 polarisation. Functionally, microglial STAT3 deletion suppressed the SAH-induced proinflammation and promoted the anti-inflammation in the early phase.ConclusionsSTAT3 is closely related to the microglial polarisation transition and modulation of microglia-dependent neuroinflammation. Microglial STAT3 deletion improved neurological function and neuronal survival probably through promoting M2 polarisation and anti-inflammatory responses after SAH. STAT3 may serve as a promising therapeutic target to alleviate early brain injury after SAH.

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“…For example, the activation and phosphorylation of STAT1 is associated with M1 microglia activation in hypoxia-activated BV2 cells, and acts as the increased expression levels of M1 microglia ( 114 ). Furthermore, STAT3 was also associated with M1 microglia polarization in both an MCAO-induced and a bilateral common carotid arteries stenosis (BcaS)-induced model of ischemic stroke ( 115 , 116 ). The results discussed above reveal the regulatory role of STAT on the inflammatory response after stroke.…”

Section: Mechanisms Of Microglial Activation and Polarization After Strokementioning

confidence: 99%

Effects of Microglial Activation and Polarization on Brain Injury After Stroke

et al. 2021

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Stroke is one of the most common causes of death worldwide. The subsequent development of neuroinflammation and brain edema dramatically increases the risks associated with stroke, leading to a substantial increase in mortality. Although considerable progress has been made in improving cerebral perfusion in the acute phase of stroke, effective treatment options for the subacute and chronic phases associated with cerebral infarction are limited. Microglia, the innate immune cells of the central nervous system (CNS), can be activated and polarized to take on different phenotypes in response to stimulations associated with stroke, including pro-inflammatory and anti-inflammatory phenotypes, which affect the prognosis of stroke. Therefore, investigation of the activation and polarizing mechanisms of microglia plays a critical role in treating stroke. The aim of this article was to investigate the significance of microglial phenotype regulation in stroke treatment by summarizing the activation, polarizing mechanisms, and general microglia characteristics.

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Effects of SC99 on cerebral ischemia-perfusion injury in rats: Selective modulation of microglia polarization to M2 phenotype via inhibiting JAK2-STAT3 pathway

Cited by 26 publications

References 46 publications

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

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

Novel role of STAT3 in microglia-dependent neuroinflammation after experimental subarachnoid haemorrhage

Effects of Microglial Activation and Polarization on Brain Injury After Stroke

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