scholarly journals Microglial Polarization and Inflammatory Mediators After Intracerebral Hemorrhage

2016 ◽  
Vol 54 (3) ◽  
pp. 1874-1886 ◽  
Author(s):  
Zhen Zhang ◽  
Ze Zhang ◽  
Hong Lu ◽  
Qingwu Yang ◽  
He Wu ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Inflammatory Mediators ◽  
Microglial Polarization

scholarly journals Intracerebral Pro-inflammatory Cytokine Increase in Surgically Evacuated Intracerebral Hemorrhage - an Observational Microdialysis Study

2021 ◽  
Author(s):  
Lovisa Tobieson ◽  
Anna Gard ◽  
Karsten Ruscher ◽  
Niklas Marklund
Keyword(s):  
Intracerebral Hemorrhage ◽  
Brain Tissue ◽  
Inflammatory Cytokines ◽  
Inflammatory Mediators ◽  
Inflammatory Cytokine ◽  
Tissue Injury ◽  
Treatment Options ◽  
Cerebral Microdialysis ◽  
Cytokines And Chemokines ◽  
Anti Inflammatory

Abstract Background: Treatment options for spontaneous intracerebral hemorrhage (ICH) are limited. A possible inflammatory response in the brain tissue surrounding an ICH may exacerbate the initial injury and could be a target for treatment. Methods: In this observational study, ten patients needing surgical evacuation of supratentorial ICH received two cerebral microdialysis (MD) catheters; one in the perihemorrhagic zone (PHZ), and one in non-eloquent cortex (SNX) remote from the ICH. The microdialysate was analysed for energy metabolites (including lactate/pyruvate ratio (LPR) and glucose) and for inflammatory mediators using a multiplex immunoassay of 27 cytokines and chemokines at 6-10 hours, 20-26 hours and 44-50 hours after surgery. Results: Deranged energy metabolic markers suggestive of a metabolic crisis were found in PHZ compared to SNX, persistent throughout the 50 hours. Pro-inflammatory cytokines IL-8, TNF-α, IL-2, IL-1β, IL-6 and IFN-γ, anti-inflammatory cytokine IL-13, IL-4, and VEGF-A were significantly higher in PHZ compared to SNX, most prominent at 20-26 hours following ICH evacuation.Conclusions: Higher levels of pro- and anti-inflammatory cytokines in the perihemorrhagic brain tissue suggests a role for inflammatory mediators involved in secondary injury cascades potentially exacerbating tissue injury, which may constitute a target for future medical interventions.

scholarly journals Intracerebral Proinflammatory Cytokine Increase in Surgically Evacuated Intracerebral Hemorrhage: A Microdialysis Study

2021 ◽  
Author(s):  
Lovisa Tobieson ◽  
Anna Gard ◽  
Karsten Ruscher ◽  
Niklas Marklund
Keyword(s):  
Intracerebral Hemorrhage ◽  
Brain Tissue ◽  
Inflammatory Mediators ◽  
Treatment Options ◽  
Interferon Γ ◽  
Cerebral Microdialysis ◽  
Secondary Brain Injury ◽  
Study Objective ◽  
Surgical Evacuation ◽  
Anti Inflammatory

Abstract Background Treatment options for spontaneous intracerebral hemorrhage (ICH) are limited. A possible inflammatory response in the brain tissue surrounding an ICH may exacerbate the initial injury and could be a target for treatment of subsequent secondary brain injury. The study objective was to compare levels of inflammatory mediators in the interstitial fluid of the perihemorrhagic zone (PHZ) and in seemingly normal cortex (SNX) in the acute phase after surgical evacuation of ICH, with the hypothesis being that a difference could be demonstrated between the PHZ and the SNX. Methods In this observational study, ten patients needing surgical evacuation of supratentorial ICH received two cerebral microdialysis catheters: one in the PHZ and one in the SNX that is remote from the ICH. The microdialysate was analyzed for energy metabolites (including lactate pyruvate ratio and glucose) and for inflammatory mediators by using a multiplex immunoassay of 27 cytokines and chemokines at 6–10 h, 20–26 h, and 44–50 h after surgery. Results A metabolic crisis, indicated by altered energy metabolic markers, that persisted throughout the observation period was observed in the PHZ when compared with the SNX. Proinflammatory cytokines interleukin (IL) 8, tumor necrosis factor α, IL-2, IL-1β, IL-6 and interferon γ, anti-inflammatory cytokine IL-13, IL-4, and vascular endothelial growth factor A were significantly higher in PHZ compared with SNX and were most prominent at 20–26 h following ICH evacuation. Conclusions Higher levels of both proinflammatory and anti-inflammatory cytokines in the perihemorrhagic brain tissue implies a complex role for inflammatory mediators in the secondary injury cascades following ICH surgery, suggesting a need for targeted pharmacological interventions.

scholarly journals Minocycline promotes posthemorrhagic neurogenesis via M2 microglia polarization via upregulation of the TrkB/BDNF pathway in rats

2018 ◽  
Vol 120 (3) ◽  
pp. 1307-1317 ◽  
Author(s):  
Hongsheng Miao ◽  
Runming Li ◽  
Cong Han ◽  
Xiuzhen Lu ◽  
Hang Zhang
Keyword(s):  
Intracerebral Hemorrhage ◽  
Therapeutic Potential ◽  
Autologous Blood ◽  
Neurological Deficits ◽  
Neuroprotective Effects ◽  
Microglial Polarization ◽  
Arginase 1 ◽  
M2 Microglia ◽  
Microglia Polarization ◽  
Bdnf Pathway

Intracerebral hemorrhage (ICH) is a devastating disease worldwide with increasing mortality. The present study investigated whether minocycline was neuroprotective and induced M2 microglial polarization via upregulation of the TrkB/BDNF pathway after ICH. ICH was induced via injection of autologous blood into 150 Sprague-Dawley rats. A selective TrkB antagonist [N2–2-2-oxoazepan-3-yl amino] carbonyl phenyl benzo (b) thiophene-2-carboxamide (ANA 12)] and agonist [ N-[2-(5-hydroxy-1H-indol-3-yl) ethyl]-2-oxopiperidine-3-carboxamide (HIOC)] were used to investigate the mechanism of minocycline-induced neuroprotection. Minocycline improved ICH-induced neurological deficits and reduced M1 microglia marker protein (CD68, CD16) expression as well as M2 microglial polarization (CD206 and arginase 1 protein). Minocycline administration enhanced microglia-neuron cross talk and promoted the proliferation of neuronal progenitor cells, such as DCX- and Tuj-1-positive cells, 24 h after ICH. Minocycline also increased M2 microglia-derived brain-derived neurotrophic factors (BDNF) and the upstream TrkB pathway. ANA 12 reversed the neuroprotective effects of minocycline. HIOC exhibited the same effects as minocycline and accelerated neurogenesis after ICH. This study demonstrated for the first time that minocycline promoted M2 microglia polarization via upregulation of the TrkB/BDNF pathway and promoted neurogenesis after ICH. This study contributes to our understanding of the therapeutic potential of minocycline in ICH. NEW & NOTEWORTHY The present study gives several novel points: 1) Minocycline promotes neurogenesis after intracerebral hemorrhage in rats. 2) Minocycline induces activated M1 microglia into M2 neurotrophic phenotype. 3) M2 microglia secreting BDNF remodel the damaged neurocircuit.

scholarly journals Melatonin reduces neuroinflammation and improves axonal hypomyelination by modulating M1/M2 microglia polarization via JAK2-STAT3-telomerase pathway in postnatal rats exposed to lipopolysaccharide

2021 ◽  
Author(s):  
Qiuping Zhou ◽  
Lanfen Lin ◽  
Haiyan Li ◽  
Shuqi Jiang ◽  
Huifang Wang ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Periventricular White Matter ◽  
Microglial Polarization ◽  
Proinflammatory Mediators ◽  
M2 Microglia ◽  
Microglia Polarization ◽  
M1 Phenotype ◽  
Anti Inflammatory ◽  
Postnatal Rats

Abstract Microglia activation and associated inflammation are implicated in the periventricular white matter damage (PWMD) in septic postnatal rats. This study investigated whether melatonin would mitigate inflammation and alleviate the axonal hypomyelination in the corpus callosum in septic postnatal rats. We further explored if this might be through modulating microglial polarization from M1 phenotype to M2 through JAK2/STAT3/telomerase pathway. We reported here that melatonin, indeed, not only can it reduce the neurobehavioral disturbances in LPS injected rats, but it can also dampen microglia mediated inflammation. Thus, in LPS + melatonin group, expression of proinflammatory mediators in M1 phenotype microglia was downregulated. As opposed to this, M2 microglia were increased which was accompanied by upregulated expression of anti-inflammatory mediators along with TERT or MT1. In parallel to this was decreased NG2 expression but increased expression of myelin and neurofilament proteins. That melatonin can improve hypomyelination was confirmed by electron microscopy. In vitro in primary microglia stimulated by LPS, melatonin decreased the expression of proinflammatory mediators significantly; but it increased expression of anti-inflammatory mediators. Additionally, the expression levels of p-JAK2 and p-STAT3 were significantly elevated in microglia after melatonin treatment. Remarkably, the melatonin effects on LPS treated microglia was blocked by melatonin receptor, JAK2, STAT3 and telomerase reverse transcriptase inhibitors, respectively. Taken together, it is concluded that melatonin can attenuate PWMD through shifting M1 microglia towards M2 via MT1/JAK2/STAT3/telomerase pathway. The results suggest a new therapeutic strategy whereby melatonin may be adopted to convert microglial polarization that would ultimately contribute to attenuation of PWMD.

Abstract 114: CX3CR1-null Microglia Fail to Transition to an M2 Phenotype after Intracerebral Hemorrhage

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Roslyn A Taylor ◽  
Matthew D Hammond ◽  
Youxi Ai ◽  
Lauren H Sansing
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Intracerebral Hemorrhage ◽  
Microglial Polarization ◽  
Arginase 1 ◽  
The Right ◽  
Bone Marrow Chimeras ◽  
Receptor Cx3cr1 ◽  
M2 Phenotype

Introduction: Intracerebral hemorrhage (ICH) results in the activation of microglia. Microglia can polarize into either a pro-inflammatory (M1), or a reparative (M2) phenotype; the effect of microglial polarization after ICH is unknown. Microglia express the chemokine receptor CX3CR1, which has been shown to regulate microglial neurotoxicity. CX3CR1 +/GFP mice have a functional CX3CR1 and are frequently used to identify microglia. We previously reported that mice with CX3CR1-null microglia do not show functional recovery 14 days after ICH. We hypothesize that 1) microglia transition from M1 to M2 phenotypes in the acute to subacute period after ICH and 2) CX3CR1-null microglia fail to make this transition, inhibiting recovery after ICH. Methods: ICH was modeled by injecting 20ul of WT blood into the right striatum. Microglia were sorted from male CX3CR1 +/GFP mice 0.5, 1, 3, 7, and 14 days after ICH in order to specifically study microglia phenotypes. RNA was extracted and qRT-PCR was performed to analyze changes in gene expression. To study microglial CX3CR1 function, C57BL/6 (WT) and CX3CR1 GFP/GFP (CX3CR1-null) mice were irradiated and reconstituted with WT bone marrow (CD45.1) to generate bone marrow chimeras (CD45.1->WT or CD45.1->CX3CR1-null). Brains were harvested for flow cytometry 14 days after ICH. Results: At 12 hours after ICH, microglia have high IL-6 gene expression (M1). However, M2 markers arginase-1, TGF-β and SOCS3 increase over time (Fig. 1), suggesting microglia transition from M1 to M2 over the first 2 weeks after ICH. By flow cytometry, CX3CR1-null microglia had significantly less SIRPα, a receptor involved in phagocytosis of erythrocytes, and CD206, an M2 marker, than WT microglia 14 days after ICH. Conclusions: Our data show WT microglia transition from an M1 to an M2 phenotype after ICH. Our results also suggest microglial CX3CR1 is necessary for transition toward an M2 phenotype after ICH and this transition is required for recovery after ICH.

scholarly journals Melatonin Reduces Neuroinflammation and Improves Axonal Hypomyelination by Modulating M1/M2 Microglia Polarization via JAK2-STAT3-Telomerase Pathway in Postnatal Rats Exposed to Lipopolysaccharide

2021 ◽  
Author(s):  
Qiuping Zhou ◽  
Lanfen Lin ◽  
Haiyan Li ◽  
Huifang Wang ◽  
Shuqi Jiang ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Inflammatory Mediators ◽  
Telomerase Reverse Transcriptase ◽  
Melatonin Receptor ◽  
Microglial Polarization ◽  
Proinflammatory Mediators ◽  
M2 Microglia ◽  
M1 Phenotype ◽  
Anti Inflammatory ◽  
Postnatal Rats

AbstractMicroglia activation and associated inflammation are implicated in the periventricular white matter damage (PWMD) in septic postnatal rats. This study investigated whether melatonin would mitigate inflammation and alleviate the axonal hypomyelination in the corpus callosum in septic postnatal rats. We further explored if this might be related to the modulation of microglial polarization from M1 phenotype to M2 through the JAK2/STAT3/telomerase pathway. We reported here that indeed melatonin not only can it reduce the neurobehavioral disturbances in LPS-injected rats, but it can also dampen microglia-mediated inflammation. Thus, in LPS + melatonin group, the expression of proinflammatory mediators in M1 phenotype microglia was downregulated. As opposed to this, M2 microglia were increased which was accompanied by upregulated expression of anti-inflammatory mediators along with telomerase reverse transcriptase or melatonin receptor 1(MT1). In parallel to this was decreased NG2 expression but increased expression of myelin and neurofilament proteins. Melatonin can improve hypomyelination which was confirmed by electron microscopy. In vitro in primary microglia stimulated by LPS, melatonin decreased the expression of proinflammatory mediators significantly; but it increased the expression of anti-inflammatory mediators. Additionally, the expression levels of p-JAK2 and p-STAT3 were significantly elevated in microglia after melatonin treatment. Remarkably, the effect of melatonin on LPS-treated microglia was blocked by melatonin receptor, JAK2, STAT3 and telomerase reverse transcriptase inhibitors, respectively. Taken together, it is concluded that melatonin can attenuate PWMD through shifting M1 microglia towards M2 via MT1/JAK2/STAT3/telomerase pathway. The results suggest a new therapeutic strategy whereby melatonin may be adopted to convert microglial polarization from M1 to M2 phenotype that would ultimately contribute to the attenuation of PWMD.

scholarly journals Berberine exhibits neuroprotective effects through inhibited autophagy and promoted microglial M1 transferred to M2 polarization

2020 ◽  
Author(s):  
Qiang Lei ◽  
Zhiping Hu ◽  
Binbin Yang ◽  
Zheng Jiang ◽  
Fangfang Zhou
Keyword(s):  
Intracerebral Hemorrhage ◽  
Neuroprotective Effect ◽  
Neurological Deficits ◽  
Current Evidence ◽  
Secondary Injury ◽  
Neuroprotective Effects ◽  
Neurological Outcomes ◽  
Microglial Polarization ◽  
The Brain ◽  
M1 Type

Abstract Background: Intracerebral haemorrhage (ICH) induces autophagy excessive activation and microglia mainly switched into proinflammatory M1 type, which can cause severe secondary injury. Current evidence has implied that berberine has a protective effect against ischaemic stroke through mediated autophagy and microglial polarization. However, the neuroprotective effect of berberine in intracerebral hemorrhage (ICH) remains unclear.Method: In this study the effect of berberine on rats model of intracerebral hemorrhage were investigated through Immunofluorescence, qPCR, ELISA, and western blot.Result: Berberine administration significantly reduces neurological deficits and the brain water content via inhibited autophagy, promoted M1 type microglia to M2 type, and subsequently exerts anti-inflammation effects in a rat model of ICH.Conclusion: These results suggest that berberine reduced secondary injury and improved neurological outcomes in ICH model.

scholarly journals Fingolimod alters inflammatory mediators and vascular permeability in intracerebral hemorrhage

2015 ◽  
Vol 31 (6) ◽  
pp. 755-762 ◽  
Author(s):  
Yu-Jing Li ◽  
Guo-Qiang Chang ◽  
Yuanchu Liu ◽  
Ye Gong ◽  
Chunsheng Yang ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Vascular Permeability ◽  
Inflammatory Mediators
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