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microglia activation in the offspring of prenatal Poly I:C exposed rats:a PET imaging and immunohistochemistry study

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General Psychiatry 2018年第4期31卷 31-38页

作者： Xue Li Xin Tian Luxian Lv Gangrui Hei Xufeng Huang Xiaoduo Fan Jinming Zhang Jianjiang Zhang Lijuan Pang Xueqin Song Department of Nuclear Medicine Chinese PLA General HospitalBeijingChina The First Affliated Hospital/Zhengzhou UniversityZhengzhouChina Henan Province Biological Psychiatry Key Laboratory Xinxiang Medical UniversityXinxiangChina Henan Province Mental Hospital The Second Affliated HospitalXinxiang Medical UniversityXinxiangChina School of Medicine and IHMRI University of WollongongWollongongNew South WalesAustralia UMass Memorial Medical Center University of Massachusetts Medical SchoolWorcesterMassachusettsUSA Department of Nuclear Medicine Chinese PLA General HospitalBeijingChina

Background The well-known ‘pyrotherapy’ of Julius Wagner-Jauregg might be the beginning of the study on the immunological concepts of schizophrenia. As the primary immune effector cells in the brain, microglia play a pivotal role in neuroinfammatory processes. Maternal viral infection during pregnancy is associated with an increased risk for psychiatric disorders with presumed neurodevelopmental origin, including autism spectrum disorders and schizophrenia. The present study was to quantify microglia activation in vivo in the mature offspring of rats exposed to polyriboinosinic–polyribocytidilicacid （Poly I：C） during pregnancy using ^11C-PK11195 positron emission tomography （PET） and *** The study aimed to quantify microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I：C exposed *** Offspring of Poly I：C-treated dams were the model group, offspring of saline-treated dams were the control group. Behavioural test for two groups was taken by spontaneous activity, prepulse inhibition （PPI） and latent inhibition （LI） test （including active avoidance conditioning task and passive avoidance conditioning task）. Randomly selected successful model rats were assessed by behavioural test in the model group and control group rats. 11C-PK11195 micro-PET/CT and immunohistochemistry were performed on the selected rats to measure microglia *** The treatment group showed hyperlocomotion and defcits in PPI and LI compared with the control group. The treatment group also showed an increased 11C-PK11195 uptake ratio in the prefrontal cortex （t=-3.990, p=0.003） and hippocampus （t=-4.462, p=0.001）. The number of activated microglia cells was signifcantly higher in the treatment group than in the control group （hippocampus： t=8.204, p〈0.001; prefrontal： t=6.995, p〈0.001）. Within the treatment group, there were signifcant correlations between the behavioural parameters and the activa

关键词： microglia activation the offspring of prenatal Poly I C exposed rats a PET imaging and immunohistochemistry study

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microglia activation-induced mesencephalic dopaminergic neurodegeneration -- an in vitro model for Parkinson＇s disease

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Frontiers of physics 2012年第5期7卷 404-411页

作者： Bin KING Guoying BING Sanders-Brown Center on Aging University of Kentucky Lexington KY 40536 USA Department of Anatomy and Neurobiology University of Kentucky Lexington KY 40536 USA

Uncontrolled and chronic microglia activation has been implicated in the process of dopaminergic neuron degeneration in sporadic Parkinson＇s disease （PD）. Elevated proinflammatory mediators, presumably from activated microglia （e.g., cytokines, PGE2, nitric oxide, and superoxide radical）, have been observed in PD patients and are accompanied by dopaminergic neuronal loss. Preclinical studies have demonstrated the deleterious effects of proinflammatory mediators in various in vivo and in vitro models of PD. The use of in vitro studies provides a unique tool to investigate the interaction between neurons and microglia and is especially valuable when considering the role of activated microglia in neuronal death. Here we summarize findings highlighting the potential mechanisms of microglia- mediated neurodegeneration in PD.

关键词： dopaminergic neurons microglia activation nitric oxide cytokines PGE2 p3 8 MAPK

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Houttuynia cordata Thunb rescues retinal ganglion cells through inhibiting microglia activation in a rat model of retinal ischemia-reperfusion

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International Journal of Ophthalmology(English edition) 2020年第12期13卷 1880-1886页

作者： Le-Meng Ren Ying-Hui Zhang The First Clinical Medical College Lanzhou UniversityLanzhou 730000Gansu ProvinceChina Medical Record Room the Second Hospital of Shandong UniversityShandong UniversityJinan 250033Shandong ProvinceChina

AIM:To determine whether Houttuynia cordata Thunb(HCT)can increase the survival of the retinal ganglion cells(RGCs)and inhibit microglia activation following retinal ischemia-reperfusion(RIR)***:Rat model of RIR was induced by transient elevation of the intraocular pressure(IOP).HCT was orally administered for 2 d before the performance of retinal RIR model and once a day for the next 14 *** 14 d of RIR injury,the rats were sacrificed for further *** RGCs were stained with haematoxylin and eosin(H&E).Apoptosis of RGCs was detected by TUNEL *** function was examined by flash-electroretinography(F-ERG).Retinal microglia were labeled using Iba-1,one specific marker for *** m RNA expression levels of inducible nitric oxide synthase(i NOS),tumor necrosis factor alpha(TNF-α),and interleukin 1 beta(IL-1β)were assessed by quantitative real time reverse transcription polymerase chain reaction(q RT-PCR).RESULTS:Systemic HCT treatment significantly reduced RGCs death by H&E staining and exhibited an anti-apoptotic effect as assessed by TUNEL staining at day 14 after RIR *** greatly improved the retinal function as examined by *** number of activated microglia significantly increased after RIR injury,which was significantly attenuated by HCT ***,RIR injury induced a strong upregulation of pro-inflammatory genes TNF-α,i NOS and IL-1βm RNAs at day 14 post injury,which was suppressed by ***:Neuroprotective effects of HCT encourage the survival of RGCs through inhibiting microglia activation due to RIR *** these results support the use of HCT as promising therapy for the ischemic events of the retina diseases.

关键词： Houttuynia cordata Thunb retinal ganglion cell microglia activation retinal ischemia-reperfusion

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Role of brain mast cell in inducing microglia activation

Role of brain mast cell in inducing microglia activation

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第十届全国免疫学学术大会

作者： Shu Zhang Hongquan Dong Xiang Zhang Yiming Wang Xiqiao Zhou Clinical Research Center the First Affiliated Hospi tal of Nanjing Medical University Department of Anesthesiology the First Affiliated Hospital of Nanjing Medical University Department of Gastroenterology the First Affiliated Hospital of Nanjing Medical University

Background:Brain mast cells in CNS disorders are activated,which induce release of several ***,the influence of mast cells activation on microglia,the resident immune cells in the brain,remains ***:Induction of microglia activation by mast cells was examined with the addition of conditioned medium from HMC-1 to primary cultured *** activation of mast cells was determined by flow cytometry *** activated microglia was determined by immunofluorescence and flow cytometry ***,tryptase,TNF-alpha and IL-6 were measured with a commercial ELISA *** MAPK and AKT phosphorylation were evaluated by Western ***:In the present study,we found that CRH could induce HMC-1 activation and release of various *** conditioned medium from activated HMC-1 could stimulate microglia activation and subsequent production of pro-inflammatory factors TNF-αand *** antagonists of H1R,H4R,PAR2 and TNFR1 reduced HMC-1-induced TNF-alpha and IL-6 production and MAPK and PI3K/AKT pathway *** the other hand,inhibitors of JNK,p38,ERK or PI3K suppressed HMC-1-induced TNF-alpha and IL-6 release from ***:These results implicate that mediators released from mast cells could trigger microglial activation,and interactions between mast cells and microglia could constitute a new and unique therapeutic target for CNS immune inflammation-related diseases.

关键词： microglia activation HMC-1 MAPK PI3K/AKT CNS immune inflammation

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Orchestration of antiviral responses within the infected central nervous system

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Cellular & Molecular Immunology 2024年第9期21卷 943-958页

作者： Andreas Pavlou Felix Mulenge Olivia Luise Gern Lena Mareike Busker Elisabeth Greimel Inken Waltl Ulrich Kalinke Institute for Experimental Infection Research TWINCORECentre for Experimental and Clinical Infection Researcha joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School30625HannoverGermany Department of Pathology University of Veterinary Medicine HannoverFoundation30559HannoverGermany Cluster of Excellence RESIST(EXC 2155) Hannover Medical School30625HannoverGermany

Many newly emerging and re-emerging viruses have neuroinvasive potential,underscoring viral encephalitis as a global research *** entry of the virus into the CNS,severe neurological life-threatening conditions may manifest that are associated with high morbidity and *** currently available therapeutic arsenal against viral encephalitis is rather limited,emphasizing the need to better understand the conditions of local antiviral immunity within the infected *** this review,we discuss new insights into the pathophysiology of viral encephalitis,with a focus on myeloid cells and CD8^(+)T cells,which critically contribute to protection against viral CNS *** illuminating the prerequisites of myeloid and T cell activation,discussing new discoveries regarding their transcriptional signatures,and dissecting the mechanisms of their recruitment to sites of viral replication within the CNS,we aim to further delineate the complexity of antiviral responses within the infected ***,we summarize the current knowledge in the field of virus infection and neurodegeneration and discuss the potential links of some neurotropic viruses with certain pathological hallmarks observed in neurodegeneration.

关键词： Virus infection Virus control within the brain T cell recruitment to the brain microglia activation

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Rutin pretreatment promotes microglial M1 to M2 phenotype polarization

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Neural Regeneration Research 2021年第12期16卷 2499-2504页

作者： Guang-Ping Lang Can Li Ying-Ying Han Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education Zunyi Medical UniversityZunyiGuizhou ProvinceChina Special Key Laboratory of Oral Diseases Research Higher Education Institutions of Guizhou ProvinceZunyi Medical UniversityZunyiGuizhou ProvinceChina

microglial cells are important resident innate immune components in the central nervous system that are often activated during *** microglia can display one of two phenotypes,M1 or M2,which each play distinct roles in ***,a dietary flavonoid,exhibits protective effects against ***,whether rutin is able to influence the M1/M2 polarization of microglia remains *** this study,in vitro BV-2 cell models of neuroinflammation were established using 100 ng/mL lipopolysaccharide to investigate the effects of 1-hour rutin pretreatment on microglial *** results revealed that rutin pretreatment reduced the expression of the proinflammatory cytokines tumor necrosis factor-α,interleukin-1β,and interleukin-6 and increased the secretion of *** pretreatment also downregulated the expression of the M1 microglial markers CD86 and inducible nitric oxide synthase and upregulated the expression of the M2 microglial markers arginase 1 and *** pretreatment inhibited the expression of Toll-like receptor 4 and myeloid differentiation factor 88 and blocked the phosphorylation of I kappa B kinase and nuclear factor-kappa *** results showed that rutin pretreatment may promote the phenotypic switch of microglia M1 to M2 by inhibiting the Toll-like receptor 4/nuclear factor-kappa B signaling pathway to alleviate lipopolysaccharide-induced neuroinflammation.

关键词： BV-2 cells flavonoid M1 microglia M2 microglia microglia activation microglia polarization neuroinflammation proinflammatory cytokines rutin TLR-4 signaling

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Mesenchymal stem cell-derived exosomes regulate microglia phenotypes:a promising treatment for acute central nervous system injury

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Neural Regeneration Research 2023年第8期18卷 1657-1665页

作者： Yu-Yan Liu Yun Li Lu Wang Yan Zhao Rui Yuan Meng-Meng Yang Ying Chen Hao Zhang Fei-Hu Zhou Zhi-Rong Qian Hong-Jun Kang Medical School of Chinese PLA BeijingChina Department of Critical Care Medicine the First Medical CenterChinese PLA General HospitalBeijingChina Beidou Precision Medicine Insititute GuangzhouGuangdong ProvinceChina

There is growing evidence that long-term central nervous system(CNS)inflammation exacerbates secondary deterioration of brain structures and functions and is one of the major determinants of disease outcome and *** acute CNS injury,brain microglia are among the first cells to respond and play a critical role in neural repair and ***,microglial activation can also impede CNS repair and amplify tissue damage,and phenotypic transformation may be responsible for this dual *** stem cell(MSC)-derived exosomes(Exos)are promising therapeutic agents for the treatment of acute CNS injuries due to their immunomodulatory and regenerative ***-Exos are nanoscale membrane vesicles that are actively released by cells and are used clinically as circulating biomarkers for disease diagnosis and ***-Exos can be neuroprotective in several acute CNS models,including for stroke and traumatic brain injury,showing great clinical *** review summarized the classification of acute CNS injury disorders and discussed the prominent role of microglial activation in acute CNS inflammation and the specific role of MSC-Exos in regulating pro-inflammatory microglia in neuroinflammatory repair following acute CNS ***,this review explored the potential mechanisms and factors associated with MSCExos in modulating the phenotypic balance of microglia,focusing on the interplay between CNS inflammation,the brain,and injury aspects,with an emphasis on potential strategies and therapeutic interventions for improving functional recovery from early CNS inflammation caused by acute CNS injury.

关键词： acute CNS injury central nervous system inflammation exosome immune regulation mesenchymal stem cell mesenchymal stem cell-derived exosomes(MSC-Exos) microglia activation microglia phenotypic transformation molecular mechanism neuroinflammation

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In depth understanding of retinitis pigmentosa pathogenesis through optical coherence tomography angiography analysis:a narrative review

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International Journal of Ophthalmology(English edition) 2021年第12期14卷 1979-1985页

作者： Bing-Wen Lu Guo-Jun Chao Gai-Ping Wu Li-Ke Xie Department of Ophthalmology Ophthalmology Hospital of China Academy of Traditional Chinese MedicineBeijing 100040China

Retinitis pigmentosa(RP)is the most recognized inherited retinal disorder involving progressive photoreceptors degeneration which eventually causes ***,the pathogenesis of RP is still unclear,making it difficult to establish satisfying *** have been found to support the theory that vascular dysfunction is associated with the progression of *** coherence tomography angiography(OCTA)is a newly developed technology that enables visualization as well as quantitative assessment of retinal and choroidal vasculature *** in OCTA have opened a window for indepth understanding of RP ***,we propose a hypothesis of RP pathogenesis based on the current OCTA findings in RP,which includes four stages and two important key factors,vascular dysfunction and microglia ***,we discuss the future animal experiments needed and how advanced OCTA technology can help to further verity the *** final goal is to explore potential treatment options with enhanced understanding of RP pathogenesis.

关键词： retinitis pigmentosa optical coherence tomography angiography vascular dysfunction microglia activation

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Protective Effect of an Anthocyanin on Alzheimer’s Disease

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Advances in Bioscience and Biotechnology 2023年第12期14卷 505-513页

作者： Alya Al-Furaydi Noorah Saleh Al-Sowayan Department of Biology College of Science Qassim University Buraydah Saudi Arabia

Alzheimer’s, characterized by β-amyloid accumulation and tau hyperphosphorylation, is linked to inflammation, oxidative stress, and microglial activation, suggesting potential protective strategies. Studies have shown that natural polyphenolic anthocyanin components found in berries, such as cyanidin, can inhibit amyloid filament formation and modulate Alzheimer’s disease are polyphenolic flavonoids, which are responsible for red, purple, and blue colors in various fruits, such as red cabbage and most berries. Here, we reviewed the protective effects of anthocyanins. It has anti-inflammatory and antioxidant properties, reduces NF-κB, and affects inflammatory signaling pathways. They also improve cognitive function, making them a potential protective strategy against AD.

关键词： Anthocyanins Oxidative Stress microglia activation NF-κB

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Substantial subpial cortical demyelination in progressive multiple sclerosis: have we underestimated the extent of cortical pathology?

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Neuroimmunology and Neuroinflammation 2020年第1期7卷 51-67页

作者： Lauren Griffiths Richard Reynolds Rhian Evans Ryan J.Bevan Mark I.Rees Djordje Gveric James W.Neal Owain W.Howell Institute of Life Sciences Swansea University Medical SchoolSwansea UniversitySwansea SA28PPUK Department of Brain Sciences Faculty of MedicineImperial College LondonLondon W53EHUK Faculty of Medicine and Health University of SydneySydneyNew South Wales NSW 2006Australia

Aim: Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease. Much of the complex symptomatology relates to pathology outside the classic white matter plaque, whereby lesions of the cortical grey matter, which are difficult to resolve by conventional clinical imaging, are in part predictive of outcome. We investigated the extent of grey matter pathology in whole coronal macrosections to reassess the contribution of cortical pathology to total demyelinating lesion area in progressive MS. Methods: Twenty-two cases of progressive MS were prepared as whole bi-hemispheric macrosections for histology, immunostaining and quantitative analysis of lesion number and relative area, leptomeningeal inflammation and microglial/macrophage activation. Results: Cortical grey matter demyelination was seen in all cases, which was more extensive than in white and deep grey matter (hippocampus, thalamus and basal ganglia) and accounted for 0.8%-60.2% of the entire measurable cortical ribbon. The pattern of cortical grey matter demyelination was predominantly subpial (mean 90.9%, range 60%-100%, of total cortical grey matter lesion area) and cases with the largest areas of subpial cortical lesions had more and larger deep grey matter lesions, greater numbers of activated microglia/macrophages, both in lesions as well as in normal cortical grey matter, together with elevated leptomeningeal inflammation and lymphoid-like ;structures. White matter lesion area was unchanged when compared with the progressive MS cases with little subpial cortical demyelination. Conclusion: Analysis of whole coronal macrosections reveals cortical demyelination is more extensive than reported by conventional histological methods. Cases of progressive MS with substantial subpial cortical demyelination that is independent of underlying white matter lesion area support the implications that these lesions may in-part arise through different pathogenetic mechanisms. Biomarkers and/or i

关键词： Leptomeninges B cell follicle microglia activation normal appearing grey matter

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