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Neural Regeneration Research 2023年第1期18卷 141-149页

作者： Xi-Lei Liu Dong-Dong Sun mu-Tian Zheng Xiao-Tian Li Han-Hong Niu Lan Zhang Zi-Wei Zhou Hong-Tao Rong Yi Wang Ji-Wei Wang Gui-Li Yang Xiao Liu Fang-Lian Chen Yuan Zhou Shu Zhang Jian-Ning Zhang Department of Neurosurgery Tianjin Medical University General HospitalTianjinChina Tianjin Neurological Institute Key Laboratory of Post-Neuroinjury Repair and Regeneration in Central Nervous SystemTianjinChina Graduate School Tianjin Medical UniversityTianjinChina Department of Neurosurgery Tianjin Huanhu HospitalTianjin Key Laboratory of Cerebral Vascular and Neurodegenerative DiseasesTianjin Neurosurgical InstituteTianjinChina Department of Radiotherapy Tianjin Medical University General HospitalTianjinChina Department of Geriatrics Tianjin Medical University General HospitalTianjinChina Institute of Tianjin Geriatrics Tianjin Medical University General HospitalTianjinChina

Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory *** studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact *** or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive *** blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days *** results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from m1 to m2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after ***,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell ***,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,morris water maze test,and lesion volume *** summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.

关键词： C-C chemokine receptor type 5(CCR5)antagonist high mobility group protein B1(HmGB1) maraviroc m1 microglia nuclear factor-κB pathway NACHT,LRR,and PYD domains-containing protein 3(NLRP3)inflammasome neuroinflammation neurological function neurotoxic reactive astrocytes traumatic brain injury

Necroptosis plays a crucial role in the exacerbation of retinal injury after blunt ocular trauma

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Neural Regeneration Research 2023年第4期18卷 922-928页

作者： Yu Huan Xiu-Quan Wu Tao Chen Ya-Nan Dou Bo Jia Xin He Dong-Yu Wei Zhou Fei Fei Fei Department of Neurosurgery Xijing HospitalAir Force Medical UniversityXi’anShaanxi ProvinceChina Center of Clinical Aerospace medicine Air Force Medical UniversityXi’anShaanxi ProvinceChina Department of Aviation medicine Xijing HospitalAir Force Medical UniversityXi’anShaanxi ProvinceChina Department of Ophthalmology Xijing HospitalAir Force Medical UniversityXi’anShaanxi ProvinceChina

Retinal injury after blunt ocular trauma may directly affect prognosis and lead to vision *** investigate the pathological changes and molecular mechanisms involved in retinal injury after blunt ocular trauma,we established a weight drop injury model of blunt ocular trauma in male Beagle ***-eosin staining,immunofluorescence staining,western blotting,and TUNEL assays were performed to investigate retinal injury within 14 days after blunt ocular *** with the control group,the thicknesses of the inner and outer nuclear layers,as well as the number of retinal ganglion cells,gradually decreased within 14 days after *** number of bipolar cells in the inner nuclear layer began to decrease 1 day after injury,while the numbers of cholinergic and amacrine cells in the inner nuclear layer did not decrease until 7 days after ***,retinal cell necroptosis increased with time after injury;it progressed from the ganglion cell layer to the outer nuclear *** electrophysiological findings indicated that visual impairment began on the first day after injury and worsened over ***,blunt ocular trauma induced nerve regeneration and müller glial hyperplasia;it also resulted in the recruitment of microglia to the retina and polarization of those microglia to the m1 *** findings suggest that necroptosis plays an important role in exacerbating retinal injury after blunt ocular trauma via gliosis and *** a role has important implications for the development of therapeutic strategies.

关键词： Beagle dogs blunt ocular trauma gliosis m1 microglia müller cells necroptosis neuroinflammation retinal ganglion cells retinal injury weight drop injury

Lycium barbarum extract promotes m2 polarization and reduces oligomeric amyloid-β-induced inflammatory reactions in microglial cells

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Neural Regeneration Research 2022年第1期17卷 203-209页

作者： Zhong-Qing Sun Jin-Feng Liu Wei Luo Ching-Hin Wong Kwok-Fai So Yong Hu Kin Chiu Department of Ophthalmology Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina State Key Laboratory of Brain and Cognitive Sciences The University of Hong KongHong Kong Special Administrative RegionChina Guangdong-Hong Kong-macao Institute of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina Department of Orthopaedics&Traumatology The University of Hong KongHong Kong Special Administrative RegionChina

Lycium barbarum(LB)is a traditional Chinese medicine that has been demonstrated to exhibit a wide variety of biological functions,such as antioxidation,neuroprotection,and immune *** of the main mechanisms of Alzheimer’s disease is that microglia activated by amyloid beta(Aβ)transform from the resting state to an m1 state and release pro-inflammatory cytokines to the surrounding *** the present study,immortalized microglial cells were pretreated with *** extract for 1 hour and then treated with oligomeric Aβfor 23 *** results showed that LB extract significantly increased the survival of oligomeric Aβ-induced microglial cells,downregulated the expression of m1 pro-inflammatory markers(inducible nitric oxide synthase,tumor necrosis factorα,interleukin-6,and interleukin-1β),and upregulated the expression of m2 anti-inflammatory markers(arginase-1,chitinase-like protein 3,and interleukin-4).LB extract also inhibited the oligomeric Aβ-induced secretion of tumor necrosis factorα,interleukin-6,and interleukin-1βin microglial *** results of in vitro cytological experiments suggest that,in microglial cells,LB extract can inhibit oligomeric Aβ-induced m1 polarization and concomitant inflammatory reactions,and promote m2 polarization.

关键词： Alzheimer’s disease amyloid-β anti-inflammatory factors Lycium barbarum extract m1 microglia m2 microglia neuroinflammation proinflammatory factors

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