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Neuroinf lammation

Neuroscience Bulletin 2015年第6期31卷 714-716页

作者： fu-dong shi Department of Neurology Tianjin Neurological InstituteTianjin Medical University General Hospital Department of Neurology Barrow Neurological InstituteSt.Joseph's Hospital and Medical Center

The central nervous system （CNS）, i.e. brain and spinal cord, is conventionally perceived as an immunologically- privileged site in that the tight junctions of endothelial cells, namely the blood brain barrier （BBB）, shields the CNS from invasion by lymphocytes from the circulation. However, the integrity of the BBB is compromised in a number of pathological conditions such as traumatic brain injury, multiple sclerosis （MS）, and stroke, which results in the infiltration of an array of lymphocytes from the periphery. Brain intrinsic microglia and astrocytes are highly proactive in interactions with the migrant lymphocytes. These interactions often lead to the release of inflammatory cytokines, in situ cell proliferation, and immune-mediated damage of myelin sheaths and secondary damage to axons and neurons in the case of MS. MS is an example of a group of classic neuroinflammatory diseases, in that inflammation and immune responses are the primary causes of CNS pathology. In this group of disorders, immune responses within the brain evolve in terms of intensity and antigen specificity. Such evolution often takes many years before causing overt pathology. In contrast, immune invasion and inflammation occur minutes to hours after traumatic brain injury, acute intracerebral hemorrhage （ICH）, or acute ischemic stroke （AIS）.

关键词： ICH AIS

Dissemination of brain inflammation in traumatic brain injury

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Cellular & Molecular Immunology 2019年第6期16卷 523-530页

作者： Kaibin shi Jianning Zhang Jing-fei dong fu-dong shi Departments of Neurology and Neurosurgery Tianjin Neurological InstituteTianjin Medical University General HospitalTianjin 300052China Center for Neuroinflammation Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China Department of Neurology Barrow Neurological InstituteSt.Joseph’s Hospital and Medical CenterPhoenixAZ 85013USA BloodWorks Northwest Research Institute Division of HematologyDepartment of MedicineSchool of MedicineUniversity of WashingtonSeattleWA 98195USA

Traumatic brain injury(TBI)is recognized as a global health problem due to its increasing occurrence,challenging treatment,and persistent impacts on brain *** cell death in patients with TBI swiftly causes inflammation in the injured brain areas,which is recognized as focal brain *** brain inflammation causes secondary brain injury by exacerbating brain edema and neuronal death,while also exerting divergent beneficial effects,such as sealing the damaged limitans and removing cellular *** evidence from patients with TBI and studies on animal models suggest that brain inflammation after TBI is not only restricted to the focal lesion but also disseminates to remote areas of the *** dissemination of inflammation has been detected within days after the primary injury and persists *** state of inflammation may be related to remote complications of TBI in patients,such as hyperthermia and hypopituitarism,and may lead to progressive neurodegeneration,such as chronic traumatic *** studies should focus on understanding the mechanisms that govern the initiation and propagation of brain inflammation after TBI and its impacts on post-trauma brain pathology.

关键词： disseminated brain inflammation traumatic brain injury microglia post-injury neurodegeneration

Stroke-induced immunosuppression and poststroke infection

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Stroke & Vascular Neurology 2018年第1期3卷 34-41页

作者： Kaibin shi Kristofer Wood fu-dong shi Xiaoying Wang Qiang Liu Departments of Neurology Tianjin Neurological InstituteTianjin Medical University General HospitalTianjinChina Departments of Neurology Barrow Neurological InstituteSt.Joseph’s Hospital and Medical CenterPhoenixArizonaUSA Departments of Neurology and Radiology Neuroprotection Research LaboratoryMassachusetts General HospitalNeuroscience ProgramHarvard Medical SchoolBostonMassachusettsUSA

Infections occur commonly after stroke and are strongly associated with an unfavourable functional outcome of these *** for effective management of poststroke infection remain scarce,presenting an urgent need for preventive anti-infection strategies for patients who have suffered a *** evidence indicates that stroke impairs systemic immune responses and increases the susceptibility to infections,suggesting that the modification of impaired immune defence could be *** this review,we summarised previous attempts to prevent poststroke infections using prophylactic antibiotics and the current understanding of stroke-induced *** elucidation of the immune mechanisms of stroke will pave the way to tailored design of new treatment to combat poststroke infection via modifying the immune system.

关键词： infection impaired stroke

Clinical significance of detection of antibodies to fetal and adult acetylcholine receptors in myasthenia gravis

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Neuroscience Bulletin 2012年第5期28卷 469-474页

作者： Qi-Guang shi Zhi-Hong Wang Xiao-Wei Ma Da-Qi Zhang Chun-Sheng Yang fu-dong shi Li Yang Department of Neurology and Tianjin Neurological Institute Tianjin Medical University General Hospital Tianjin 300052 China Department of Neurology Barrow Neurological Institute St. Joseph's Hospital and Medical Center Phoenix Arizona 85013 USA

Objective To evaluate the frequency, distribution and clinical significance of the antibodies to the fetal and/or adult acetylcholine receptor （AChR） in patients with myasthenia gravis （MG）. Methods AChR antibodies were detected by cell-based assay in the serum of ocular MG （OMG）（n = 90） and generalized MG （GMG） patients （n = 110）. The fetal-type （2α： β： γ： δ） and adult-type （2α： β： ε： δ） AChR were used as antigens, and their relevance to disease presentation was assessed. Results The overall frequencies of anti-adult and anti-fetal AChR antibodies were similar in all 200 patients examined, with 14 having serum specific to the AChR-γ subunit, and 22 to the AChR-ε subunit. The overall sensitivity when using the fetal and adult AChR antibodies was higher than that when using the fetal AChR antibody only （P = 0.015）. Compared with OMG patients, the mean age at disease onset and the positive ratio of antibodies to both isoforms of the AChR were significantly higher in patients who subsequently progressed to GMG. Older patients and patients with both anti-fetal and anti-adult AChR antibodies had a greater risk for developing generalized disease [odds ratio （OR）, 1.03; 95% confidence interval （CI）, 1.01–1.06 and OR, 5.09; 95% CI, 2.23–11.62]. Conclusion Using both fetal-and adult-type AChRs as the antigens may be more sensitive than using either subtype. Patients with serum specific to both isoforms are at a greater risk of progressing to GMG. Patients with disease onset at an advanced age appear to have a higher frequency of GMG conversion.

关键词： myasthenia gravis acetylcholine receptor antibodies acetylcholine receptor subunit cell-based assay adult fetal

Fingolimod alters inflammatory mediators and vascular permeability in intracerebral hemorrhage

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Neuroscience Bulletin 2015年第6期31卷 755-762页

作者： Yu-Jing Li Guo-Qiang Chang Yuanchu Liu Ye Gong Chunsheng Yang Kristofer Wood fu-dong shi Ying fu Yaping Yan Department of Neurology Tianjin Neurological InstituteTianjin Medical University General Hospital Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest ChinaCollege of Life SciencesShaanxi Normal University Department of Neurology Barrow Neurological InstituteSt. Joseph's Hospital and Medical Center

Intracerebral hemorrhage （ICH） leads to high rates of death and disability. The pronounced inflammatory reactions that rapidly follow ICH contribute to disease progression. Our recent clinical trial demonstrated that oral administration of an immune modulator fingolimod restrained secondary injury derived from initial hematoma, but the mechanisms remain unknown. In this study, we aim to investigate the effects of fingolimod on inflammatory mediators and vascular permeability in the clinical trial of oral fingolimod for intracerebral hemorrhage （ICH）. The results showed that fingolimod decreased the numbers of circulating CD4~ T, CD8~ T, CD19~ B, NK, and NKT cells and they recovered quickly after the drug＇ was stopped. The plasma ICAM level was decreased and IL-10 was increased by fingolimod. Interestingly, fingolimod protected vascular permeability as indicated by a decreased plasma level of MMP9 and the reduced rT1%. In conclusion, modulation of systemic inflammation by fingolimod demonstrates that it is an effective therapeutic agent for ICH. Fingolimod may prevent perihematomal edema enlargement by protecting vascular permeability.

关键词： fingolimod inflammatory mediator vascular permeability intracerebral hemorrhage

Alterations of natural killer cells in traumatic brain injury

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Neuroscience Bulletin 2014年第6期30卷 903-912页

作者： Xiao-dong Kong Sheng Bai Xin Chen Hui-Jie Wei Wei-Na Jin Min-Shu Li Yaping Yan fu-dong shi Departments of Neurology and Neurosurgery Key Laboratory of Post-trauma Neuro-repair and Regeneration in the Central Nervous SystemMinistry of EducationTianjin Neurological InstituteTianjin Medical University General Hospital Department of Geriatrics Tianjin Geriatrics InstituteTianjin Medical University General Hospital Department of Neurology Barrow Neurological InstituteSt.Joseph's Hospital and Medical CenterPhoenixAZUSA

To investigate the relationship between natural killer（NK） cells and traumatic brain injury（TBI）, we tracked an established phenotype of circulating NK cells at several time points in patients with different grades of TBI. In serial peripheral blood samples, NK cells were prospectively measured by flow cytometry of CD3-CD56＋ lymphocytes. Compared to healthy controls, TBI patients had reductions in both the percentage and the absolute number of NK cells. furthermore, the magnitude of NK cell reduction correlated with the degree of TBI severity at several time points. That is, NK cell population size was independently associated with lower Glasgow Coma Scale scores. In addition, at some time points, a positive correlation was found between the NK cell counts and Glasgow Outcome Scale scores. Our results indicate that TBI induces a reduction in the number of NK cells, and the magnitude of the reduction appears to parallel the severity of TBI.

关键词： natural killer cells traumatic brain injury central nervous system immunity

Autoantibody to MOG suggests two distinct clinical subtypes of NMOSD

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Science China(Life Sciences) 2016年第12期59卷 1270-1281页

作者： Yaping Yan Yujing Li Ying fu Li Yang Lei Su Kaibin shi Minshu Li Qiang Liu Aimee Borazanci Yaou Liu Yong He Jeffrey L Bennett Timothy L Vollmer fu-dong shi Departments of Neurology and Immunology Tianjin Neurological Institute Tianjin Medical University General Hospital Tianjin 300052 China Department of Neurology Barrow Neurological Institute St. Joseph's Hospital and Medical Center Phoenix 85013 USA State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research Beijing Normal University Beijing 100875 China Department of Neurology University of Colorado School of Medicine Aurora 80045 USA

We characterized a unique group of patients with neuromyelitis optica spectrum disorder （NMOSD） who carded autoantibod- ies of aquaporin-4 （AQP4） and myelin-oligodendrocyte glycoprotein （MOG）. Among the 125 NMOSD patients, 10 （8.0%） were AQP4- and MOG-ab double positive, and 14 （11.2%） were MOG-ab single positive. The double-positive patients had a multiphase disease course with a high annual relapse rate （P=0.0431）, and severe residual disability （P〈0.0001）. Of the dou- ble-positive patients, 70% had MS-like brain lesions, more severe edematous, multifocal regions on spinal magnetic resonance imaging （MRI）, pronounced decreases of retinal nerve fiber layer thickness and atrophy of optic nerves. In contrast, patients with only MOG-ab had a higher ratio of monophasic disease course and mild residual disability. Spinal cord MRI illustrated multifocal cord lesions with mild edema, and brain MRIs showed more lesions around lateral ventricles. NMOSD patients carrying both autoantibodies to AQP4 and MOG existed and exhibited combined features of prototypic NMO and relaps- ing-remitting form of MS, whereas NMOSD with antibodies to MOG only exhibited an ＂intermediate＂ phenotype between NMOSD and MS. Our study suggests that antibodies against MOG might be pathogenic in NMOSD patients and that determi- nation of anti-MOG antibodies maybe instructive for management of NMOSD patients.

关键词： MOG antibody AQP4 antibody neuromyelitis optica spectrum disorder phenotype

Visualizing Seizure Propagation in Freely-moving Mice via Miniature Two-photon Microscopy

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Neuroscience Bulletin 2022年第12期38卷 1593-1597页

作者： Zhuoran Zhang shihe Jiang Kaibin shi Yan Li Wei‑Na Jin Qiang Liu Ting Zhao Heping Cheng fu‑dong shi Department of Neurology Tianjin Medical University General HospitalTianjin 300052China Center for Neurological Diseases China National Clinical Research Center for Neurological DiseasesBeijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Nanjing Brain Observatory PKU-Nanjing Institute of Translational MedicineNanjing 211899China State Key Laboratory of Membrane Biology Institute of Molecular MedicinePeking-Tsinghua Center for Life SciencesCollege of Future TechnologyPeking UniversityBeijing 100091China

DearEditor,Due to the tight and precise associations between behaviors and neural activities,the investigation of neuronal activity in freely-movingand behavinganimals isamajor unaccomplished goal in *** seizures,characterized by hyper-synchronized discharges and hyper-excitation in neuronal networks,are one of the most common neurological disorders.

关键词： moving precise excitation

Incidence and Mortality of Acute Disseminated Encephalomyelitis in China: A Nationwide Population-based Study

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Neuroscience Bulletin 2021年第6期37卷 804-808页

作者： Yuwen Xiu Hongqiu Gu Xindi Li Zixiao Li Wei-Na Jin Qiang Liu fu-dong shi China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Department of Neurology Tianjin Neurological InstituteTianjin Medical University General HospitalTianjin 300052China

Dear Editor,Acute disseminated encephalomyelitis(ADEM)is an immune-mediated demyelinating disorder characterized by a widespread attack of inflammation in the brain and spinal cord that damages myelin[1].ADEM is life-... 详细信息

关键词： Acute inflammation myelitis