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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

Consensus for prevention and management of coronavirus disease 2019 (COVID-19) for neurologists

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Stroke & Vascular Neurology 2020年第2期5卷 146-151页

作者： Huijuan Jin Candong Hong Shengcai Chen Yifan Zhou Yong Wang Ling Mao Yanan Li Quanwei He Man Li Ying Su David Wang Longde Wang Bo Hu Department of Neurology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina Neurovascular Division Department of NeurologyBarrow Neurological Institute/Saint Joseph Hospital Medical CenterPhoenixAZUSA Stroke Prevention and Control Steering Committee National Health Commission of the People’s Republic of ChinaBeijingChina

Coronavirus disease 2019(COVID‐19)has become a pandemic disease *** COVID-19 directly invades lungs,it also involves the nervous ***,patients with nervous system involvement as the presenting symptoms in the early stage of infection may easily be misdiagnosed and their treatment *** become silent contagious sources or‘virus spreaders’.In order to help neurologists to better understand the occurrence,development and prognosis,we have developed this consensus of prevention and management of COVID‐*** can also assist other healthcare providers to be familiar with and recognise COVID-19 in their evaluation of patients in the clinic and hospital environment.

关键词： prevention involvement prognosis

S2A-3 The Alpha6*-nAChR is A Highly Sensitive Target for Low Dose Alcohol

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神经药理学报 2018年第4期8卷 36-37页

作者： WU Jie Division of Neurology Barrow Neurological InstituteSt.Joseph’s Hospital and Medical CenterPhoenix AZ 85013USA

Alcohol use disorder(AUD)is a serious public health problem that affects approximately 17 million Americans and results in tremendous social,legal and medical costs to the *** other addictive drugs(e.g.,morphine,cocaine or nicotine)that have specific molecular targets,ethanol(EtOH)has no specific *** most previous studies,EtOH concentrations used for investigation were too high(e.g.,>50 mmol·L-1)compared to the EtOH concentrations in human brain after alcohol drinking,and the high dose EtOH may produce nonspecific modulations of a variety of receptors,ion channels,intracellular signaling cascades,and gene expression in the ***,it is important to understand low dose(e.g.,<10 mmol·L-1)EtOH effects in the ***,the molecular and cellular targets that mediate the sensitivity to low dose EtOH remain to be *** containingα6 subunits(α6*-nAChRs)shows a highly restricted distribution in midbrain dopaminergic neurons that are associated with drug dependence and ***,we report that low dose EtOH(0.1~5 mmol·L-1)significantly potentiatesα6*-nAChR function using patch-clamp whole-cell *** EtOH modulatesα6*-nAChR-mediated function depending on both EtOH and nicotine concentrations,representing a positive allosteric *** conclusion,our results demonstrate a functionalα6*-nAChR transfected in human SH-EP1 cells that can be used as an excellent cell model to investigateα6*-nAChR function and *** patch-clamp recording condition,low dose EtOH modulatesα6*-nAChR function as a positive allosteric *** this mechanism,brainα6*-nAChRs may play a critical role in mediating low dose alcohol’effects on alcohol reward and dependence.

关键词： EtOH mediate the sensitivity

Diversity of functional nicotinic acetylcholine receptor subtypes in rat VTA dopaminergic neurons and nicotine dependence

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Diversity of functional nicotinic acetylcholine receptor sub...

Stroke-induced immunosuppression and poststroke infection

第十五届国际药理学大会

作者： Lucero Linda Lukas Ronald Division of Neurobiology Barrow Neurological Institute 350 W.Thomas Rd Phoenix AZ 85013 USA. Division of Neurobiology Barrow Neurological Institute 350 W.Thomas Rd Phoenix AZ 85013 USA.

＜正＞ Dopaminergic （ DA） neurons located in the midbrain ventral tegmental area （VTA） play important roles in nicotine reward and dependence. Nicotinic acetyl choline receptor （nAChR） a2 - a7 and b2 - b4 subunits are expressed as message in the VTA. but the functions of nAChR subtypes are unclear. Using patch clamp recording from single DA neurons acutely dissociated from the VTA. we have discriminated three types of nAChR - mediated responses based on pharmacological and kinetic properties. Type Ⅰ neurons （58%） responded strongly to RJR - 2403. which was blocked by dihydro - b - erythroidine, suggesting a a4b2 -nAChR. Type n neurons （26%） reacted strongly to choline. which was blocked by 10 nM methyllycaconitine, suggesting a a7 - nAChR. However, type Ⅲ neurons （16% ） exhibited large, slowly - decaying current responses to both ACh and cytisine, suggesting a possibly complex mixture of nAChR subtypes （a3a4b2b4）. During 10 - min exposure to 500 nM nicotine, only type Ⅰ neuron firing was persistently increased. Conclusion: VTA DA neurons express three subtypes of nAChR which play different roles in nicotine reward and dependence.

关键词： nAChR VTA DA neuron patch-clamp.

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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

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

Mechanisms of Cannabinoid CB2 ReceptorMediated Modulations in Mouse VTA Dopamine Neurons

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神经药理学报 2019年第Z1期 68-69页

作者： WU Jie barrow Neurological Institute St.Joseph’s Hospital and Medical Center Brain Function and Disease Institute Qingdao University Shantou University Medical College

Objective:Growing evidence suggests that brain cannabinoid CB2 receptors（CB;Rs） are importantly involved in several dopamine（DA）-related behaviors and DA-related CNS disorders. We recently reported that brain CB;Rs modulate cocaine’s action,including intravenous cocaine self-administration,cocaine-enhanced locomotion and extracellular DA in the nucleus accumbens in mice. In addition,CB;Rs are recently identified in mouse VTA DA neurons,and activation of CB;Rs in the VTA reduces DA neuron excitability and firing rates in both in vitro and in vivo preparations. However,the cellular and molecular mechanisms underlying the CB;R-mediated reduction in VTA DA neuronal excitability are unknown. Methods:In the present study,we addressed this issue by using patch-clamp recordings in two preparations:the VTA slices and the freshly-dissociated single VTA neurons. Molecular and cell-biological approaches were used to identify the expression of CB2 receptors in the VTA neurons. Results:To elucidate the synaptic mechanism,we recorded spontaneous excitatory or inhibitory presynaptic currents（EPSCs,IPSCs） in VTA DA neurons in midbrain slides. We found that bath-applied JWH133（a selective CB;R agonist） slightly reduced the frequency of sEPSCs but not sIPSCs,suggesting that the activation of CB;Rs can mildly reduce presynaptic glutamate release probability. However,pharmacological block of glutamatergic synaptic transmission failed to prevent the CB;Rmediated inhibition of VTA DA neuronal firing. Then,we used perforated patch-clamp recordings in acutely-dissociated single VTA DA neurons to study the effects of JWH133 on the intrinsic membrane properties of VTA DA neurons. We found that bath-applied JWH133 produced an enhancement of M-type K+ channel currents. This effect is mediated by activation of CB;Rs in VTA DA neurons because co-administration of AM630,a selective CB;R antagonist,or genetic deletion of CB;Rs（using CB;R knockout mice） eliminated the JWH133-induced potentiation on

关键词： cannabinoid receptor 2 VTA DA neurons neuronal excitability patch-clamp

Surgical Anatomy & Techniques to the Spine

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Automatic counting of microglial cell activation and its applications

2006年

作者： Daniel H. Kim Alexander R. Vaccaro Jeffrey S. Henn Curtis A. Dickman

ISBN: (纸本)9781416003137

Written by three neurosurgeons and an orthopedic surgeon, this comprehensive reference's multidisciplinary approach makes it relevant and informative to all surgeons regardless of their specialty or level of surgical experience. After thoroughly reviewing the anatomy and approaches to the spine, the authors lead you through a full range of state-of-the-art techniques in spine surgery, including those procedures commonly performed for degenerative disease, trauma, scoliosis, tumor, and infection. Abundant full-color illustrations, three-dimensional images and cadaver dissection photos walk you through both simple and complex spinal surgical procedures. The bonus CD-ROM contains all the images from the book, including some of the most sought-after anatomic photographs and radiographic images in neurosurgery, brought together for the first time uniquely for this volume.

关键词： Spinesurgery.

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Neural Regeneration Research 2016年第8期11卷 1212-1215页

作者： Beatriz I.Gallego Collado Pablo de Gracia Instituto de Investigaciones Oftalmologicas Ramon Castroviejo Universidad Complutense de Madrid Madrid Spain Facultad de Optica y Optometria Departamento de Oftalmologia y Otorrinolaringologia Universidad Complutense de Madrid Madrid Spain Midwestern University Chicago College of Optometry Downers Grove IL USA Department of Neurobiology Barrow Neurological Institute St. Joseph's Hospital and Medical Center Phoenix AZ USA

Glaucoma is a multifactorial optic neuropathy characterized by the damage and death of the retinal ganglion *** disease results in vision loss and *** vision loss resulting from the disease cannot be restored and nowadays there is no available cure for glaucoma; however an early detection and treatment,could offer neuronal protection and avoid later serious damages to the visual function.A full understanding of the etiology of the disease will still require the contribution of many scientific *** activation has been observed in glaucoma,being microglial proliferation a hallmark in this neurodegenerative disease.A typical project studying these cellular changes involved in glaucoma often needs thousands of images- from several animals- covering different layers and regions of the *** gold standard to evaluate them is the manual *** method requires a large amount of time from specialized *** is a tedious process and prone to human *** present here a new method to count microglial cells by using a computer *** counts in one hour the same number of images that a researcher counts in four weeks,with no loss of reliability.

关键词： glaucoma glial cells microglial cells automatic counting image processing inner plexiform layer outer plexiform layer bilateral activation