Neuroimmunology and Neuroinflammation最新文献

{"title":"Resolution of inflammation and repair after ischemic brain injury","authors":"A. Yoshimura, Minako Ito","doi":"10.20517/2347-8659.2020.22","DOIUrl":"https://doi.org/10.20517/2347-8659.2020.22","url":null,"abstract":"After ischemic stroke, proinflammatory molecules known as danger-associated molecular patterns (DAMPs) originating from damaged brain cells recruit and activate immune cells (neutrophils, macrophages, lymphocytes) further eliciting innate and adaptive immunity. During the acute phase from day 1 to day 3 of the stroke onset, macrophages play a major role in the progression of inflammation, promoting the destruction of brain tissue. During the recovery phase, from day 3~4 to day 7 after stroke onset, infiltrating macrophages switch to repairing macrophages, which clear the DAMPs and promote tissue repair by producing neurotrophic factors. Adaptive immunity during the late or chronic phase (> day 7) of stroke has not been well investigated. Recent studies have also indicated that antigen-specific T cells, especially regulatory T cells (Tregs), play major roles in neural repair. This review focuses mainly on the resolution of inflammation and tissue repair by macrophages and Tregs.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43609033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The immune regulation of PD-1/PDL-1 axis, a potential biomarker in multiple sclerosis","authors":"M. T. Cencioni","doi":"10.20517/2347-8659.2020.18","DOIUrl":"https://doi.org/10.20517/2347-8659.2020.18","url":null,"abstract":"Multiple sclerosis is an autoimmune disease characterised by a chronic inflammation within the central nervous system. In the last ten years, studies on multiple sclerosis have been concentrated on the discovery of new biomarkers of disease and potential therapeutic targets. In chronic infection or in cancer, the immune system response is faulty and maintained in a condition defined as T-cell exhaustion induced by expression of co-inhibitory receptors. The PD-1/PDL-1 pathway is demonstrated to be the main one responsible for promoting T-cell exhaustion, and immunotherapies targeting PD-1 or PDL-1 have shown beneficial clinical outcomes in several tumours and chronic diseases. Contrarily, transcriptional T-cell exhaustion signature and high expression of co-inhibitor receptor PD-1 are associated with favourable prognosis in multiple sclerosis and other autoimmune diseases. Several studies have clearly demonstrated PD-1 has a dual role in immune self-tolerance: to constrain autoreactive T cells in anergic condition and to protect the tissue from the damage caused by the activation of endogenous autoreactive T cells. Consequently, immune checkpoint inhibitor therapies that target inhibitory receptors in cancer cause an exacerbation of autoimmune diseases. This review describes the roles of the PD-1/ PDL-1 pathway in cancer and autoimmune diseases, especially in multiple sclerosis, and how manipulating PD-1 can be a therapeutic approach in multiple sclerosis.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45343159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical efficacy and safety of single cycle rituximab as induction therapy for aggressive neuromyelitis optica spectrum disorder in a resource limited center: a preliminary study","authors":"T. Ong, S. Viswanathan, S. Ong, F. Hiew","doi":"10.20517/2347-8659.2020.05","DOIUrl":"https://doi.org/10.20517/2347-8659.2020.05","url":null,"abstract":"Aim: To analyse the efficacy of single dose rituximab (RTX) as induction therapy followed by conventional oral steroid-sparing agents (azathioprine, mycophenolate mofetil or methotrexate) in a cohort of patients with aggressive neuromyelitis optica spectrum disorder (NMOSD) without CD19, 20 and 27 biomarker testing. Methods: A retrospective analysis of clinical outcomes in eight patients with aggressive NMOSD treated with one course of RTX induction therapy in the Neurology Department at Kuala Lumpur Hospital from 2005 to 2018 was performed. The effectiveness of the treatment was determined by the number of relapses, expanded disability status scale, annualized relapsed rates, and modified Rankin Scale both before and after treatment. B cell enumeration testing was done instead of CD19, 20 and 27 biomarker testing. Results: There was a reduction in the mean annualized relapse rate from 4.7 to 0.5 attacks per year after treatment (P = 0.011). Mean expanded disability status scale and modified Rankin Scale values improved from 5.4 to 3.6 (P = 0.018) and 3.6 to 2.6 (P = 0.023), respectively. No patient developed any adverse effect. Conclusion: Single-course RTX induction therapy regime may be an alternative therapeutic option in resource limited hospitals to suppress NMOSD disease activity in the short term as pulse induction therapy whilst awaiting the effectiveness of conventional steroid-sparing agents. Further prospectively designed studies are required to prove efficacy. Original Article Page 312 Ong et al. Neuroimmunol Neuroinflammation 2020;7:311-8 I http://dx.doi.org/10.20517/2347-8659.2020.05","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43806029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining activation states of microglia in human brain tissue: an unresolved issue for Alzheimer’s disease","authors":"D. Walker","doi":"10.20517/2347-8659.2020.09","DOIUrl":"https://doi.org/10.20517/2347-8659.2020.09","url":null,"abstract":"The development of concepts concerning the role of microglia in different brain diseases has relied on studies of animal models or human brain tissue, which primarily use antibodies and immunohistochemistry techniques to make observations. Since initial studies defined increased expression of the major histocompatibility complex II protein human leukocyte antigen-DR as a means of identifying reactive, and therefore by implication, damagecausing microglia in Alzheimer’s disease (AD) or Parkinson’s disease (PD), understanding and describing their activation states has evolved to an unexpected complexity. It is still difficult to ascertain the specific functions of individual microglia, particularly those associated with pathological structures, using a narrow range of antigenic markers. As many approaches to developing treatments for AD or PD are focused on anti-inflammatory strategies, a more refined understanding of microglial function is needed. In recent years, gene expression studies of human and rodent microglia have attempted to add clarity to the issue by sub-classification of messenger RNA expression of cell-sorted microglia to identify disease-associated profiles from homeostatic functions. Ultimately all newly identified markers will need to be studied in situ in human brain tissue. This review will consider the gaps in knowledge between using traditional immunohistochemistry approaches with small groups of markers that can be defined with antibodies, and the findings from cell-sorted and single-cell RNA sequencing transcription profiles. There have been three approaches to studying microglia in tissue samples: using antigenic markers identified from studies of peripheral macrophages, studying proteins associated with altered genetic risk factors for disease, and studying microglial proteins identified from mRNA expression analyses from cell-sorting and gene profiling. The technical aspects of studying microglia in human brain samples, inherent issues of working with antibodies, and findings of a range of different functional microglial markers will be reviewed. In particular, we will consider Review Walker. Neuroimmunol Neuroinflammation 2020;7:194-214 I http://dx.doi.org/10.20517/2347-8659.2020.09 Page 195 markers of microglia with expression profiles that do not definitively fall into the pro-inflammatory or antiinflammatory classification. These additional markers include triggering receptor expressed on myeloid cells-2, CD33 and progranulin, identified from genetic findings, colony stimulating factor-1 receptor, purinergic receptor P2RY12, CD68 and Toll-like receptors. Further directions will be considered for addressing crucial issues.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43968125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarker-based diagnosis of cognitive disorders in a case series","authors":"E. Kapaki, V. Constantinides, Efstratios-Stylianos Pyrgelis, P. Paraskevas, J. Papatriantafyllou, G. Paraskevas","doi":"10.20517/2347-8659.2019.26","DOIUrl":"https://doi.org/10.20517/2347-8659.2019.26","url":null,"abstract":"The classical cerebrospinal fluid biomarkers of Alzheimer’s Disease (namely total tau, phospho-tau and amyloid beta peptide) have received much attention, since they can detect the biochemical fingerprint of Alzheimer’s disease and serve as a diagnostic aid for correct diagnosis of cognitive disorders during life. In this case series, we present 6 examples of patients with cognitive impairment of various types and severities and how biomarker data were helpful in every day diagnostic approach, combined with clinical, neuropsychological and imaging data and based on the most recent guidelines and recommendations.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46440611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglial heterogeneity: distinct cell types or differential functional adaptation?","authors":"S. Benusa, N. M. George, J. Dupree","doi":"10.20517/2347-8659.2020.03","DOIUrl":"https://doi.org/10.20517/2347-8659.2020.03","url":null,"abstract":"Microglia were first characterized by del Rio Hortega about 100 years ago but our understanding of these cells has only gained traction in the last 20 years. We now recognize that microglia are involved in a plethora of activities including circuitry refinement, neuronal and glial trophic support, cell number modulation, angiogenesis and immune surveillance. Specific to immune surveillance, microglia detect threats which then drive their transformation from ramified to amoeboid cells. This morphological transition is accompanied by changes in cytokine and chemokine expression, which are far less conserved than morphology. To simplify discussion of these expression changes, nomenclature ascribed to states of macrophage activation, known as Macrophage 1 (“M1”; classic) and Macrophage 2 (“M2”; alternative), have been assigned to microglia. However, such a classification for microglia is an oversimplification that fails to accurately represent the array of cellular phenotypes. Additionally, multiple subclasses of microglia have now been described that do not belong to the “M1/M2” classification. Here, we provide a brief review outlining the prominent subclasses of microglia that have been described recently. Additionally, we present novel NanoString data demonstrating distinct microglial phenotypes from three commonly used central nervous system inflammation murine models to study microglial response and conclude with an introduction of recent RNA sequencing studies. In turn, this may not only facilitate a more appropriate naming scheme for these enigmatic cells, but more importantly, provide a framework for generating microglial expression “fingerprints” that may assist in the development of novel therapies by targeting disease-specific microglial subtypes.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41888999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebrospinal fluid biomarkers for cognitive disorders. An introductory overview","authors":"G. Paraskevas","doi":"10.20517/2347-8659.2019.008","DOIUrl":"https://doi.org/10.20517/2347-8659.2019.008","url":null,"abstract":"The core (established) cerebrospinal fluid biomarkers of Alzheimer’s disease (AD), namely amyloid-beta peptide, total tau protein and phospho-tau protein, have become a part of the diagnostic workup of patients with cognitive disorders in many specialized centers, especially for ambiguous cases. Combined, these biomarkers can identify the presence or absence of an AD biochemical process with sensitivities and specificities approaching or exceeding 90% in both dementia and pre-dementia stages of AD. Thus, they have been incorporated in various sets of research or clinical diagnostic criteria and recommendations. Results that are atypical, incompatible with AD, or inconclusive may occur, necessitating the use of other cerebrospinal fluid or imaging biomarkers.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46162208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiome meets microglia in neuroinflammation and neurological disorders","authors":"Rachel E. Reyes, Zeyu Zhang, Lei Gao, L. Asatryan","doi":"10.20517/2347-8659.2020.13","DOIUrl":"https://doi.org/10.20517/2347-8659.2020.13","url":null,"abstract":"One of the emerging hot topics in biosciences is the intriguing link between gut microbial communities and its influences outside the gastrointestinal tract, such as the central nervous system (CNS), including its cognitive activities and immune responses. Beyond its neuroprotective properties, microglia are also critical for neuronal synaptic pruning and neural remodeling during CNS development. Prolonged microglia activation and neuroinflammation are considered key contributors to neurological disorders. In this regard, it is becoming increasingly important to consider the potential influences underlying the crosstalk between the intestinal microbiota ecosystem and host when determining biomarkers of disease and treatment efficacy. The commensal microbiota is critical for immune development and continuous function through the recognition of bacteriaproduced and regulated metabolites. In cases of microbial dysbiosis and microglial dysfunction, chronic neuroinflammation may persist, leading to the propagation of neurological disorders. To address potential mechanisms, this review focuses on the microbiota-gut-brain axis as it relates to communication pathways that have been linked to aberrant CNS immune activity and pathology. We also address anti-inflammatory and neuroprotective mediators which may counteract these detrimental activities. Finally, we explore the potential benefits of current and novel microbiome-targeted approaches to treat neuroinflammation and consequential neurological disease.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43686727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-CASPR2 antibodies clinical significance and its main phenotypes","authors":"Letícia Caroline Breis, M. Schlindwein, M. Gonçalves","doi":"10.20517/2347-8659.2020.14","DOIUrl":"https://doi.org/10.20517/2347-8659.2020.14","url":null,"abstract":"","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47750998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19 neurotropism and implications for therapy","authors":"M. Das, C. Penn, T. Martinez, Karthick Mayilsamy, Andrew R. McGill, Alison Wiling, S. Mohapatra, S. Mohapatra","doi":"10.20517/2347-8659.2020.36","DOIUrl":"https://doi.org/10.20517/2347-8659.2020.36","url":null,"abstract":"The mechanism underlying the pathogenesis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in humans is poorly understood, although the cellular receptors which facilitate the virus fusion have been identified. Although the major symptoms of the infection have been identified as acute respiratory distress, pneumonia, and fever, recently, symptoms involving nervous system dysfunctions, including encephalopathy and stroke, have been detected. Herein, we comprehensively review the evidence that SARS-CoV-2 infection involves a neurotropic mechanism including a nose-brain-lung axis suggesting implications in therapy development.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42417981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}