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      Neuroinflammation and Infection: Molecular Mechanisms Associated with Dysfunction of Neurovascular Unit

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          Abstract

          Neuroinflammation is a complex inflammatory process in the central nervous system, which is sought to play an important defensive role against various pathogens, toxins or factors that induce neurodegeneration. The onset of neurodegenerative diseases and various microbial infections are counted as stimuli that can challenge the host immune system and trigger the development of neuroinflammation. The homeostatic nature of neuroinflammation is essential to maintain the neuroplasticity. Neuroinflammation is regulated by the activity of neuronal, glial, and endothelial cells within the neurovascular unit, which serves as a “platform” for the coordinated action of pro- and anti-inflammatory mechanisms. Production of inflammatory mediators (cytokines, chemokines, reactive oxygen species) by brain resident cells or cells migrating from the peripheral blood, results in the impairment of blood-brain barrier integrity, thereby further affecting the course of local inflammation. In this review, we analyzed the most recent data on the central nervous system inflammation and focused on major mechanisms of neurovascular unit dysfunction caused by neuroinflammation and infections.

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          Most cited references137

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          Origin and physiological roles of inflammation.

          Inflammation underlies a wide variety of physiological and pathological processes. Although the pathological aspects of many types of inflammation are well appreciated, their physiological functions are mostly unknown. The classic instigators of inflammation - infection and tissue injury - are at one end of a large range of adverse conditions that induce inflammation, and they trigger the recruitment of leukocytes and plasma proteins to the affected tissue site. Tissue stress or malfunction similarly induces an adaptive response, which is referred to here as para-inflammation. This response relies mainly on tissue-resident macrophages and is intermediate between the basal homeostatic state and a classic inflammatory response. Para-inflammation is probably responsible for the chronic inflammatory conditions that are associated with modern human diseases.
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            The role of inflammation in depression: from evolutionary imperative to modern treatment target.

            Crosstalk between inflammatory pathways and neurocircuits in the brain can lead to behavioural responses, such as avoidance and alarm, that are likely to have provided early humans with an evolutionary advantage in their interactions with pathogens and predators. However, in modern times, such interactions between inflammation and the brain appear to drive the development of depression and may contribute to non-responsiveness to current antidepressant therapies. Recent data have elucidated the mechanisms by which the innate and adaptive immune systems interact with neurotransmitters and neurocircuits to influence the risk for depression. Here, we detail our current understanding of these pathways and discuss the therapeutic potential of targeting the immune system to treat depression.
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              Local self-renewal can sustain CNS microglia maintenance and function throughout adult life.

              Microgliosis is a common response to multiple types of damage in the CNS. However, the origin of the cells involved in this process is still controversial and the relative importance of local expansion versus recruitment of microglia progenitors from the bloodstream is unclear. Here, we investigated the origin of microglia using chimeric animals obtained by parabiosis. We found no evidence of microglia progenitor recruitment from the circulation in denervation or CNS neurodegenerative disease, suggesting that maintenance and local expansion of microglia are solely dependent on the self-renewal of CNS resident cells in these models.
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                Author and article information

                Contributors
                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Infect. Microbiol.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                20 June 2017
                2017
                : 7
                : 276
                Affiliations
                [1] 1Research Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky Krasnoyarsk, Russia
                [2] 2Department of Paediatrics, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky Krasnoyarsk, Russia
                [3] 3Department of Children Infectious Diseases, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky Krasnoyarsk, Russia
                Author notes

                Edited by: Ingar Olsen, University of Oslo, Norway

                Reviewed by: Judith Miklossy, Prevention Alzheimer International Foundation, Switzerland; Frank C. Gibson III, University of Florida, United States; Alan Paul Hudson, Wayne State University School of Medicine, United States

                *Correspondence: Abolghasem Tohidpour a.tohidpour@ 123456gmail.com
                Article
                10.3389/fcimb.2017.00276
                5476750
                28676848
                dfbc6abb-7b84-44dd-bb69-23b000ccbadb
                Copyright © 2017 Tohidpour, Morgun, Boitsova, Malinovskaya, Martynova, Khilazheva, Kopylevich, Gertsog and Salmina.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 12 April 2017
                : 06 June 2017
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 211, Pages: 17, Words: 14756
                Funding
                Funded by: Russian Foundation for Basic Research 10.13039/501100002261
                Award ID: 16-44-243073
                Funded by: President of Russian Federation
                Award ID: 10241.2016.7
                Categories
                Microbiology
                Review

                Infectious disease & Microbiology
                infectious diseases,blood-brain barrier,immune response,neurodegeneration,brain development

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