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      Anti-inflammatory Effects of Perioperative Dexmedetomidine Administered as an Adjunct to General Anesthesia: A Meta-analysis

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          Abstract

          The aim of this meta-analysis is to examine the effects of dexmedetomidine on serum inflammatory markers when administered perioperatively. We searched multiple electronic databases for relevant research papers, and carried out meta-analyses of weighted mean differences and interpreted in the light of statistical heterogeneity (I 2). Fifteen RCTs recruiting 641 patients were included. Dexmedetomidine treatment significantly decreased interleukin-6 (IL-6), IL-8 and tumor necrosis factor-alpha (TNF-α) levels with mean differences [95% CI] in the changes from baseline between dexmedetomidine treated and controls of −25.14 [−35.29, −15.00]; P < 0.00001 (for IL-6), −5.69 [−10.77, −0.60]; P < 0.04 (for IL-8), and −20.30 [−30.93, −9.67]; P < 0.0002 (for TNF-α) immediately after surgery; and −41.55 [−57.41, −25.70]; P < 0.00001 (IL-6), −6.46 [−10.83, −2.08]; P < 0.005 (IL-8), and −14.67 [−22.61, −6.73]; P < 0.0003 (TNF-α) on postoperative day 1 (random effects). IL-10 levels were found to increase significantly a day after surgery (8.33 [3.31, 13.36]; P = 0.001). Subgroup analyses did not reveal significant differences. In conclusion, perioperative adjunctive use of dexmedetomidine substantially decreases serum IL-6, IL-8 and TNF-α levels.

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          Inflammation in wound repair: molecular and cellular mechanisms.

          In post-natal life the inflammatory response is an inevitable consequence of tissue injury. Experimental studies established the dogma that inflammation is essential to the establishment of cutaneous homeostasis following injury, and in recent years information about specific subsets of inflammatory cell lineages and the cytokine network orchestrating inflammation associated with tissue repair has increased. Recently, this dogma has been challenged, and reports have raised questions on the validity of the essential prerequisite of inflammation for efficient tissue repair. Indeed, in experimental models of repair, inflammation has been shown to delay healing and to result in increased scarring. Furthermore, chronic inflammation, a hallmark of the non-healing wound, predisposes tissue to cancer development. Thus, a more detailed understanding in mechanisms controlling the inflammatory response during repair and how inflammation directs the outcome of the healing process will serve as a significant milestone in the therapy of pathological tissue repair. In this paper, we review cellular and molecular mechanisms controlling inflammation in cutaneous tissue repair and provide a rationale for targeting the inflammatory phase in order to modulate the outcome of the healing response.
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            Tumor Necrosis Factor Alpha: A Link between Neuroinflammation and Excitotoxicity

            Tumor necrosis factor alpha (TNF- α ) is a proinflammatory cytokine that exerts both homeostatic and pathophysiological roles in the central nervous system. In pathological conditions, microglia release large amounts of TNF- α ; this de novo production of TNF- α is an important component of the so-called neuroinflammatory response that is associated with several neurological disorders. In addition, TNF- α can potentiate glutamate-mediated cytotoxicity by two complementary mechanisms: indirectly, by inhibiting glutamate transport on astrocytes, and directly, by rapidly triggering the surface expression of Ca+2 permeable-AMPA receptors and NMDA receptors, while decreasing inhibitory GABAA receptors on neurons. Thus, the net effect of TNF- α is to alter the balance of excitation and inhibition resulting in a higher synaptic excitatory/inhibitory ratio. This review summarizes the current knowledge of the cellular and molecular mechanisms by which TNF- α links the neuroinflammatory and excitotoxic processes that occur in several neurodegenerative diseases, but with a special emphasis on amyotrophic lateral sclerosis (ALS). As microglial activation and upregulation of TNF- α expression is a common feature of several CNS diseases, as well as chronic opioid exposure and neuropathic pain, modulating TNF- α signaling may represent a valuable target for intervention.
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              Evidence for a cytokine model of cognitive function.

              Aiming at a formulation of a cytokine model of cognitive function under immunologically unchallenged physiological conditions, this article reviews the cytokine biology in the central nervous system (CNS) and recent developments in normal cytokine functions within the CNS that subserve cognitive processes. Currently available evidence shows that the cytokines IL-1beta, IL-6 and TNF-alpha play a role in complex cognitive processes at the molecular level, such as synaptic plasticity, neurogenesis, as well as neuromodulation. Such findings provide evidence for a cytokine model of cognitive function, which shows that cytokines play an intimate role in the molecular and cellular mechanisms subserving learning, memory and cognition under physiological conditions. These cytokine-mediated cognitive processes have implications in the long-term development and pathogenesis of specific neuropsychiatric disorders such as major depression and dementia. The identification of this central role of cytokines in various brain activities during health provides greater insight into normal brain functions, especially synaptic plasticity, memory and cognition, and facilitates the understanding of specific biological mechanisms involved in neuropsychiatric diseases, such as dementia and depression. In order to extend the suggested cytokine model of cognitive function onto other members of the cytokine family, future research is required to investigate the physiological effects of other cytokines such as interferon-gamma (IFNgamma), alpha(1)-antichymotrypsin and IL-2 on cognitive function at the molecular level under immunologically unchallenged conditions.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                21 July 2015
                2015
                : 5
                : 12342
                Affiliations
                [1 ]Department of Anesthesiology, Jinan General Hospital, PLA Jinan Military Area Command , Jinan 250031, Shandong, China
                [2 ]Department of Anesthesiology, The First Affiliated Hospital of Jinan University , Guangzhou 510632, Guangdong, China
                [3 ]Department of Radiology , No. 261 Hospital of PLA, Beijing, China
                [4 ]Department of Anesthesiology, The People’s Hospital of Zhangqiu , Zhangqiu 250200, Henan, China
                [5 ]Department of Anesthesiology , Yancheng City No.1 People’s Hospital, Yancheng 224005, Jiangsu, China
                Author notes
                [*]

                These authors equally contributed to this work.

                Article
                srep12342
                10.1038/srep12342
                4508837
                26196332
                ddc4bdb5-4675-470a-bdd4-7aae7639f9e0
                Copyright © 2015, Macmillan Publishers Limited

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 07 August 2014
                : 24 June 2015
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