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      Neuroinflammation and Perioperative Neurocognitive Disorders

      research-article
        , PhD 1 , , PhD 1 ,
      Anesthesia and Analgesia
      Lippincott Williams & Wilkins

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          Abstract

          Neuroinflammation has become a key hallmark of neurological complications including perioperative pathologies such as postoperative delirium and longer-lasting postoperative cognitive dysfunction. Dysregulated inflammation and neuronal injury are emerging from clinical studies as key features of perioperative neurocognitive disorders. These findings are paralleled by a growing body of preclinical investigations aimed at better understanding how surgery and anesthesia affect the central nervous system and possibly contribute to cognitive decline. Herein, we review the role of postoperative neuroinflammation and underlying mechanisms in immune-to-brain signaling after peripheral surgery.

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          The Microglial Sensome Revealed by Direct RNA Sequencing

          Microglia, the principal neuroimmune sentinels of the brain, continuously sense changes in their environment and respond to invading pathogens, toxins and cellular debris. Microglia exhibit plasticity and can assume neurotoxic or neuroprotective priming states that determine their responses to danger. We used direct RNA sequencing, without amplification or cDNA synthesis, to determine the quantitative transcriptomes of microglia of healthy adult and aged mice. We validated our findings by fluorescent dual in-situ hybridization, unbiased proteomic analysis and quantitative PCR. We report here that microglia have a distinct transcriptomic signature and express a unique cluster of transcripts encoding proteins for sensing endogenous ligands and microbes that we term the “sensome”. With aging, sensome transcripts for endogenous ligand recognition are downregulated, whereas those involved in microbe recognition and host defense are upregulated. In addition, aging is associated with an overall increase in expression of microglial genes involved in neuroprotection.
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            Ageing, neurodegeneration and brain rejuvenation.

            Although systemic diseases take the biggest toll on human health and well-being, increasingly, a failing brain is the arbiter of a death preceded by a gradual loss of the essence of being. Ageing, which is fundamental to neurodegeneration and dementia, affects every organ in the body and seems to be encoded partly in a blood-based signature. Indeed, factors in the circulation have been shown to modulate ageing and to rejuvenate numerous organs, including the brain. The discovery of such factors, the identification of their origins and a deeper understanding of their functions is ushering in a new era in ageing and dementia research.
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              Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice.

              As human lifespan increases, a greater fraction of the population is suffering from age-related cognitive impairments, making it important to elucidate a means to combat the effects of aging. Here we report that exposure of an aged animal to young blood can counteract and reverse pre-existing effects of brain aging at the molecular, structural, functional and cognitive level. Genome-wide microarray analysis of heterochronic parabionts--in which circulatory systems of young and aged animals are connected--identified synaptic plasticity-related transcriptional changes in the hippocampus of aged mice. Dendritic spine density of mature neurons increased and synaptic plasticity improved in the hippocampus of aged heterochronic parabionts. At the cognitive level, systemic administration of young blood plasma into aged mice improved age-related cognitive impairments in both contextual fear conditioning and spatial learning and memory. Structural and cognitive enhancements elicited by exposure to young blood are mediated, in part, by activation of the cyclic AMP response element binding protein (Creb) in the aged hippocampus. Our data indicate that exposure of aged mice to young blood late in life is capable of rejuvenating synaptic plasticity and improving cognitive function.
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                Author and article information

                Journal
                Anesth Analg
                Anesth. Analg
                ANE
                Anesthesia and Analgesia
                Lippincott Williams & Wilkins
                0003-2999
                1526-7598
                April 2019
                19 March 2019
                : 128
                : 4
                : 781-788
                Affiliations
                [1]From the Center for Translational Pain Medicine, Department of Anesthe siology, Duke University Medical Center, Durham, North Carolina.
                Author notes
                Address correspondence to Niccolò Terrando, PhD, Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, 3 Genome Ct, MSRBIII Room 6144, Durham, NC 27710. Address e-mail to niccolo.terrando@ 123456duke.edu .
                Article
                00023
                10.1213/ANE.0000000000004053
                6437083
                30883423
                7e280faf-51e4-42f8-8872-1bb96d485ffe
                Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.

                This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 31 December 2018
                Categories
                Neuroscience and Neuroanesthesiology
                Narrative Review Article
                Custom metadata
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