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      The “Aging Factor” Eotaxin-1 (CCL11) Is Detectable in Transfusion Blood Products and Increases with the Donor’s Age

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          Abstract

          Background: High blood levels of the chemokine eotaxin-1 (CCL11) have recently been associated with aging and dementia, as well as impaired memory and learning in humans. Importantly, eotaxin-1 was shown to pass the blood-brain-barrier (BBB) and has been identified as crucial mediator of decreased neurogenesis and cognitive impairment in young mice after being surgically connected to the vessel system of old animals in a parabiosis model. It thus has to be assumed that differences in eotaxin-1 levels between blood donors and recipients might influence cognitive functions also in humans. However, it is unknown if eotaxin-1 is stable during processing and storage of transfusion blood components. This study assesses eotaxin-1 concentrations in fresh-frozen plasma (FFP), erythrocyte concentrate (EC), and platelet concentrate (PC) in dependence of storage time as well as the donor’s age and gender.

          Methods: Eotaxin-1 was measured in FFP ( n = 168), EC ( n = 160) and PC ( n = 8) ready-to-use for transfusion employing a Q-Plex immunoassay for eotaxin-1. Absolute quantification of eotaxin-1 was performed with Q-view software.

          Results: Eotaxin-1 was consistently detected at a physiological level in FFP and EC but not PC. Eotaxin-1 levels were comparable in male and female donors but increased significantly with rising age of donors in both, FFP and EC. Furthermore, eotaxin-1 was not influenced by storage time of either blood component. Finally, eotaxin-1 is subject to only minor fluctuations within one donor over a longer period of time.

          Conclusion: Eotaxin-1 is detectable and stable in FFP and EC and increases with donor’s age. Considering the presumed involvement in aging and cognitive malfunction, differences in donor- and recipient eotaxin-1 levels might affect mental factors after blood transfusion.

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          Most cited references30

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          Resolving postoperative neuroinflammation and cognitive decline.

          Cognitive decline accompanies acute illness and surgery, especially in the elderly. Surgery engages the innate immune system that launches a systemic inflammatory response that, if unchecked, can cause multiple organ dysfunction. We sought to understand the mechanisms whereby the brain is targeted by the inflammatory response and how this can be resolved. C57BL/6J, Ccr2(RFP/+)Cx3cr1(GFP/+), Ikk(F/F) mice and LysM-Cre/Ikk(F/F) mice underwent stabilized tibial fracture operation under analgesia and general anesthesia. Separate cohorts of mice were tested for systemic and hippocampal inflammation, integrity of the blood-brain barrier (BBB), and cognition. The putative resolving effects of the cholinergic pathway on these postoperative responses were also studied. Peripheral surgery disrupts the BBB via release of tumor necrosis factor-alpha (TNFα), which facilitates the migration of macrophages into the hippocampus. Macrophage-specific deletion of Ikappa B kinase (IKK)β, a central coordinator of TNFα signaling through activation of nuclear factor (NF) κB, prevents BBB disruption and macrophage infiltration in the hippocampus following surgery. Activation of the α7 subtype of nicotinic acetylcholine receptors, an endogenous inflammation-resolving pathway, prevents TNFα-induced NF-κB activation, macrophage migration into the hippocampus, and cognitive decline following surgery. These data reveal the mechanisms for bidirectional communication between the brain and immune system following aseptic trauma. Pivotal molecular mechanisms can be targeted to prevent and/or resolve postoperative neuroinflammation and cognitive decline. Copyright © 2011 American Neurological Association.
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            Postoperative delirium and cognitive dysfunction.

            Postoperative delirium and cognitive dysfunction (POCD) are topics of special importance in the geriatric surgical population. They are separate entities, whose relationship has yet to be fully elucidated. Although not limited to geriatric patients, the incidence and impact of both are more profound in geriatric patients. Delirium has been shown to be associated with longer and more costly hospital course and higher likelihood of death within 6 months or postoperative institutionalization. POCD has been associated with increased mortality, risk of leaving the labour market prematurely, and dependency on social transfer payments. Here, we review their definitions and aetiology, and discuss treatment and prevention in elderly patients undergoing major non-cardiac surgery. Good basic care demands identification of at-risk patients, awareness of common perioperative aggravating factors, simple prevention interventions, recognition of the disease states, and basic treatments for patients with severe hyperactive manifestations.
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              Chemokines: a new class of neuromodulator?

              Chemokines are not only found in the immune system or expressed in inflammatory conditions: they are constitutively present in the brain in both glial cells and neurons. Recently, the possibility has been raised that they might act as neurotransmitters or neuromodulators. Although the evidence is incomplete, emerging data show that chemokines have several of the characteristics that define neurotransmitters. Moreover, their physiological actions resemble those of neuromodulators in the sense that chemokines usually have few effects by themselves in basal conditions, but modify the induced release of neurotransmitters or neuropeptides. These findings, together with the pharmacological development of agonists and antagonists that are selective for chemokine receptors and can cross the blood-brain barrier, open a new era of research in neuroscience.
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                Author and article information

                Contributors
                Journal
                Front Aging Neurosci
                Front Aging Neurosci
                Front. Aging Neurosci.
                Frontiers in Aging Neuroscience
                Frontiers Media S.A.
                1663-4365
                01 December 2017
                2017
                : 9
                : 402
                Affiliations
                [1] 1Experimental Urology, Department of Urology, Medical University of Innsbruck , Innsbruck, Austria
                [2] 2Department of Anesthesiology and Critical Care Medicine, University Hospital of Innsbruck , Innsbruck, Austria
                [3] 3Central Institute for Blood Transfusion and Immunological Department, University Hospital of Innsbruck , Innsbruck, Austria
                Author notes

                Edited by: Aurel Popa-Wagner, University of Rostock, Germany

                Reviewed by: Jian Luo, Palo Alto Veterans Institute for Research, Inc. (PAVIR), United States; Rongqiao He, State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics (CAS), China

                *Correspondence: Julia Hoefer julia.hoefer@ 123456i-med.ac.at

                These authors have contributed equally to this work.

                Article
                10.3389/fnagi.2017.00402
                5717008
                29249965
                1cd03452-5936-483d-bb6b-31071770157b
                Copyright © 2017 Hoefer, Luger, Dal-Pont, Culig, Schennach and Jochberger.

                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
                : 22 September 2017
                : 21 November 2017
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 37, Pages: 8, Words: 5304
                Funding
                Funded by: Austrian Science Fund 10.13039/501100002428
                Award ID: T 738-BBL
                Categories
                Neuroscience
                Original Research

                Neurosciences
                eotaxin-1,aging,cognitive function,blood components,blood transfusion,age
                Neurosciences
                eotaxin-1, aging, cognitive function, blood components, blood transfusion, age

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