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      Neuroinflammation and Cerebrovascular Disease in Old Age: A Translational Medicine Perspective

      review-article
      1, 2 , * , 3
      Journal of Aging Research
      SAGE-Hindawi Access to Research

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          Abstract

          The incidence of cerebrovascular disease is highest in the elderly population. However, the pathophysiological mechanisms of brain response to cerebral ischemia in old age are currently poorly understood. Ischemic changes in the commonly used young animal stroke models do not reflect the molecular changes associated with the aged brain. Neuroinflammation and oxidative stress are important pathogenic processes occurring during the acute phase of cerebral ischemia. Free radical generation is also implicated in the aging process, and the combination of these effects in elderly stroke patients could explain the higher risk of morbidity and mortality. A better understanding of stroke pathophysiology in the elderly patient would assist in the development of new therapeutic strategies for this vulnerable age group. With the increasing use of reperfusion therapies, inflammatory pathways and oxidative stress remain attractive therapeutic targets for the development of adjuvant neuroprotective agents. This paper will discuss these molecular aspects of acute stroke and senescence from a bench-to-bedside research perspective.

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          Most cited references257

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          Adverse events associated with testosterone administration.

          Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men. The safety and efficacy of testosterone treatment in older men who have limitations in mobility have not been studied. Community-dwelling men, 65 years of age or older, with limitations in mobility and a total serum testosterone level of 100 to 350 ng per deciliter (3.5 to 12.1 nmol per liter) or a free serum testosterone level of less than 50 pg per milliliter (173 pmol per liter) were randomly assigned to receive placebo gel or testosterone gel, to be applied daily for 6 months. Adverse events were categorized with the use of the Medical Dictionary for Regulatory Activities classification. The data and safety monitoring board recommended that the trial be discontinued early because there was a significantly higher rate of adverse cardiovascular events in the testosterone group than in the placebo group. A total of 209 men (mean age, 74 years) were enrolled at the time the trial was terminated. At baseline, there was a high prevalence of hypertension, diabetes, hyperlipidemia, and obesity among the participants. During the course of the study, the testosterone group had higher rates of cardiac, respiratory, and dermatologic events than did the placebo group. A total of 23 subjects in the testosterone group, as compared with 5 in the placebo group, had cardiovascular-related adverse events. The relative risk of a cardiovascular-related adverse event remained constant throughout the 6-month treatment period. As compared with the placebo group, the testosterone group had significantly greater improvements in leg-press and chest-press strength and in stair climbing while carrying a load. In this population of older men with limitations in mobility and a high prevalence of chronic disease, the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events. The small size of the trial and the unique population prevent broader inferences from being made about the safety of testosterone therapy. (ClinicalTrials.gov number, NCT00240981.) 2010 Massachusetts Medical Society
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            Central nervous system injury-induced immune deficiency syndrome.

            Infections are a leading cause of morbidity and mortality in patients with acute CNS injury. It has recently become clear that CNS injury significantly increases susceptibility to infection by brain-specific mechanisms: CNS injury induces a disturbance of the normally well balanced interplay between the immune system and the CNS. As a result, CNS injury leads to secondary immunodeficiency - CNS injury-induced immunodepression (CIDS) - and infection. CIDS might serve as a model for the study of the mechanisms and mediators of brain control over immunity. More importantly, understanding CIDS will allow us to work on developing effective therapeutic strategies, with which the outcome after CNS damage by a host of diseases could be improved by eliminating a major determinant of poor recovery.
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              Inflammatory markers in population studies of aging.

              To review findings from major epidemiologic studies regarding risk factors for and consequences of elevated markers of inflammation in older adults. Most large, current epidemiologic studies of older adults have measured serum interleukin-6 (IL-6), C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-alpha) and some studies also include more extensive batteries of measures including soluble receptors. There are few defined risk factors for the modest elevations in inflammatory markers seen with aging. These include visceral adiposity, lower sex steroid hormones, smoking, depression and periodontal disease. Of the markers assessed, IL-6 is most robustly associated with incident disease, disability and mortality. Though correlated with age, the etiology of elevated inflammatory markers remains incompletely defined. Inflammation, especially IL-6 may be a common cause of multiple age-related diseases or a final common pathway by which disease leads to disability and adverse outcomes in older adults. Future research targeting inflammation should examine these pathways. Copyright © 2011. Published by Elsevier B.V.
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                Author and article information

                Journal
                J Aging Res
                JAR
                Journal of Aging Research
                SAGE-Hindawi Access to Research
                2090-2204
                2090-2212
                2011
                31 October 2011
                : 2011
                : 857484
                Affiliations
                1Neurological Service, San Camillo de'Lellis General Hospital, 02100 Rieti, Italy
                2Neurological Section, SMDN-Center for Cardiovascular Medicine and Cerebrovascular Disease Prevention, 67039 Sulmona (AQ), Italy
                3Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, Scotland G4 0RE, UK
                Author notes

                Academic Editor: Aurel Popa-Wagner

                Article
                10.4061/2011/857484
                3205617
                22132330
                b9bc0d24-eb65-4fa2-a601-feb10e54c85d
                Copyright © 2011 M. Di Napoli and I. M. Shah.

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

                History
                : 26 April 2011
                : 10 August 2011
                Categories
                Review Article

                Molecular medicine
                Molecular medicine

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