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      Serum melatonin levels are associated with mortality in patients with malignant middle cerebral artery infarction

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          Abstract

          Objectives

          Lower serum melatonin levels are found in patients with ischaemic stroke compared with healthy controls. This study aimed to determine whether serum melatonin levels are associated with peroxidation status, antioxidant status, and mortality in patients with ischaemic stroke.

          Methods

          Patients with severe malignant middle cerebral artery infarction (MMCAI), defined as a Glasgow coma scale (GCS) score lower than 9, were included. Serum levels of melatonin, malondialdehyde (to assess lipid peroxidation), and total antioxidant capacity at the time of diagnosing MMCAI were determined. We chose 30-day mortality as the endpoint of the study.

          Results

          We found significantly higher serum levels of melatonin, total antioxidant capacity, and malondialdehyde in non-survivors (n = 32) than in survivors (n = 32) with MMCAI. Serum melatonin levels were associated with 30-day mortality (odds ratio = 2.205; 95% confidence interval = 1.294–3.759) after controlling for GCS score and age. We found a positive association between serum melatonin levels and total antioxidant capacity (rho = 0.36), and between serum melatonin and malondialdehyde levels (rho = 0.35).

          Conclusions

          Our study shows that serum melatonin levels are associated with peroxidation status, antioxidant status, and mortality in patients with MMCAI.

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          Most cited references33

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          Malondialdehyde determination as index of lipid peroxidation.

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            The role of inflammation in CNS injury and disease.

            For many years, the central nervous system (CNS) was considered to be 'immune privileged', neither susceptible to nor contributing to inflammation. It is now appreciated that the CNS does exhibit features of inflammation, and in response to injury, infection or disease, resident CNS cells generate inflammatory mediators, including proinflammatory cytokines, prostaglandins, free radicals and complement, which in turn induce chemokines and adhesion molecules, recruit immune cells, and activate glial cells. Much of the key evidence demonstrating that inflammation and inflammatory mediators contribute to acute, chronic and psychiatric CNS disorders is summarised in this review. However, inflammatory mediators may have dual roles, with detrimental acute effects but beneficial effects in long-term repair and recovery, leading to complications in their application as novel therapies. These may be avoided in acute diseases in which treatment administration might be relatively short-term. Targeting interleukin (IL)-1 is a promising novel therapy for stroke and traumatic brain injury, the naturally occurring antagonist (IL-1ra) being well tolerated by rheumatoid arthritis patients. Chronic disorders represent a greater therapeutic challenge, a problem highlighted in Alzheimer's disease (AD); significant data suggested that anti-inflammatory agents might reduce the probability of developing AD, or slow its progression, but prospective clinical trials of nonsteroidal anti-inflammatory drugs or cyclooxygenase inhibitors have been disappointing. The complex interplay between inflammatory mediators, ageing, genetic background, and environmental factors may ultimately regulate the outcome of acute CNS injury and progression of chronic neurodegeneration, and be critical for development of effective therapies for CNS diseases.
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              Oxidants, antioxidants and the ischemic brain.

              Despite numerous defenses, the brain is vulnerable to oxidative stress resulting from ischemia/reperfusion. Excitotoxic stimulation of superoxide and nitric oxide production leads to formation of highly reactive products, including peroxynitrite and hydroxyl radical, which are capable of damaging lipids, proteins and DNA. Use of transgenic mutants and selective pharmacological antioxidants has greatly increased understanding of the complex interplay between substrate deprivation and ischemic outcome. Recent evidence that reactive oxygen/nitrogen species play a critical role in initiation of apoptosis, mitochondrial permeability transition and poly(ADP-ribose) polymerase activation provides additional mechanisms for oxidative damage and new targets for post-ischemic therapeutic intervention. Because oxidative stress involves multiple post-ischemic cascades leading to cell death, effective prevention/treatment of ischemic brain injury is likely to require intervention at multiple effect sites.
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                Author and article information

                Journal
                J Int Med Res
                J. Int. Med. Res
                IMR
                spimr
                The Journal of International Medical Research
                SAGE Publications (Sage UK: London, England )
                0300-0605
                1473-2300
                30 May 2018
                August 2018
                : 46
                : 8
                : 3268-3277
                Affiliations
                [1 ]Intensive Care Unit, Hospital Universitario de Canarias, Ofra s/n, La Laguna, Santa Cruz de Tenerife, Spain
                [2 ]Intensive Care Unit, Hospital Universitario Nuestra Señora de Candelaria, Crta del Rosario s/n, Santa Cruz de Tenerife, Spain
                [3 ]Department of Physiology, Faculty of Medicine, University of the La Laguna, Ofra s/n, La Laguna, Santa Cruz de Tenerife, Spain
                [4 ]Laboratory Department, Hospital Universitario de Canarias, Ofra s/n, La Laguna, Tenerife, Spain
                [5 ]Intensive Care Unit, Hospital General La Palma, Buenavista de Arriba s/n, Breña Alta, La Palma, Spain
                [6 ]Intensive Care Unit, Hospital Clínico Universitario de Valencia, Avda, Blasco Ibáñez n°17-19, Valencia, Spain
                [7 ]Intensive Care Unit, Hospital Universitario Dr. Negrín, CIBERES, Barranco de la Ballena s/n, Las Palmas de Gran Canaria, Spain
                [8 ]Intensive Care Unit, Hospital Insular, Plaza Dr. Pasteur s/n, Las Palmas de Gran Canaria, Spain
                [9 ]Research Unit, Hospital Universitario de Canarias, Ofra s/n, La Laguna, Santa Cruz de Tenerife, Spain
                [10 ]Department of Neurosurgery, Hospital Universitario de Canarias, Ofra s/n, La Laguna, Santa Cruz de Tenerife, Spain
                Author notes
                [*]Leonardo Lorente, Intensive Care Unit, Hospital Universitario de Canarias, Ofra s/n, La Laguna, Tenerife, Spain. Email: lorentemartin@ 123456msn.com
                Author information
                https://orcid.org/0000-0003-4902-4065
                Article
                10.1177_0300060518775008
                10.1177/0300060518775008
                6134645
                29848129
                70582273-e79c-4c0c-9c71-c1fac6cc020c
                © The Author(s) 2018

                Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 16 December 2017
                : 15 April 2018
                Funding
                Funded by: Instituto de Salud Carlos III (Madrid, Spain) co-financed with Fondo Europeo de Desarrollo Regional (FEDER), FundRef ;
                Award ID: INT16/00165
                Funded by: Grupo de Expertos Neurológicos de Canarias (GEN-Canarias. Santa Cruz de Tenerife. Spain), FundRef ;
                Categories
                Clinical Research Reports

                melatonin,cerebral infarction,mortality,stroke,malondialdehyde,antioxidant capacity

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