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      Clinical Interventions in Aging (submit here)

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      Effect of IL-6 and hsCRP Serum Levels on Functional Prognosis in Stroke Patients Undergoing IV-Thrombolysis: Retrospective Analysis

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          Abstract

          Purpose

          We evaluated the relationship between pretreatment IL-6 and hsCRP levels, symptom severity and functional outcome of patients with acute ischemic stroke (AIS) treated with IV-thrombolysis.

          Patients and Methods

          IL-6 and hsCRP samples were obtained from 83 consecutively treated Caucasian patients with AIS prior to initiation of IV-thrombolysis. Severity of stroke symptoms was assessed using the National Institutes of Health Stroke Scale (NIHSS), whereas functional outcome was assessed with modified Rankin Scale (mRS). The commercially available sets of enzymatic immune tests were used to estimate the concentrations of inflammatory markers in serum.

          Results

          Medians of IL-6 serum concentrations prior to IV-thrombolysis were lower in patients with favorable (mRS 0–2 pts) functional outcome than in those with unfavorable (mRS 3–6 pts) functional outcome, both at hospital dismission (5.92: 2.30–7.71 vs 9.46: 3.79–17.29 pg/mL; p<0.01) and on the ninetieth day from stroke onset (5.87: 2.30–10.58 vs 10.9: 5.94–17.28 pg/mL; p<0.01). There were no existing differences regarding hsCRP levels between groups (2.49: 0.11–9.82 vs 4.44: 0.32–9.87 mg/dL; p=0.30 and 2.57: 0.11–2.57 vs 2.83: 0.32–9.32 mg/dL; p=0.75, respectively). Patients with lacunar strokes were characterized by lower median of IL-6 (5.96: 2.87–13.0% vs 7.29: 2.30–17.28; p=<0.02) and hsCRP (2.25: 0.11–9.82 vs 4.84: 0.35–9.87; p=0.01) than those with nonlacunar infarctions. Multivariate analysis showed an impact of IL-6 on mRS measured on hospital dismission and after three months, regardless of their initial NIHSS, presence of hemorrhagic transformation and type 2 diabetes. No impact of hsCRP, lacunar etiology and patients’ age on functional outcome existed.

          Conclusion

          Regardless of the stroke etiology, pretreatment of IL-6, but not of hsCRP levels, may help to predict functional outcome after IV-thrombolysis independently of symptom severity and stroke complications.

          Most cited references45

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          2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

          The purpose of these guidelines is to provide an up-to-date comprehensive set of recommendations for clinicians caring for adult patients with acute arterial ischemic stroke in a single document. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators. These guidelines supersede the 2013 guidelines and subsequent updates.
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            An early and sustained peripheral inflammatory response in acute ischaemic stroke: relationships with infection and atherosclerosis.

            Central nervous system and peripheral inflammation is important in the responses to ischaemic stroke, and may also predispose to its development. We aimed to identify (1) the extent to which a peripheral inflammatory response is activated in patients following acute stroke, and (2) whether there was evidence for preexisting peripheral inflammation. Thirty-six patients with ischaemic stroke within 12 h of onset of symptoms had serial blood samples taken up to 12 months for analysis of markers of inflammation. Thirty-six control subjects, individually matched for age, sex and degree of atherosclerosis, were also studied. Median C-reactive protein (CRP) was elevated, relative to controls (2.08 mg/l), from admission (4.31 mg/l) (p
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              Essential role of interleukin-6 in post-stroke angiogenesis.

              Ambivalent effects of interleukin-6 on the pathogenesis of ischaemic stroke have been reported. However, to date, the long-term actions of interleukin-6 after stroke have not been investigated. Here, we subjected interleukin-6 knockout (IL-6(-/-)) and wild-type control mice to mild brain ischaemia by 30-min filamentous middle cerebral artery occlusion/reperfusion. While ischaemic tissue damage was comparable at early time points, IL-6(-/-) mice showed significantly increased chronic lesion volumes as well as worse long-term functional outcome. In particular, IL-6(-/-) mice displayed an impaired angiogenic response to brain ischaemia with reduced numbers of newly generated endothelial cells and decreased density of perfused microvessels along with lower absolute regional cerebral blood flow and reduced vessel responsivity in ischaemic striatum at 4 weeks. Similarly, the early genomic activation of angiogenesis-related gene networks was strongly reduced and the ischaemia-induced signal transducer and activator of transcription 3 activation observed in wild-type mice was almost absent in IL-6(-/-) mice. In addition, systemic neoangiogenesis was impaired in IL-6(-/-) mice. Transplantation of interleukin-6 competent bone marrow into IL-6(-/-) mice (IL-6(chi)) did not rescue interleukin-6 messenger RNA expression or the early transcriptional activation of angiogenesis after stroke. Accordingly, chronic stroke outcome in IL-6(chi) mice recapitulated the major effects of interleukin-6 deficiency on post-stroke regeneration with significantly enhanced lesion volumes and reduced vessel densities. Additional in vitro experiments yielded complementary evidence, which showed that after stroke resident brain cells serve as the major source of interleukin-6 in a self-amplifying network. Treatment of primary cortical neurons, mixed glial cultures or immortalized brain endothelia with interleukin 6-induced robust interleukin-6 messenger RNA transcription in each case, whereas oxygen-glucose deprivation did not. However, oxygen-glucose deprivation of organotypic brain slices resulted in strong upregulation of interleukin-6 messenger RNA along with increased transcription of key angiogenesis-associated genes. In conclusion, interleukin-6 produced locally by resident brain cells promotes post-stroke angiogenesis and thereby affords long-term histological and functional protection.
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                Author and article information

                Journal
                Clin Interv Aging
                Clin Interv Aging
                cia
                clinintag
                Clinical Interventions in Aging
                Dove
                1176-9092
                1178-1998
                06 August 2020
                2020
                : 15
                : 1295-1303
                Affiliations
                [1 ]Department of Medical Biology and Biochemistry, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń , Bydgoszcz, Poland
                [2 ]Department of Cardiology and Clinical Pharmacology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń , Bydgoszcz, Poland
                [3 ]Department of Geriatrics, Division of Biochemistry and Biogerontology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń , Bydgoszcz, Poland
                [4 ]Department of Neurology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń , Bydgoszcz, Poland
                [5 ]Department of Neurology and Stroke Unit, Holy Spirit Specialist Hospital in Sandomierz, Jan Kochanowski University , Kielce, Poland
                [6 ]Medical Stimulation Center, Medical University of Gdańsk , Gdańsk, Poland
                Author notes
                Correspondence: Hanna Pawluk Department of Medical Biology and Biochemistry, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń , Karłowicza 24, Bydgoszcz85–092, PolandTel +48 52 585 37 55 Email hannapawluk1@wp.pl
                Author information
                http://orcid.org/0000-0001-9949-5215
                http://orcid.org/0000-0002-7277-721X
                http://orcid.org/0000-0002-6988-3038
                http://orcid.org/0000-0003-4646-1702
                http://orcid.org/0000-0001-6237-521X
                http://orcid.org/0000-0001-7704-2434
                Article
                258381
                10.2147/CIA.S258381
                7418453
                32821090
                8607db42-7664-45f1-b324-7bc98779c270
                © 2020 Pawluk et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 15 April 2020
                : 08 July 2020
                Page count
                Figures: 2, Tables: 6, References: 51, Pages: 9
                Categories
                Original Research

                Health & Social care
                inflammatory markers,ischemic stroke,thrombolysis,old age diseases
                Health & Social care
                inflammatory markers, ischemic stroke, thrombolysis, old age diseases

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