Cytokine Registry In Stroke Patients (CRISP): Protocol of a prospective observational study

Mudassir Farooqui, Asad Ikram, Sajid Suriya, Sidra Saleem, Syed A Quadri, Myranda Robinson, Santiago Ortega-Gutierrez, Fares Qeadan, Enrique Leira, Surojit Paul, Atif Zafar, Mudassir Farooqui, Asad Ikram, Sajid Suriya, Sidra Saleem, Syed A Quadri, Myranda Robinson, Santiago Ortega-Gutierrez, Fares Qeadan, Enrique Leira, Surojit Paul, Atif Zafar

Abstract

Inflammation is an important pathophysiological process after an acute stroke (AS). Pro- and anti-inflammatory molecules (cytokines and interleukins) are the key players during this mechanism. Emerging evidence indicate that these molecules can serve as biomarkers of stroke progression and outcome and as novel therapeutics agents. The aim of this study is to explore the temporal changes in these molecules and validate them as biomarker of AS progression and neurological outcome.The "Cytokine Registry In Stroke Patients (CRISP)" is a prospective cohort study of 600 AS patients presenting to the tertiary hospital with-in 24 h of the onset of symptoms. Plasma cytokines and interleukins will be collected at admission and 24 h after and will be measured using enzyme-linked immunosorbent assay (ELISA) to evaluate the difference in their variation among different gender, race and ethnicity and their association with various neurological outcomes. The primary exposures are biological sex (male, female) and race/ethnicity. Confounding variables include age, vascular risk factors, infarct size, stroke onset to presentation time, and identified stroke etiologies. Matched controls will be used for the comparison and evaluation of the difference among gender and race/ethnicities.CRISP is a prospective observational study that investigates the role and relationship of molecular biomarkers identifying specific and relevant targets pertinent for monitoring the progression and outcome in AS patients.Trial Registration: The study is registered on ClinicalTrial.gov: https://ichgcp.net/clinical-trials-registry/NCT03297827" title="See in ClinicalTrials.gov">NCT03297827).

Conflict of interest statement

The authors have no conflicts of interest disclose.

Figures

Figure 1
Figure 1
Schematic representation of the CRISP study trial.

References

    1. Amarenco P, Bogousslavsky J, Caplan L, et al. Classification of stroke subtypes. Cerebrovasc Dis 2009;27:493–501.
    1. Powers WJ, Rabinstein AA, Ackerson T, et al. 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. Stroke 2018;49:e46–99.
    1. W.H. Organization. The top 10 causes of death. World Health Organization, Media Center. World health organization, Media Center; 2016. Available at: . Accessed October 28, 2019.
    1. C.D. Control. Stroke Facts; 2017. Available at: Accessed October 28, 2019.
    1. Benjamin EJ, Virani SS, Callaway CW, et al. Heart disease and stroke statistics-2018 update: a report from the American Heart Association. Circulation 2018;137:e67–492.
    1. Chehaibi K, Trabelsi I, Mahdouani K, et al. Correlation of oxidative stress parameters and inflammatory markers in ischemic stroke patients. J Stroke Cerebrovasc Dis 2016;25:2585–93.
    1. Becker KJ, Yang G, Li G. Inflammation and acute stroke. Curr Opin Neurol 1998;11:45–9.
    1. Jin R, Yang G, Li G. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol 2010;87:779–89.
    1. Fassbender K, Rossol S, Kammer T, et al. Proinflammatory cytokines in serum of patients with acute cerebral ischemia: kinetics of secretion and relation to the extent of brain damage and outcome of disease. J Neurol Sci 1994;122:135–9.
    1. Doll DN, Barr TL, Simpkins JW. Cytokines: their role in stroke and potential use as biomarkers and therapeutic targets. Aging Dis 2014;5:294.
    1. Vila N, Castillo J, Dávalos A, et al. Levels of anti-inflammatory cytokines and neurological worsening in acute ischemic stroke. Stroke 2003;34:671–5.
    1. Oto J, Suzue A, Inui D, et al. Plasma proinflammatory and anti-inflammatory cytokine and catecholamine concentrations as predictors of neurological outcome in acute stroke patients. J Anesth 2008;22:207–12.
    1. Gong C, Hoff JT, Keep RF, et al. Acute inflammatory reaction following experimental intracerebral hemorrhage in rat. Brain Res 2000;871:57–65.
    1. Wang J, Doré SJ. Metabolism. Inflammation after intracerebral hemorrhage. J Cereb Blood Flow Metabol 2007;27:894–908.
    1. Kes VB, Simundic A-M, Nikolac N, et al. Pro-inflammatory and anti-inflammatory cytokines in acute ischemic stroke and their relation to early neurological deficit and stroke outcome. Clin Biochem 2008;41:1330–4.
    1. Silva Y, Leira R, Tejada J, et al. Molecular signatures of vascular injury are associated with early growth of intracerebral hemorrhage. Stroke 2005;36:86–91.
    1. Ferrarese C, Mascarucci P, Zoia C, et al. Increased cytokine release from peripheral blood cells after acute stroke. J Cereb Blood Flow Metabol 1999;19:1004–9.
    1. Lu Y-L, Wang R, Huang H-T, et al. Association of S100B polymorphisms and serum S100B with risk of ischemic stroke in a Chinese population. Sci Rep 2018;8:971.
    1. Delgado P, Alvarez Sabin J, Santamarina E, et al. Plasma S100B level after acute spontaneous intracerebral hemorrhage. Stroke 2006;37:2837–9.
    1. Su EJ, Fredriksson L, Geyer M, et al. Activation of PDGF-CC by tissue plasminogen activator impairs blood-brain barrier integrity during ischemic stroke. Nat Med 2008;14:731.
    1. Matsuo R, Ago T, Kamouchi M, et al. Clinical significance of plasma VEGF value in ischemic stroke-research for biomarkers in ischemic stroke (REBIOS) study. BMC Neurol 2013;13:32.
    1. Harris PA, Taylor R, Thielke R, et al. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42:377–81.
    1. Miller AM. Role of IL-33 in inflammation and disease. J Inflamm 2011;8:22.
    1. Miller AM, Liew FY. The IL-33/ST2 pathway—a new therapeutic target in cardiovascular disease. Pharmacol Ther 2011;131:179–86.

Source: PubMed

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