Document Type : Original Article
Authors
- Fariborz Rezaeitalab 1
- Maryam Esmaeili 1
- Amin Saberi 2
- Zohreh Vahidi 3
- Maryam Emadzadeh 4
- Hamid Reza Rahimi 5
- Niloofar Ramezani 1
- Seyed Zakaria Mirshabani-Toloti 6
1 Department of Neurology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
2 School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
3 School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Inflammation and Inflammatory Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
4 School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Clinical Research Unit, Mashhad University of Medical Sciences, Mashhad, Iran
5 Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
6 Student Research Committee, School of Paramedicine, Mashhad University of Medical Sciences, Mashhad, Iran
Abstract
Background: Inflammatory processes have been proposed in the pathophysiology of ischemic stroke. The present study was designed to evaluate the relationship between tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), IL 1 beta (IL-1β), and high sensitivity C-reactive protein (hsCRP) with the prognosis and functional outcome in patients with less severe ischemic stroke.
Methods: We measured the level of IL-1β, IL-6, hsCRP, and TNF-α on days 1 and 5 after stroke onset by enzyme-linked immunosorbent assay (ELISA). The infarct volume was assessed using Alberta Stroke Program Early CT Score (ASPECTS) and posterior circulation ASPECTS (pcASPECTS) score in brain computed tomography (CT) scan and magnetic resonance imaging (MRI). The severity of stroke was assessed by applying the National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (MRS) in 24 hours on day 5and after 3 months from stroke onset. Good outcome was defined as the third month MRS ≤ 2. The association of inflammatory markers and the course of stroke symptoms over time was examined.
Results: Forty-four first-ever stroke patients without concurrent inflammatory diseases with a mean age of 65 years were included. The mean NIHSS and MRS in admission time were 6.5 ± 3.5 and 3.07, respectively. The day 1 and the day 5 levels of IL-1β, IL-6, hsCRP, and TNF-α were not significantly different in good and poor outcome groups (all P-values > 0.05). In addition, they were not significantly associated with the ASPECTS, pcASPECTS, and changes of NIHSS and MRS over time.
Conclusion: The levels of hsCRP, IL-1β, IL-6, and
TNF-α are not reliable predictors of functional outcomes in patients with less severe acute ischemic stroke (AIS).
Keywords
- Farhoudi M, Mehrvar K, Sadeghi-Bazargani H, Hashemilar M, Seyedi-Vafaee M, Sadeghi-Hokmabad E, et al. Stroke subtypes, risk factors and mortality rate in northwest of Iran. Iran J Neurol 2017; 16(3): 112-7.
- Dregan A, Charlton J, Chowienczyk P, Gulliford MC. Chronic inflammatory disorders and risk of type 2 diabetes mellitus, coronary heart disease, and stroke: A population-based cohort study. Circulation 2014; 130(10): 837-44.
- Zhang YY, Huang NN, Zhao YX, Li YS, Wang D, Fan YC, et al. Elevated tumor necrosis factor-a-induced protein 8-like 2 mRNA from peripheral blood mononuclear cells in patients with acute ischemic stroke. Int J Med Sci 2018; 15(14): 1713-22.
- Kabagambe EK, Judd SE, Howard VJ, Zakai NA, Jenny NS, Hsieh M, et al. Inflammation biomarkers and risk of all-cause mortality in the Reasons for Geographic and Racial Differences in Stroke Cohort. Am J Epidemiol 2011; 174(3): 284-92.
- Azarpazhooh MR, Etemadi MM, Donnan GA, Mokhber N, Majdi MR, Ghayour-Mobarhan M, et al. Excessive incidence of stroke in Iran: evidence from the Mashhad Stroke Incidence Study (MSIS), a population-based study of stroke in the Middle East. Stroke 2010; 41(1): e3-e10.
- Patgiri D, Pathak MS, Sharma P, Kutum T, Mattack N. Serum hsCRP: A novel marker for prediction of cerebrovascular accidents (Stroke). J Clin Diagn Res
2014; 8(12): CC08-CC11. - Pexman JH, Barber PA, Hill MD, Sevick RJ, Demchuk AM, Hudon ME, et al. Use of the Alberta Stroke Program Early CT Score (ASPECTS) for assessing CT scans in patients with acute stroke. AJNR Am J Neuroradiol 2001; 22(8): 1534-42.
- Amantea D, Tassorelli C, Petrelli F, Certo M, Bezzi P, Micieli G, et al. Understanding the multifaceted role of inflammatory mediators in ischemic stroke. Curr Med Chem 2014; 21(18): 2098-117.
- Domac FM, Somay G, Misirli H, Erenoglu NY. Tumor necrosis factor alpha serum levels andinflammatory response in acute ischemic stroke. Neurosciences (Riyadh) 2007; 12(1):
25-30. - Wytrykowska A, Prosba-Mackiewicz M, Nyka WM. IL-1beta, TNF-alpha, and IL-6 levels in gingival fluid and serum of patients with ischemic stroke. J Oral Sci 2016; 58(4): 509-13.
- Ozkan AK, Yemisci OU, Saracgil Cosar SN, Oztop P, Turhan N. Can high-sensitivity C-reactive protein and ferritin predict functional outcome in acute ischemic stroke? A prospective study. Top Stroke Rehabil 2013; 20(6): 528-36.
- Kulesh AA, Kuklina EM, Shestakov VV. The relationship between serum and liquor IL-1beta, IL-6, TNFalpha, IL-10 levels and clinical, cognitive and functional characteristics in acute ischemic stroke. Klin Med (Mosk) 2016; 94(9): 657-62.
- Mazaheri S, Reisi E, Poorolajal J, Ghiasian M. C-reactive protein levels and clinical outcomes in stroke patients: A prospective cohort study. Arch Iran Med 2018; 21(1): 8-12.
- Fahmi RM, Elsaid AF. Infarction size, interleukin-6, and their interaction are predictors of short-term stroke outcome in young egyptian adults. J Stroke Cerebrovasc Dis 2016; 25(10): 2475-81.
- Rocco A, Ringleb PA, Grittner U, Nolte CH, Schneider A, Nagel S. Follow-up C-reactive protein level is more strongly associated with outcome in stroke patients than admission levels. Neurol Sci 2015; 36(12): 2235-41.
- Banwell V, Sena ES, Macleod MR. Systematic review and stratified meta-analysis of the efficacy of interleukin-1 receptor antagonist in animal models of stroke. J Stroke Cerebrovasc Dis 2009; 18(4): 269-76.
- Drieu A, Levard D, Vivien D, Rubio M. Anti-inflammatory treatments for stroke: from bench to bedside. Ther Adv Neurol Disord 2018; 11: 1756286418789854.
- Smith CJ, Hulme S, Vail A, Heal C, Parry-Jones AR, Scarth S, et al. SCIL-STROKE (Subcutaneous Interleukin-1 Receptor Antagonist in Ischemic Stroke): A Randomized Controlled Phase 2 Trial. Stroke 2018; 49(5): 1210-6.
- Wang X, Xuan W, Zhu ZY, Li Y, Zhu H, Zhu L, et al. The evolving role of neuro-immune interaction in brain repair after cerebral ischemic stroke. CNS Neurosci Ther 2018; 24(12): 1100-14.
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