Determination of inflammatory mediator levels in cerebrospinal fluid during the formation of cerebral vasospasm and delayed cerebral ischemia after subarachnoid hemorrhage
DOI:
https://doi.org/10.25305/unj.287723Keywords:
cerebral vasospasm, delayed cerebral ischemia, subarachnoid hemorrhage, IL-6, TNF-α, IL-17, IL-10Abstract
Introduction. Delayed cerebral ischemia (DCI) and cerebral vasospasm (CV) lead to poor outcomes in patients after aneurysmal subarachnoid hemorrhage (aSAH). The pathophysiology of these complications is not fully understood, preventing the adoption of a single definition. Reliable diagnostic tests and effective evidence-based treatment are lacking.
Objective: to determine the relationship between the concentration of interleukin-6 (IL-6), IL-10, IL-17, tumor necrosis factor-α (TNF-α) in cerebrospinal fluid and formation of delayed complications of subarachnoid hemorrhage.
Materials and methods. The study involved 45 patients with aSAH who were treated in Kharkiv Regional Hospital (18 men and 27 women aged 32 to 73 years (mean age ‒ 45.9±8.5 years). The control group consisted of 20 healthy individuals (8 men and 12 women aged from 32 to 73 years (mean age - 59.2±10.6 years). The occurrence of DCI or CV was recorded. The level of IL-6, IL-10, IL-17 and TNF-α in the cerebrospinal fluid (CSF) was measured in all subjects of the study using enzyme-linked immunosorbent assay.
Results. Levels of IL-6, TNF-α, IL-17, and IL-10 in the CSF of patients with aSAH were higher than in control subjects. In patients with CV, the values of IL-6, IL-17 and TNF-α in CSF exceeded those of patients without CV. The concentration of IL-6 and TNF-α was also increased in the cerebrospinal fluid of patients with DCI.
Conclusions. The obtained results indicate that IL-6 and TNF-α in CSF may be early markers for predicting vasospasm and DCI on the 3rd day after subarachnoid hemorrhage before clinical onset. The content of IL-17 correlates with the formation of cerebral vasospasm, but there is no connection between its level in the CSF and DCI. The concentration of IL-10 in the CSF on the 3rd day after aSAH had no prognostic value either for CV or for DCI formation.
References
1. Neifert SN, Chapman EK, Martini ML, Shuman WH, Schupper AJ, Oermann EK, Mocco J, Macdonald RL. Aneurysmal Subarachnoid Hemorrhage: the Last Decade. Transl Stroke Res. 2021 Jun;12(3):428-446. [CrossRef] [PubMed]
2. Macdonald RL, Schweizer TA. Spontaneous subarachnoid haemorrhage. Lancet. 2017 Feb 11;389(10069):655-666. [CrossRef] [PubMed]
3. Inagawa T. Risk Factors for Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage: A Review of the Literature. World Neurosurg. 2016 Jan;85:56-76. [CrossRef] [PubMed]
4. Rosen DS, Macdonald RL. Subarachnoid hemorrhage grading scales: a systematic review. Neurocrit Care. 2005;2(2):110-8. [CrossRef] [PubMed]
5. Neidert MC, Maldaner N, Stienen MN, Roethlisberger M, Zumofen DW, D'Alonzo D, Marbacher S, Maduri R, Hostettler IC, Schatlo B, Schneider MM, Seule MA, Schöni D, Goldberg J, Fung C, Arrighi M, Valsecchi D, Bijlenga P, Schaller K, Bozinov O, Regli L, Burkhardt JK; Swiss SOS study group. The Barrow Neurological Institute Grading Scale as a Predictor for Delayed Cerebral Ischemia and Outcome After Aneurysmal Subarachnoid Hemorrhage: Data From a Nationwide Patient Registry (Swiss SOS). Neurosurgery. 2018 Dec 1;83(6):1286-1293. [CrossRef] [PubMed]
6. Macdonald RL. Delayed neurological deterioration after subarachnoid haemorrhage. Nat Rev Neurol. 2014 Jan;10(1):44-58. [CrossRef] [PubMed]
7. Inagawa T, Yahara K, Ohbayashi N. Risk factors associated with cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Neurol Med Chir (Tokyo). 2014 Jun 17;54(6):465-73. [CrossRef] [PubMed] [PubMed Central]
8. Kaliuzhka V, Tkachenko A, Myasoedov V, Markevych M, Onishchenko A, Babalyan I, Piatykop V. The Prognostic Value of Eryptosis Parameters in the Cerebrospinal Fluid for Cerebral Vasospasm and Delayed Cerebral Ischemia Formation. World Neurosurg. 2023 May;173:e578-e585. [CrossRef] [PubMed]
9. Rasmussen R, Bache S, Stavngaard T, Møller K. Plasma Levels of ІЛ-6, ІЛ-8, ІЛ-10, ICAM-1, VCAM-1, IFNγ, and TNFα are not Associated with Delayed Cerebral Ischemia, Cerebral Vasospasm, or Clinical Outcome in Patients with Subarachnoid Hemorrhage. World Neurosurg. 2019 Aug;128:e1131-e1136. [CrossRef] [PubMed]
10. Ni W, Gu YX, Song DL, Leng B, Li PL, Mao Y. The relationship between ІЛ-6 in CSF and occurrence of vasospasm after subarachnoid hemorrhage. Acta Neurochir Suppl. 2011;110(Pt 1):203-8. [CrossRef] [PubMed]
11. Kao HW, Lee KW, Kuo CL, Huang CS, Tseng WM, Liu CS, Lin CP. Interleukin-6 as a Prognostic Biomarker in Ruptured Intracranial Aneurysms. PLoS One. 2015 Jul 15;10(7):e0132115. [CrossRef] [PubMed] [PubMed Central]
12. Hendryk S, Jarzab B, Josko J. Increase of the IL-1 beta and IL-6 levels in CSF in patients with vasospasm following aneurysmal SAH. Neuro Endocrinol Lett. 2004 Feb-Apr;25(1-2):141-7. [PubMed]
13. Vergouwen MD, Vermeulen M, van Gijn J, Rinkel GJ, Wijdicks EF, Muizelaar JP, Mendelow AD, Juvela S, Yonas H, Terbrugge KG, Macdonald RL, Diringer MN, Broderick JP, Dreier JP, Roos YB. Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke. 2010 Oct;41(10):2391-5. [CrossRef] [PubMed]
14. Timmerman KL, Amonette WE, Markofski MM, Ansinelli HA, Gleason EA, Rasmussen BB, Mossberg KA. Blunted ІЛ-6 and ІЛ-10 response to maximal aerobic exercise in patients with traumatic brain injury. Eur J Appl Physiol. 2015 Jan;115(1):111-8. [CrossRef] [PubMed]
15. Sarrafzadeh A, Schlenk F, Gericke C, Vajkoczy P. Relevance of cerebral interleukin-6 after aneurysmal subarachnoid hemorrhage. Neurocrit Care. 2010 Dec;13(3):339-46. [CrossRef] [PubMed]
16. Chou SH, Feske SK, Atherton J, Konigsberg RG, De Jager PL, Du R, Ogilvy CS, Lo EH, Ning M. Early elevation of serum tumor necrosis factor-α is associated with poor outcome in subarachnoid hemorrhage. J Investig Med. 2012 Oct;60(7):1054-8. [CrossRef] [PubMed] [PubMed Central]
17. Bacigaluppi S, Zona G, Secci F, Spena G, Mavilio N, Brusa G, Agid R, Krings T, Ottonello G, Fontanella M. Diagnosis of cerebral vasospasm and risk of delayed cerebral ischemia related to aneurysmal subarachnoid haemorrhage: an overview of available tools. Neurosurg Rev. 2015 Oct;38(4):603-18. [CrossRef] [PubMed]
18. Schoch B, Regel JP, Wichert M, Gasser T, Volbracht L, Stolke D. Analysis of intrathecal interleukin-6 as a potential predictive factor for vasospasm in subarachnoid hemorrhage. Neurosurgery. 2007 May;60(5):828-36; discussion 828-36. [CrossRef] [PubMed]
19. Croci DM, Sivanrupan S, Wanderer S, Agnoletto GJ, Chiappini A, Grüter BE, Andereggen L, Mariani L, Taussky P, Marbacher S. Preclinical and clinical role of interleukin-6 in the development of delayed cerebral vasospasm and neuronal cell death after subarachnoid hemorrhage: towards a potential target therapy? Neurosurg Rev. 2022 Feb;45(1):395-403. [CrossRef] [PubMed] [PubMed Central]
20. Chaudhry SR, Stoffel-Wagner B, Kinfe TM, Güresir E, Vatter H, Dietrich D, Lamprecht A, Muhammad S. Elevated Systemic ІЛ-6 Levels in Patients with Aneurysmal Subarachnoid Hemorrhage Is an Unspecific Marker for Post-SAH Complications. Int J Mol Sci. 2017 Dec 1;18(12):2580. [CrossRef] [PubMed] [PubMed Central]
21. Hanafy KA, Grobelny B, Fernandez L, Kurtz P, Connolly ES, Mayer SA, Schindler C, Badjatia N. Brain interstitial fluid TNF-alpha after subarachnoid hemorrhage. J Neurol Sci. 2010 Apr 15;291(1-2):69-73. [CrossRef] [PubMed] [PubMed Central]
22. Vecchione C, Frati A, Di Pardo A, Cifelli G, Carnevale D, Gentile MT, Carangi R, Landolfi A, Carullo P, Bettarini U, Antenucci G, Mascio G, Busceti CL, Notte A, Maffei A, Cantore GP, Lembo G. Tumor necrosis factor-alpha mediates hemolysis-induced vasoconstriction and the cerebral vasospasm evoked by subarachnoid hemorrhage. Hypertension. 2009 Jul;54(1):150-6. [CrossRef] [PubMed]
23. Chen J, Liu X, Zhong Y. Interleukin-17A: The Key Cytokine in Neurodegenerative Diseases. Front Aging Neurosci. 2020 Sep 29;12:566922. [CrossRef] [PubMed] [PubMed Central]
24. Chaudhry SR, Güresir E, Vatter H, Kinfe TM, Dietrich D, Lamprecht A, Muhammad S. Aneurysmal subarachnoid hemorrhage lead to systemic upregulation of ІЛ-23/ІЛ-17 inflammatory axis. Cytokine. 2017 Sep;97:96-103. [CrossRef] [PubMed]
25. Garcia JM, Stillings SA, Leclerc JL, Phillips H, Edwards NJ, Robicsek SA, Hoh BL, Blackburn S, Doré S. Role of Interleukin-10 in Acute Brain Injuries. Front Neurol. 2017 Jun 12;8:244. [CrossRef] [PubMed] [PubMed Central]
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 V.Y. Kaliuzhka, V.O. Piatykop, M.A. Markevych, Y.O. Babalian
This work is licensed under a Creative Commons Attribution 4.0 International License.
Ukrainian Neurosurgical Journal abides by the CREATIVE COMMONS copyright rights and permissions for open access journals.
Authors, who are published in this Journal, agree to the following conditions:
1. The authors reserve the right to authorship of the work and pass the first publication right of this work to the Journal under the terms of Creative Commons Attribution License, which allows others to freely distribute the published research with the obligatory reference to the authors of the original work and the first publication of the work in this Journal.
2. The authors have the right to conclude separate supplement agreements that relate to non-exclusive work distribution in the form of which it has been published by the Journal (for example, to upload the work to the online storage of the Journal or publish it as part of a monograph), provided that the reference to the first publication of the work in this Journal is included.
