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A Systematic Review of Inflammatory Cytokine Changes Following Aneurysmal Subarachnoid Hemorrhage in Animal Models and Humans

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Abstract

Aneurysmal subarachnoid hemorrhage (aSAH) is a severe form of stroke that occurs following rupture of a cerebral aneurysm. Acute inflammation and secondary delayed inflammatory responses, both largely controlled by cytokines, work together to create high mortality and morbidity for this group. The trajectory and time course of cytokine change must be better understood in order to effectively manage unregulated inflammation and improve patient outcomes following aSAH. A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Three different search phrases (“cytokines and subarachnoid hemorrhage,” “cytokine levels and subarachnoid hemorrhage,” and “cytokine measurement and subarachnoid hemorrhage”) were applied across three databases (PubMed, SCOPUS, and the Cochrane Library). Our procedures returned 856 papers. After application of inclusion/exclusion criteria, 95 preclinical animal studies and 41 clinical studies remained. Across studies, 22 different cytokines had been investigated, 5 different tissue types were analyzed, and 3 animal models were utilized. Three main pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) demonstrated reliable increases following aSAH across the included studies. While this is a promising area of research for potential therapeutics, there are gaps in the knowledge base that bar progress for clinical translation of this information. In particular, there is a need for investigations that explore the systemic inflammatory response following injury in a more diverse number of cytokines, the balance of specific pro-/anti- inflammatory cytokines, and how these biomarkers relate to patient outcomes and recovery over time.

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Acknowledgements

The authors would like to acknowledge assistance provided by KayLee Scott Strahan, Assistant Professor/Research & Learning Services Librarian at The University of Tennessee Health Science Center, Health Sciences Library.

Funding

This work was supported by a UTHSC Collaborative Research Network Award to AS.

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Authors and Affiliations

  1. Department of Anatomy and Neurobiology, College of Graduate Health Sciences, University of Tennessee Health Science Center, 920 Madison Ave, Memphis, TN, 38163, USA

    Patrick Devlin & Tauheed Ishrat

  2. Neuroscience Institute, University of Tennessee Health Science Center, 875 Monroe Ave, Memphis, TN, 38163, USA

    Patrick Devlin, Tauheed Ishrat & Ansley Grimes Stanfill

  3. Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN, 38163, USA

    Tauheed Ishrat

  4. Department of Acute and Tertiary Care, College of Nursing, University of Tennessee Health Science Center, 874 Union Ave, Memphis, TN, 38163, USA

    Ansley Grimes Stanfill

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  1. Patrick Devlin
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PD and AS participated in the data collection and quality control. PD, AS, and TI drafted the manuscript. All authors approved the final version of the manuscript.

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Correspondence to Ansley Grimes Stanfill.

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Devlin, P., Ishrat, T. & Stanfill, A.G. A Systematic Review of Inflammatory Cytokine Changes Following Aneurysmal Subarachnoid Hemorrhage in Animal Models and Humans. Transl. Stroke Res. 13, 881–897 (2022). https://doi.org/10.1007/s12975-022-01001-y

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