Interleukin 6 and Aneurysmal Subarachnoid Hemorrhage. A Narrative Review
Abstract
:1. Introduction
2. IL-6 and Neuroinflammation
3. IL-6 and SAH
3.1. Aneurysm Formation and Rupture
3.2. Early Brain Injury
3.3. Delayed Cerebral Ischemia
3.4. EVD Related Infections
3.5. Clinical Outcomes
4. Perspectives
4.1. IL-6 as a Biomarker in SAH Patients?
4.2. Antiinflammatory Therapy
4.3. Preclinical Studies
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- De Rooij, N.K.; Linn, F.H.H.; Van Der Plas, J.A.; Algra, A.; Rinkel, G.J.E. Incidence of subarachnoid haemorrhage: A systematic review with emphasis on region, age, gender and time trends. J. Neurol. Neurosurg. Psychiatry 2007, 78, 1365–1372. [Google Scholar] [CrossRef]
- Rabinstein, A.A.; Lanzino, G. Aneurysmal Subarachnoid Hemorrhage. Neurosurg. Clin. N. Am. 2018, 29, 255–262. [Google Scholar] [CrossRef]
- Vergouwen, M.D.I.; Vermeulen, M.; Van Gijn, J.; Rinkel, G.J.E.; Wijdicks, E.F.; Muizelaar, J.P.; Mendelow, A.D.; Juvela, S.; Yonas, H.; Terbrugge, K.G.; et al. Definition of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage as an Outcome Event in Clinical Trials and Observational Studies. Stroke 2010, 41, 2391–2395. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rass, V.; Helbok, R. How to diagnose delayed cerebral ischaemia and symptomatic vasospasm and prevent cerebral infarction in patients with subarachnoid haemorrhage. Curr. Opin. Crit. Care 2021, 27, 103–114. [Google Scholar] [CrossRef] [PubMed]
- Inagawa, T. Risk Factors for Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage: A Review of the Literature. World Neurosurg. 2016, 85, 56–76. [Google Scholar] [CrossRef] [PubMed]
- Anetsberger, A.; Gempt, J.; Blobner, M.; Ringel, F.; Bogdanski, R.; Heim, M.; Schneider, G.; Meyer, B.; Schmid, S.; Ryang, Y.-M.; et al. Impact of Goal-Directed Therapy on Delayed Ischemia After Aneurysmal Subarachnoid Hemorrhage. Stroke 2020, 51, 2287–2296. [Google Scholar] [CrossRef] [PubMed]
- Yasuno, K.; Bilguvar, K.; Bijlenga, P.; Low, S.-K.; Krischek, B.; Auburger, G.; Simon, M.; Krex, D.; Arlier, Z.; Nayak, N.; et al. Genome-wide association study of intracranial aneurysm identifies three new risk loci. Nat. Genet. 2010, 42, 420–425. [Google Scholar] [CrossRef]
- Yasuno, K.; Bakırcıoğlu, M.; Low, S.-K.; Bilgüvar, K.; Gaál, E.; Ruigrok, Y.M.; Niemelä, M.; Hata, A.; Bijlenga, P.; Kasuya, H.; et al. Common variant near the endothelin receptor type A (EDNRA) gene is associated with intracranial aneurysm risk. Proc. Natl. Acad. Sci. USA 2011, 108, 19707–19712. [Google Scholar] [CrossRef] [Green Version]
- Bakker, M.K.; Stroke, H.A.-I.; Van Der Spek, R.A.A.; Van Rheenen, W.; Morel, S.; Bourcier, R.; Hostettler, I.C.; Alg, V.S.; Van Eijk, K.R.; Koido, M.; et al. Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors. Nat. Genet. 2020, 52, 1303–1313. [Google Scholar] [CrossRef]
- Vergouwen, M.D.I.; Vermeulen, M.; Coert, B.A.; Stroes, E.S.G.; Roos, Y.B.W.E.M. Microthrombosis after Aneurysmal Subarachnoid Hemorrhage: An Additional Explanation for Delayed Cerebral Ischemia. Br. J. Pharmacol. 2008, 28, 1761–1770. [Google Scholar] [CrossRef]
- Romano, M.J.G.; Forteza, M.A.M.; Concha, M.M.; Koch, M.S.; Heros, M.R.C.; Morcos, M.J.J.; Babikian, M.V.L. Detection of Microemboli by Transcranial Doppler Ultrasonography in Aneurysmal Subarachnoid Hemorrhage. Neurosurgery 2002, 50, 1026–1031. [Google Scholar] [CrossRef]
- Dreier, J.P.; Woitzik, J.; Fabricius, M.; Bhatia, R.; Major, S.; Drenckhahn, C.; Lehmann, T.-N.; Sarrafzadeh, A.; Willumsen, L.; Hartings, J.A.; et al. Delayed ischaemic neurological deficits after subarachnoid haemorrhage are associated with clusters of spreading depolarizations. Brain 2006, 129, 3224–3237. [Google Scholar] [CrossRef] [PubMed]
- Lucke-Wold, B.P.; Logsdon, A.F.; Manoranjan, B.; Turner, R.C.; McConnell, E.; Vates, G.E.; Huber, J.D.; Rosen, C.L.; Simard, J.M. Aneurysmal Subarachnoid Hemorrhage and Neuroinflammation: A Comprehensive Review. Int. J. Mol. Sci. 2016, 17, 497. [Google Scholar] [CrossRef] [PubMed]
- Rothaug, M.; Becker-Pauly, C.; Rose-John, S. The role of interleukin-6 signaling in nervous tissue. Biochim. Biophys. Acta BBA Bioenerg. 2016, 1863, 1218–1227. [Google Scholar] [CrossRef] [PubMed]
- Disabato, D.J.; Quan, N.; Godbout, J.P. Neuroinflammation: The devil is in the details. J. Neurochem. 2016, 139, 136–153. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mathiesen, T.; Andersson, B.; Loftenius, A.; Von Holst, H. Increased interleukin-6 levels in cerebrospinal fluid following subarachnoid hemorrhage. J. Neurosurg. 1993, 78, 562–567. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yong, H.Y.F.; Rawji, K.S.; Ghorbani, S.; Xue, M.; Yong, V.W. The benefits of neuroinflammation for the repair of the injured central nervous system. Cell. Mol. Immunol. 2019, 16, 540–546. [Google Scholar] [CrossRef]
- Chalouhi, N.; Ali, M.S.; Jabbour, P.M.; Tjoumakaris, S.I.; Gonzalez, L.F.; Rosenwasser, R.H.; Koch, W.J.; Dumont, A.S. Biology of Intracranial Aneurysms: Role of Inflammation. Br. J. Pharmacol. 2012, 32, 1659–1676. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shimada, K.; Furukawa, H.; Wada, K.; Korai, M.; Wei, Y.; Tada, Y.; Kuwabara, A.; Shikata, F.; Kitazato, K.T.; Nagahiro, S.; et al. Protective Role of Peroxisome Proliferator–Activated Receptor-γ in the Development of Intracranial Aneurysm Rupture. Stroke 2015, 46, 1664–1672. [Google Scholar] [CrossRef] [Green Version]
- Wajima, D.; Hourani, S.; Dodd, W.; Patel, D.; Jones, C.; Motwani, K.; Fazal, H.Z.; Hosaka, K.; Hoh, B.L. Interleukin-6 Promotes Murine Estrogen Deficiency-Associated Cerebral Aneurysm Rupture. Neurosurgery 2019, 86, 583–592. [Google Scholar] [CrossRef] [PubMed]
- Chen, Z.; Song, S.; Zhu, J.; Lai, X. Regulatory mechanism of MiR-21 in formation and rupture of intracranial aneurysm through JNK signaling pathway-mediated inflammatory response. Int. J. Clin. Exp. Pathol. 2020, 13, 1834–1841. [Google Scholar] [PubMed]
- Yagi, K.; Kitazato, K.T.; Uno, M.; Tada, Y.; Kinouchi, T.; Shimada, K.; Nagahiro, S. Edaravone, a Free Radical Scavenger, Inhibits MMP-9–Related Brain Hemorrhage in Rats Treated with Tissue Plasminogen Activator. Stroke 2009, 40, 626–631. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ikedo, T.; Minami, M.; Kataoka, H.; Hayashi, K.; Nagata, M.; Fujikawa, R.; Higuchi, S.; Yasui, M.; Aoki, T.; Fukuda, M.; et al. Dipeptidyl Peptidase-4 Inhibitor Anagliptin Prevents Intracranial Aneurysm Growth by Suppressing Macrophage Infiltration and Activation. J. Am. Heart Assoc. 2017, 6. [Google Scholar] [CrossRef]
- Gao, Y.; Zhao, C.; Wang, J.; Li, H.; Yang, B. The potential biomarkers for the formation and development of intracranial aneurysm. J. Clin. Neurosci. 2020, 81, 270–278. [Google Scholar] [CrossRef]
- Sawyer, D.M.; Pace, L.A.; Pascale, C.L.; Kutchin, A.C.; O’Neill, B.E.; Starke, R.M.; Dumont, A.S. Lymphocytes influence intracranial aneurysm formation and rupture: Role of extracellular matrix remodeling and phenotypic modulation of vascular smooth muscle cells. J. Neuroinflamm. 2016, 13, 1–9. [Google Scholar] [CrossRef] [Green Version]
- Hosaka, K.; Rojas, K.; Fazal, H.Z.; Schneider, M.B.; Shores, J.; Federico, V.; Mccord, M.; Lin, L.; Hoh, B. Monocyte Chemotactic Protein-1-Interleukin-6-Osteopontin Pathway of Intra-Aneurysmal Tissue Healing. Stroke 2017, 48, 1052–1060. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Morgan, L. The interleukin-6 gene -174G>C and -572G>C promoter polymorphisms are related to cerebral aneurysms. J. Neurol. Neurosurg. Psychiatry 2006, 77, 915–917. [Google Scholar] [CrossRef] [Green Version]
- Zhang, G.; Tu, Y.; Feng, W.; Huang, L.; Li, M.; Qi, S. Association of interleukin-6-572G/C gene polymorphisms in the Cantonese population with intracranial aneurysms. J. Neurol. Sci. 2011, 306, 94–97. [Google Scholar] [CrossRef] [PubMed]
- McColgan, P.; Thant, K.Z.; Sharma, P. The genetics of sporadic ruptured and unruptured intracranial aneurysms: A genetic meta-analysis of 8 genes and 13 polymorphisms in approximately 20,000 individuals. J. Neurosurg. 2010, 112, 714–721. [Google Scholar] [CrossRef] [PubMed]
- Savarraj, J.; Parsha, K.; Hergenroeder, G.; Ahn, S.; Chang, T.R.; Kim, D.H.; Choi, H.A. Early Brain Injury Associated with Systemic Inflammation After Subarachnoid Hemorrhage. Neurocrit. Care 2017, 28, 203–211. [Google Scholar] [CrossRef]
- Weiying, Z.; Zhiyong, Z.; Peng, Z.; Jie, S.; Xueen, L.; Donghai, W.; Gang, L.; Wandong, S. The impact of initial systemic inflammatory response after aneurysmal subarachnoid hemorrhage. Turk. Neurosurg. 2015, 27, 346–352. [Google Scholar] [CrossRef] [Green Version]
- Ďuriš, K.; Neuman, E.; Vybíhal, V.; Juráň, V.; Gottwaldová, J.; Kýr, M.; Vašků, A.; Smrčka, M. Early Dynamics of Interleukin-6 in Cerebrospinal Fluid after Aneurysmal Subarachnoid Hemorrhage. J. Neurol. Surg. Part A Cent. Eur. Neurosurg. 2017, 79, 145–151. [Google Scholar] [CrossRef] [PubMed]
- Ridwan, S.; Grote, A.; Simon, M. Interleukin 6 in cerebrospinal fluid is a biomarker for delayed cerebral ischemia (DCI) related infarctions after aneurysmal subarachnoid hemorrhage. Sci. Rep. 2021, 11, 1–10. [Google Scholar] [CrossRef] [PubMed]
- Mellergård, P.; Åneman, O.; Sjogren, F.; Säberg, C.; Hillman, J. Differences in Cerebral Extracellular Response of Interleukin-1β, Interleukin-6, and Interleukin-10 After Subarachnoid Hemorrhage or Severe Head Trauma in Humans. Neurosurgery 2011, 68, 12–19. [Google Scholar] [CrossRef]
- Gaetani, P.; Tartara, F.; Pignattit, P.; Tancioni, F.; Rodriguez, R.; Baena, B.; De Benedettit, F. Cisternal CSF levels of cytokines after subarachnoid hemorrhage. Neurol. Res. 1998, 20, 337–342. [Google Scholar] [CrossRef] [PubMed]
- Gruber, A.; Rössler, K.; Graninger, W.; Donner, A.; Illievich, U.M.; Czech, T. Ventricular Cerebrospinal Fluid and Serum Concentrations of sTNFR-I, IL-1ra, and IL-6 After Aneurysmal Subarachnoid Hemorrhage. J. Neurosurg. Anesthesiol. 2000, 12, 297–306. [Google Scholar] [CrossRef] [PubMed]
- Fassbender, K.; Hodapp, B.; Rossol, S.; Bertsch, T.; Schmeck, J.; Schütt, S.; Fritzinger, M.; Horn, P.; Vajkoczy, P.; Kreisel, S.; et al. Inflammatory cytokines in subarachnoid haemorrhage: Association with abnormal blood flow velocities in basal cerebral arteries. J. Neurol. Neurosurg. Psychiatry 2001, 70, 534–537. [Google Scholar] [CrossRef]
- Kwon, K.Y.; Jeon, B.C. Cytokine Levels in Cerebrospinal Fluid and Delayed Ischemic Deficits in Patients with Aneurysmal Subarachnoid Hemorrhage. J. Korean Med. Sci. 2001, 16, 774–780. [Google Scholar] [CrossRef] [Green Version]
- Schoch, B.; Regel, J.P.; 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, 60, 828–836. [Google Scholar] [CrossRef]
- Nakahara, T.; Tsuruta, R.; Kaneko, T.; Yamashita, S.; Fujita, M.; Kasaoka, S.; Hashiguchi, T.; Suzuki, M.; Maruyama, I.; Maekawa, T. High-Mobility Group Box 1 Protein in CSF of Patients with Subarachnoid Hemorrhage. Neurocrit. Care 2009, 11, 362–368. [Google Scholar] [CrossRef]
- Sarrafzadeh, A.; Schlenk, F.; Gericke, C.; Vajkoczy, P. Relevance of Cerebral Interleukin-6 After Aneurysmal Subarachnoid Hemorrhage. Neurocrit. Care 2010, 13, 339–346. [Google Scholar] [CrossRef] [PubMed]
- Muroi, C.; Bellut, D.; Coluccia, D.; Mink, S.; Fujioka, M.; Keller, E. Systemic interleukin-6 concentrations in patients with perimesencephalic non-aneurysmal subarachnoid hemorrhage. J. Clin. Neurosci. 2011, 18, 1626–1629. [Google Scholar] [CrossRef] [Green Version]
- Ni, W.; Ni, W.; Gu, Y.X.; Gu, Y.X.; Song, D.L.; Song, D.L.; Leng, B.; Leng, B.; Li, P.L.; Li, P.L.; et al. The Relationship Between IL-6 in CSF and Occurrence of Vasospasm After Subarachnoid Hemorrhage. In Proceedings of the Early Brain Injury or Cerebral Vasospasm; Springer: Berlin/Heidelberg, Germany, 2011; Volume 110, pp. 203–208. [Google Scholar]
- Chou, S.H.-Y.; Feske, S.K.; Atherton, J.; Konigsberg, R.G.; De Jager, P.L.; Du, R.; Ogilvy, C.S.; Lo, E.H.; Ning, M. Early Elevation of Serum Tumor Necrosis Factor-α Is Associated With Poor Outcome in Subarachnoid Hemorrhage. J. Investig. Med. 2012, 60, 1054–1058. [Google Scholar] [CrossRef] [PubMed]
- McMahon, C.J.; Hopkins, S.; Vail, A.; King, A.T.; Smith, D.; Illingworth, K.J.; Clark, S.; Rothwell, N.J.; Tyrrell, P.J. Inflammation as a predictor for delayed cerebral ischemia after aneurysmal subarachnoid haemorrhage. J. Neurointerv. Surg. 2012, 5, 512–517. [Google Scholar] [CrossRef] [Green Version]
- Muroi, C.; Hugelshofer, M.; Seule, M.; Tastan, I.; Fujioka, M.; Mishima, K.; Keller, E. Correlation Among Systemic Inflammatory Parameter, Occurrence of Delayed Neurological Deficits, and Outcome After Aneurysmal Subarachnoid Hemorrhage. Neurosurgery 2012, 72, 367–375. [Google Scholar] [CrossRef] [PubMed]
- Höllig, A.; Remmel, D.; Stoffel-Wagner, B.; Schubert, G.A.; Coburn, M.; Clusmann, H. Association of early inflammatory parameters after subarachnoid hemorrhage with functional outcome: A prospective cohort study. Clin. Neurol. Neurosurg. 2015, 138, 177–183. [Google Scholar] [CrossRef]
- Höllig, A.; Thiel, M.; Stoffel-Wagner, B.; Coburn, M.; Clusmann, H. Neuroprotective properties of dehydroepiandrosterone-sulfate and its relationship to interleukin 6 after aneurysmal subarachnoid hemorrhage: A prospective cohort study. Crit. Care 2015, 19, 1–9. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kao, H.-W.; Lee, K.-W.; Kuo, C.-L.; Huang, C.-S.; Tseng, W.-M.; Liu, C.-S.; Lin, C.-P. Interleukin-6 as a Prognostic Biomarker in Ruptured Intracranial Aneurysms. PLoS ONE 2015, 10, e0132115. [Google Scholar] [CrossRef]
- Tang, Q.-F.; Lu, S.-Q.; Zhao, Y.-M.; Qian, J.-X. The changes of von willebrand factor/a disintegrin-like and metalloprotease with thrombospondin type I repeats-13 balance in aneurysmal subarachnoid hemorrhage. Int. J. Clin. Exp. Med. 2015, 8, 1342–1348. [Google Scholar] [PubMed]
- Wu, W.; Guan, Y.; Zhao, G.; Fu, X.-J.; Guo, T.-Z.; Liu, Y.-T.; Ren, X.-L.; Wang, W.; Liu, H.-R.; Li, Y.-Q. Elevated IL-6 and TNF-α Levels in Cerebrospinal Fluid of Subarachnoid Hemorrhage Patients. Mol. Neurobiol. 2016, 53, 3277–3285. [Google Scholar] [CrossRef]
- Chamling, B.; Gross, S.; Stoffel-Wagner, B.; Schubert, G.A.; Clusmann, H.; Coburn, M.; Höllig, A. Early Diagnosis of Delayed Cerebral Ischemia: Possible Relevance for Inflammatory Biomarkers in Routine Clinical Practice? World Neurosurg. 2017, 104, 152–157. [Google Scholar] [CrossRef]
- Chaudhry, S.R.; Stoffel-Wagner, B.; Kinfe, T.M.; Güresir, E.; Vatter, H.; Dietrich, D.; Lamprecht, A.; Muhammad, S. Elevated Systemic IL-6 Levels in Patients with Aneurysmal Subarachnoid Hemorrhage Is an Unspecific Marker for Post-SAH Complications. Int. J. Mol. Sci. 2017, 18, 2580. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kiiski, H.; Långsjö, J.; Tenhunen, J.; Ala-Peijari, M.; Huhtala, H.; Hämäläinen, M.; Moilanen, E.; Öhman, J.; Peltola, J. Time-courses of plasma IL-6 and HMGB-1 reflect initial severity of clinical presentation but do not predict poor neurologic outcome following subarachnoid hemorrhage. eNeurologicalSci 2017, 6, 55–62. [Google Scholar] [CrossRef] [PubMed]
- Lenski, M.; Huge, V.; Briegel, J.; Tonn, J.-C.; Schichor, C.; Thon, N. Interleukin 6 in the Cerebrospinal Fluid as a Biomarker for Onset of Vasospasm and Ventriculitis After Severe Subarachnoid Hemorrhage. World Neurosurg. 2017, 99, 132–139. [Google Scholar] [CrossRef]
- Wang, L.; Gao, Z. Expression of MMP-9 and IL-6 in patients with subarachnoid hemorrhage and the clinical significance. Exp. Ther. Med. 2017, 15, 1510–1514. [Google Scholar] [CrossRef] [PubMed]
- Vlachogiannis, P.; Hillered, L.; Khalil, F.; Enblad, P.; Ronne-Engström, E. Interleukin-6 Levels in Cerebrospinal Fluid and Plasma in Patients with Severe Spontaneous Subarachnoid Hemorrhage. World Neurosurg. 2019, 122, e612–e618. [Google Scholar] [CrossRef] [PubMed]
- Ahn, S.-H.; Savarraj, J.P.J.; Parsha, K.; Hergenroeder, G.W.; Chang, T.R.; Kim, D.H.; Kitagawa, R.S.; Blackburn, S.L.; Choi, H.A. Inflammation in delayed ischemia and functional outcomes after subarachnoid hemorrhage. J. Neuroinflamm. 2019, 16, 213. [Google Scholar] [CrossRef]
- Al-Tamimi, Y.Z.; Bhargava, D.; Orsi, N.M.; Teraifi, A.; Cummings, M.; Ekbote, U.V.; Quinn, A.C.; Homer-Vanniasinkam, S.; Ross, S. Compartmentalisation of the inflammatory response following aneurysmal subarachnoid haemorrhage. Cytokine 2019, 123, 154778. [Google Scholar] [CrossRef]
- Rasmussen, R.; Bache, S.; Stavngaard, T.; Møller, K. Plasma Levels of IL-6, IL-8, IL-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, 128, e1131–e1136. [Google Scholar] [CrossRef]
- Wenneberg, S.B.; Hergès, H.O.; Svedin, P.; Mallard, C.; Karlsson, T.; Adiels, M.; Naredi, S.; Block, L. Association between inflammatory response and outcome after subarachnoid haemorrhage. Acta Neurol. Scand. 2021, 143, 195–205. [Google Scholar] [CrossRef]
- Frontera, J.A.; Fernandez, A.; Schmidt, J.M.; Claassen, J.; Wartenberg, K.E.; Badjatia, N.; Connolly, E.S.; Mayer, S.A. Defining Vasospasm After Subarachnoid Hemorrhage. Stroke 2009, 40, 1963–1968. [Google Scholar] [CrossRef] [Green Version]
- Ditz, C.; Leppert, J.; Neumann, A.; Krajewski, K.L.; Gliemroth, J.; Tronnier, V.M.; Küchler, J. Cerebral Vasospasm After Spontaneous Subarachnoid Hemorrhage: Angiographic Pattern and Its Impact on the Clinical Course. World Neurosurg. 2020, 138, e913–e921. [Google Scholar] [CrossRef]
- Franco, D.M.; Arevalo-Rodriguez, I.; Figuls, M.R.I.; Oleas, N.G.M.; Nuvials, X.; Zamora, J. Plasma interleukin-6 concentration for the diagnosis of sepsis in critically ill adults. Cochrane Database Syst. Rev. 2019, 4, CD011811. [Google Scholar] [CrossRef]
- García-Hernández, P.; Prieto, B.; Martínez-Morillo, E.; Rodríguez, V.; Alvarez, F.V. Interleukin-6 in cerebrospinal fluid as a biomarker of acute meningitis. Ann. Clin. Biochem. Int. J. Lab. Med. 2016, 53, 155–163. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- López-Cortés, L.F.; Marquez-Arbizu, R.; Jimenez-Jimenez, L.M.; Jimenez-Mejías, E.; Caballero-Granado, F.J.; Rey-Romero, C.; Polaina, M.; Pachón, J. Cerebrospinal fluid tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-8 as diagnostic markers of cerebrospinal fluid infection in neurosurgical patients. Crit. Care Med. 2000, 28, 215–219. [Google Scholar] [CrossRef] [PubMed]
- Hopkins, S.J.; McMahon, C.J.; Singh, N.; Galea, J.; Hoadley, M.; Scarth, S.; Patel, H.; Vail, A.; Hulme, S.; Rothwell, N.J.; et al. Cerebrospinal fluid and plasma cytokines after subarachnoid haemorrhage: CSF interleukin-6 may be an early marker of infection. J. Neuroinflamm. 2012, 9, 1–9. [Google Scholar] [CrossRef]
- Stienen, M.N.; Smoll, N.R.; Weisshaupt, R.; Fandino, J.; Hildebrandt, G.; Studerus-Germann, A.; Schatlo, B. Delayed Cerebral Ischemia Predicts Neurocognitive Impairment Following Aneurysmal Subarachnoid Hemorrhage. World Neurosurg. 2014, 82, e599–e605. [Google Scholar] [CrossRef] [PubMed]
- Wostrack, M.; Reeb, T.; Martin, J.; Kehl, V.; Shiban, E.; Preuss, A.; Ringel, F.; Meyer, B.; Ryang, Y.-M. Shunt-Dependent Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage: The Role of Intrathecal Interleukin-6. Neurocrit. Care 2014, 21, 78–84. [Google Scholar] [CrossRef] [PubMed]
- Lenski, M.; Biczok, A.; Huge, V.; Forbrig, R.; Briegel, J.; Tonn, J.-C.; Thon, N. Role of Cerebrospinal Fluid Markers for Predicting Shunt-Dependent Hydrocephalus in Patients with Subarachnoid Hemorrhage and External Ventricular Drain Placement. World Neurosurg. 2019, 121, e535–e542. [Google Scholar] [CrossRef] [PubMed]
- Takizawa, T.; Tada, T.; Kitazawa, K.; Tanaka, Y.; Hongo, K.; Kameko, M.; Uemura, K.-I. Inflammatory cytokine cascade released by leukocytes in cerebrospinal fluid after subarachnoid hemorrhage. Neurol. Res. 2001, 23, 724–730. [Google Scholar] [CrossRef] [PubMed]
- Lolansen, S.D.; Rostgaard, N.; Oernbo, E.K.; Juhler, M.; Simonsen, A.H.; MacAulay, N. Inflammatory Markers in Cerebrospinal Fluid from Patients with Hydrocephalus: A Systematic Literature Review. Dis. Mark. 2021, 2021, 1–12. [Google Scholar] [CrossRef]
- Konczalla, J.; Kashefiolasl, S.; Brawanski, N.; Lescher, S.; Senft, C.; Platz, J.; Seifert, V. Cerebral vasospasm and delayed cerebral infarctions in 225 patients with non-aneurysmal subarachnoid hemorrhage: The underestimated risk of Fisher 3 blood distribution. J. Neurointerv. Surg. 2016, 8, 1247–1252. [Google Scholar] [CrossRef] [PubMed]
- Ridwan, S.; Zur, B.; Kurscheid, J.; Esche, J.; Kristof, R.; Klingmüller, D.; Boström, A. Hyponatremia After Spontaneous Aneurysmal Subarachnoid Hemorrhage—A Prospective Observational Study. World Neurosurg. 2019, 129, e538–e544. [Google Scholar] [CrossRef]
- Williams, T.A.; Leslie, G.D.; Dobb, G.J.; Roberts, B.; Van Heerden, P.V. Decrease in proven ventriculitis by reducing the frequency of cerebrospinal fluid sampling from extraventricular drains. J. Neurosurg. 2011, 115, 1040–1046. [Google Scholar] [CrossRef] [PubMed]
- Hostettler, I.C.; Muroi, C.; Richter, J.K.; Schmid, J.; Neidert, M.C.; Seule, M.; Boss, O.; Pangalu, A.; Germans, M.R.; Keller, E. Decision tree analysis in subarachnoid hemorrhage: Prediction of outcome parameters during the course of aneurysmal subarachnoid hemorrhage using decision tree analysis. J. Neurosurg. 2018, 129, 1499–1510. [Google Scholar] [CrossRef] [Green Version]
- Chaudhry, S.R.; Güresir, A.; Stoffel-Wagner, B.; Fimmers, R.; Kinfe, T.M.; Dietrich, D.; Lamprecht, A.; Vatter, H.; Güresir, E.; Muhammad, S. Systemic High-Mobility Group Box-1. Crit. Care Med. 2018, 46, e1023–e1028. [Google Scholar] [CrossRef]
- Chou, S.H.-Y.; the Unruptured Intracranial Aneurysms and SAH CDE Project Investigators; Macdonald, R.L.; Keller, E. Biospecimens and Molecular and Cellular Biomarkers in Aneurysmal Subarachnoid Hemorrhage Studies: Common Data Elements and Standard Reporting Recommendations. Neurocrit. Care 2019, 30, 46–59. [Google Scholar] [CrossRef] [PubMed]
- Jabbarli, R.; Pierscianek, D.; Oppong, M.D.; Sato, T.; Dammann, P.; Wrede, K.H.; Kaier, K.; Köhrmann, M.; Forsting, M.; Kleinschnitz, C.; et al. Laboratory biomarkers of delayed cerebral ischemia after subarachnoid hemorrhage: A systematic review. Neurosurg. Rev. 2020, 43, 825–833. [Google Scholar] [CrossRef]
- Czorlich, P.; Sauvigny, T.; Ricklefs, F.; Abboud, T.; Nierhaus, A.; Vettorazzi, E.; Reuter, D.A.; Regelsberger, J.; Westphal, M.; Schmidt, N.O. Impact of dexamethasone in patients with aneurysmal subarachnoid haemorrhage. Eur. J. Neurol. 2017, 24, 645–651. [Google Scholar] [CrossRef] [PubMed]
- Mohney, N.; Williamson, C.A.; Rothman, E.; Ball, R.; Sheehan, K.M.; Pandey, A.S.; Fletcher, J.J.; Jacobs, T.L.; Thompson, B.G.; Rajajee, V. A Propensity Score Analysis of the Impact of Dexamethasone Use on Delayed Cerebral Ischemia and Poor Functional Outcomes After Subarachnoid Hemorrhage. World Neurosurg. 2018, 109, e655–e661. [Google Scholar] [CrossRef] [PubMed]
- Manoel, A.L.D.O.; Macdonald, R.L. Neuroinflammation as a Target for Intervention in Subarachnoid Hemorrhage. Front. Neurol. 2018, 9, 292. [Google Scholar] [CrossRef] [Green Version]
- Miller, M.M.; Dakay, K.; Henninger, N.; Mayasi, Y.; Mahta, A.; Yakhkind, A.; Hannoun, A.; Thompson, B.B.; Wendell, L.C.; Carandang, R. Association of Dexamethasone with Shunt Requirement, Early Disability, and Medical Complications in Aneurysmal Subarachnoid Hemorrhage. Neurocrit. Care 2020, 1–9. [Google Scholar] [CrossRef] [PubMed]
- Roberts, I.; Yates, D.; Sandercock, P.; Farrell, B.; Wasserberg, J.; Lomas, G.; Cottingham, R.; Svoboda, P.; Brayley, N.; Mazairac, G.; et al. Effect of intravenous corticosteroids on death within 14 days in 10 008 adults with clinically significant head injury (MRC CRASH trial): Randomised placebo-controlled trial. Lancet 2004, 364, 1321–1328. [Google Scholar] [CrossRef]
- Mees, S.D.; Bergh, W.M.V.D.; Algra, A.; Rinkel, G.J. Antiplatelet therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst. Rev. 2007, CD006184. [Google Scholar] [CrossRef]
- Muroi, C.; Hugelshofer, M.; Seule, M.; Keller, E. The Impact of Nonsteroidal Anti-inflammatory Drugs on Inflammatory Response After Aneurysmal Subarachnoid Hemorrhage. Neurocrit. Care 2014, 20, 240–246. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nagahama, Y.; Allan, L.; Nakagawa, D.; Zanaty, M.; Starke, R.M.; Chalouhi, N.; Jabbour, P.; Brown, R.D.; Derdeyn, C.P.; Leira, E.C.; et al. Dual antiplatelet therapy in aneurysmal subarachnoid hemorrhage: Association with reduced risk of clinical vasospasm and delayed cerebral ischemia. J. Neurosurg. 2018, 129, 702–710. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Oppong, M.D.; Gembruch, O.; Pierscianek, D.; Köhrmann, M.; Kleinschnitz, C.; Deuschl, C.; Mönninghoff, C.; Kaier, K.; Forsting, M.; Sure, U.; et al. Post-treatment Antiplatelet Therapy Reduces Risk for Delayed Cerebral Ischemia due to Aneurysmal Subarachnoid Hemorrhage. Neurosurgery 2018, 85, 827–833. [Google Scholar] [CrossRef] [PubMed]
- Manno, E.M.; Gress, D.R.; Ogilvy, C.S.; Stone, C.M.; Zervas, N.T. The Safety and Efficacy of Cyclosporine A in the Prevention of Vasospasm in Patients with Fisher Grade 3 Subarachnoid Hemorrhages: A Pilot Study. Neurosurgery 1997, 40, 289–293. [Google Scholar] [CrossRef]
- Ryba, M.; Pastuszko, M.; Dziewięcki, C.; Andrychowski, J.; Bojarski, P.; Barczewska, M. A strategy for analyzing multiple parameters with application to aneurysmal SAH patients all of them clipped but treated with and without cyclosporine. Acta Neurochir. 1993, 122, 194–199. [Google Scholar] [CrossRef]
- Singh, N.; Hopkins, S.J.; Hulme, S.; Galea, J.P.; Hoadley, M.; Vail, A.; Hutchinson, P.J.; Grainger, S.; Rothwell, N.J.; King, A.T.; et al. The effect of intravenous interleukin-1 receptor antagonist on inflammatory mediators in cerebrospinal fluid after subarachnoid haemorrhage: A phase II randomised controlled trial. J. Neuroinflamm. 2014, 11, 1–8. [Google Scholar] [CrossRef] [Green Version]
- Galea, J.; Ogungbenro, K.; Hulme, S.; Patel, H.; Scarth, S.; Hoadley, M.; Illingworth, K.; McMahon, C.J.; Tzerakis, N.; King, A.T.; et al. Reduction of inflammation after administration of interleukin-1 receptor antagonist following aneurysmal subarachnoid hemorrhage: Results of the Subcutaneous Interleukin-1Ra in SAH (SCIL-SAH) study. J. Neurosurg. 2018, 128, 515–523. [Google Scholar] [CrossRef] [Green Version]
- Gris, T.; on behalf of the Canadian Critical Care Translational Biology Group; Laplante, P.; Thebault, P.; Cayrol, R.; Najjar, A.; Joannette-Pilon, B.; Brillant-Marquis, F.; Magro, E.; English, S.W.; et al. Innate immunity activation in the early brain injury period following subarachnoid hemorrhage. J. Neuroinflamm. 2019, 16, 1–16. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, T.; Huang, L.; Peng, J.; Zhang, J.H.; Zhang, H. LJ529 attenuates mast cell-related inflammation via A3R-PKCε-ALDH2 pathway after subarachnoid hemorrhage in rats. Exp. Neurol. 2021, 340, 113686. [Google Scholar] [CrossRef]
- Liu, L.; Zhang, P.; Zhang, Z.; Hu, Q.; He, J.; Liu, H.; Zhao, J.; Liang, Y.; He, Z.; Li, X.; et al. LXA4 ameliorates cerebrovascular endothelial dysfunction by reducing acute inflammation after subarachnoid hemorrhage in rats. Neuroscience 2019, 408, 105–114. [Google Scholar] [CrossRef]
- Blecharz-Lang, K.G.; Wagner, J.; Fries, A.; Nieminen-Kelhä, M.; Rösner, J.; Schneider, U.C.; Vajkoczy, P. Interleukin 6-Mediated Endothelial Barrier Disturbances Can Be Attenuated by Blockade of the IL6 Receptor Expressed in Brain Microvascular Endothelial Cells. Transl. Stroke Res. 2018, 9, 631–642. [Google Scholar] [CrossRef]
- Liu, W.; Li, R.; Yin, J.; Guo, S.; Chen, Y.; Fan, H.; Li, G.; Li, Z.; Li, X.; Zhang, X.; et al. Mesenchymal stem cells alleviate the early brain injury of subarachnoid hemorrhage partly by suppression of Notch1-dependent neuroinflammation: Involvement of Botch. J. Neuroinflamm. 2019, 16, 1–20. [Google Scholar] [CrossRef]
- Zhang, J.; Xu, X.; Zhou, D.; Li, H.; You, W.; Wang, Z.; Chen, G. Possible Role of Raf-1 Kinase in the Development of Cerebral Vasospasm and Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats. Mol. Neurobiol. 2014, 52, 1527–1539. [Google Scholar] [CrossRef] [PubMed]
- Guo, Z.; Hu, Q.; Xu, L.; Guo, Z.-N.; Ou, Y.; He, Y.; Yin, C.; Sun, X.; Tang, J.; Zhang, J.H. Lipoxin A4 Reduces Inflammation Through Formyl Peptide Receptor 2/p38 MAPK Signaling Pathway in Subarachnoid Hemorrhage Rats. Stroke 2016, 47, 490–497. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Peng, Y.; Zhuang, J.; Ying, G.; Zeng, H.; Zhou, H.; Cao, Y.; Chen, H.; Xu, C.; Fu, X.; Xu, H.; et al. Stimulator of IFN genes mediates neuroinflammatory injury by suppressing AMPK signal in experimental subarachnoid hemorrhage. J. Neuroinflamm. 2020, 17, 1–20. [Google Scholar] [CrossRef]
- Luo, Y.; Fang, Y.; Kang, R.; Lenahan, C.; Gamdzyk, M.; Zhang, Z.; Okada, T.; Tang, J.; Chen, S.; Zhang, J.H. Inhibition of EZH2 (Enhancer of Zeste Homolog 2) Attenuates Neuroinflammation via H3k27me3/SOCS3/TRAF6/NF-κB (Trimethylation of Histone 3 Lysine 27/Suppressor of Cytokine Signaling 3/Tumor Necrosis Factor Receptor Family 6/Nuclear Factor-κB) in a Rat Model of Subarachnoid Hemorrhage. Stroke 2020, 51, 3320–3331. [Google Scholar] [CrossRef] [PubMed]
- Peng, Y.; Jin, J.; Fan, L.; Xu, H.; He, P.; Li, J.; Chen, T.; Ruan, W.; Chen, G. Rolipram Attenuates Early Brain Injury Following Experimental Subarachnoid Hemorrhage in Rats: Possibly via Regulating the SIRT1/NF-κB Pathway. Neurochem. Res. 2018, 43, 785–795. [Google Scholar] [CrossRef]
- Xie, Z.; Huang, L.; Enkhjargal, B.; Reis, C.; Wan, W.; Tang, J.; Cheng, Y.; Zhang, J.H. Recombinant Netrin-1 binding UNC5B receptor attenuates neuroinflammation and brain injury via PPARγ/NFκB signaling pathway after subarachnoid hemorrhage in rats. Brain Behav. Immun. 2018, 69, 190–202. [Google Scholar] [CrossRef]
- Chen, T.; Wang, W.; Li, J.-R.; Xu, H.-Z.; Peng, Y.-C.; Fan, L.-F.; Yan, F.; Gu, C.; Wang, L.; Chen, G. PARP inhibition attenuates early brain injury through NF-κB/MMP-9 pathway in a rat model of subarachnoid hemorrhage. Brain Res. 2016, 1644, 32–38. [Google Scholar] [CrossRef]
- Xu, H.; Li, J.; Wang, Z.; Feng, M.; Shen, Y.; Cao, S.; Li, T.; Peng, Y.; Fan, L.; Chen, J.; et al. Methylene blue attenuates neuroinflammation after subarachnoid hemorrhage in rats through the Akt/GSK-3β/MEF2D signaling pathway. Brain Behav. Immun. 2017, 65, 125–139. [Google Scholar] [CrossRef] [PubMed]
- Zuo, Y.; Huang, L.; Enkhjargal, B.; Xu, W.; Umut, O.; Travis, Z.D.; Zhang, G.; Tang, J.; Liu, F.; Zhang, J.H. Activation of retinoid X receptor by bexarotene attenuates neuroinflammation via PPARγ/SIRT6/FoxO3a pathway after subarachnoid hemorrhage in rats. J. Neuroinflamm. 2019, 16, 1–15. [Google Scholar] [CrossRef] [Green Version]
- Wang, Y.; Zhou, S.; Han, Z.; Yin, D.; Luo, Y.; Tian, Y.; Wang, Z.; Zhang, J. Fingolimod administration improves neurological functions of mice with subarachnoid hemorrhage. Neurosci. Lett. 2020, 736, 135250. [Google Scholar] [CrossRef] [PubMed]
- Wu, Q.; Qi, L.; Li, H.; Mao, L.; Yang, M.; Xie, R.; Yang, X.; Wang, J.; Zhang, Z.; Kong, J.; et al. Roflumilast Reduces Cerebral Inflammation in a Rat Model of Experimental Subarachnoid Hemorrhage. Inflammation 2017, 40, 1245–1253. [Google Scholar] [CrossRef] [PubMed]
- Croci, D.M.; Wanderer, S.; Strange, F.; Grüter, B.E.; Sivanrupan, S.; Andereggen, L.; Casoni, D.; Von Gunten, M.; Widmer, H.R.; Di Santo, S.; et al. Tocilizumab Reduces Vasospasms, Neuronal Cell Death, and Microclot Formation in a Rabbit Model of Subarachnoid Hemorrhage. Transl. Stroke Res. 2021, 1–11. [Google Scholar] [CrossRef]
Study | Number of Patients 1 | Timing 2 | Marker | DCI 2,3 | Outcome 2,3,4 |
---|---|---|---|---|---|
Gaetani et al., 1998 [35] | 31 SAH 10 controls | d0; surgery | CSF IL-6 | + (if surgery <72 h) | ND |
CSF IL-8, MCP-1, E-selectin | − | ND | |||
Gruber et al., 2000 [36] | 44 SAH | d0–2, 3–5, 6–8, 9–11, 12–14 | CSF & serum IL-6 | − | - |
CSF & serum sTNFR-1, TNF-α, IL-1β | − | - | |||
Fassbender et al., 2001 [37] | 35 SAH 20 controls | d1, 2, 3, 5, 7, 9, 11 | CSF & serum IL-6 | - (+ for CSF IL-6: TCD findings) | - |
CSF & serum TNF-α, IL-1β | − | - | |||
Kwon et al., 2001 [38] | 19 SAH 12 controls | d0; admission | CSF IL6 | + | ND |
CSF TNF-α, IL-1β | + (CSF IL-1 β) | ND | |||
Schoch et al., 2007 [39] | 64 SAH | daily | CSF IL-6 | + (d4-5) | ND |
Nakahara et al., 2009 [40] | 39 SAH | d3, 7, 14 | CSF IL-6 | ND | + |
CSF IL-8, HMGB-1, TNF-α | ND | + (all markers) | |||
Sarrafzadeh et al., 2010 [41] | 38 SAH | d0, 1 (3x), 2–10 (2x daily); admission | CSF, serum & micro-dialysis IL-6 | + (CSF & micro-dialysis IL-6) | - |
Muroi et al., 2011 [42] | 99 SAH 20 BPH | daily | serum IL-6 | + (statistical trend) | ND |
Ni et al., 2011 [43] | 46 SAH | daily | CSF IL-6 | + (d3) | - |
Chou et al., 2012 [44] | 52 SAH | d0–1, 2–3, 4–5, 6–8, 10–14 | serum IL-6 | − (+ for angiographic vasospasm) | - |
serum TNF-α | − (+ for angiographic vasospasm) | + | |||
McMahon et al., 2013 [45] | 149 SAH | every other day | serum IL-6 | + | ND |
WBC, ESR | + | ND | |||
Muroi et al., 2013 [46] | 138 SAH | daily | serum IL-6 | + (d3–7) | + (d3–7) |
WBC, serum PCT & CRP | − | - | |||
Höllig et al., 2015a [47] | 81 SAH (46 with CSF analyses) | serum: d0, CSF: d1; admission | CFS & serum IL-6 | ND | + (CSF & serum) |
CSF & serum LIF, E-selectin, ICAM-1, MMP-9, serum CRP & WBC | ND | + (CSF & serum LIF) | |||
Höllig et al., 2015b [48] | 53 SAH | d0, 1, 4, 7, 10, 14 | serum IL-6 | ND | + |
serum DHEAS | ND | + | |||
Kao et al., 2015 [49] | 53 SAH | d0; aneurysm coiling | serum (during coiling: aneurysm & peripheral. venous) IL-6 | ND | + |
Tang et al., 2015 [50] | 58 SAH | d1, 4, 9 | serum IL-6 | + (for DCI & angiographic vasospasm) | + |
serum ADAMTS13, vWF, P-selectin | + (ADAMTS13: inverse correlation) | + (ADAMTS13: inverse correlation) | |||
Wu et al., 2016 [51] | 57 SAH 65 controls | d2; admission | CSF IL-6 | + | ND |
CSF TNF-α | + | ND | |||
Chamling et al., 2017 [52] | 89 SAH | d0, 1, 4, 7, 10, 14 | serum IL-6 | + (d0 serum IL-6: inverse correlation) | ND |
serum LIF, E-selectin, ICAM-1, MMP-9, CRP & WBC | + (WBC, CRP, LIF: inverse correlation) | ND | |||
Chaudhry et al., 2017 [53] | 80 SAH | d1, 3, 5, 7, 9, 11, 13 | serum IL-6 | + (for DCI & angiographic vasospasm) | + |
Kiiski et al., 2017 [54] | 47 SAH | 0, 12, 24 h, d1, 2, 3, 4, 5 | serum IL-6 | ND | - |
serum HMGB-1 | ND | - | |||
Lenski et al., 2017 [55] | 63 SAH | daily | CSF & serum IL-6 | + | ND |
serum CRP, & WBC CSF PMN% (% polymorphonuclear cells) | − | ND | |||
Zhong et al., 2017 [31] | 89 SAH 12 controls (surgery for incidental aneurysms) | d0; admission | serum IL-6 | + | + |
serum IL-1 β, IL-2, IL-8, IL-10, CRP, T cell subpopulations | − | + (IL-10) | |||
Ďuriš et al., 2018 [32] | 47 SAH | d1–4 (3x daily) | CSF & serum IL-6 | − | + |
CSF & serum TNF-α, IL-1β | − | - | |||
Wang et al., 2018 [56] | 43 SAH 23 controls | d1, 4, 7, 10 | CSF & serum IL-6 | + | ND |
CSF & serum CRP, S100, NO, MMP-9 | + | ND | |||
Vlachogiannis et al., 2018 [57] | 44 SAH | d1, 4, 10 | CSF & serum IL-6 | − | - |
Ahn et al., 2019 [58] | 60 SAH | d0, 1–2, 3–5, 6–8 | serum IL-6 | − | + (d1–2) |
serum, 40 cytokines | + (d0 IP-10, d1–2 PDGF-ABBB, d1–2 & d3–5 CCL5, d6–8 MIP1α) | + (d6–8 MCP-1) | |||
Al-Tamimi et al., 2019 [59] | 43 SAH (29 with CSF analyses) | d1–3, 5, 7, 9 | CSF & serum IL-6 | − | + (d3 serum IL-6, only univariate) |
CSF & serum IL-1α, IL-1β, IL-4, IL-8, IL-10, IL-15, IL-17, IL-18, MCP-1, VEGF, TNF-α | + (CSF IL-4) | - | |||
Rasmussen et al., 2019 [60] | 90 SAH | d3, 8 | serum IL-6 | - | - |
IL-8, IL-10, ICAM-1, VCAM-1, IFNγ, TNF-α, hs (high sensitivity) CRP | − (+ for hsCRP: angiographic vasospasm) | - | |||
Bjerkne Wenneberg et al., 2021 [61] | 64 SAH | d0, 10; admission | serum IL-6 | − | + (d0) |
serum IL-1Ra, TNF-α, ICAM-1, CRP, WBC, PLT | − | + (d0 serum IL-1Ra, TNF-α, CRP; d0 serum: ICAM-1, WBC, PLT, only univariate; d10 CRP) | |||
Ridwan et al., 2021 [33] | 82 SAH | d4–14 (≥3x), overall ≥6x | CSF & serum IL-6 | − (+ for CSF IL-6: DCI with secondary infarct) | + |
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Simon, M.; Grote, A. Interleukin 6 and Aneurysmal Subarachnoid Hemorrhage. A Narrative Review. Int. J. Mol. Sci. 2021, 22, 4133. https://doi.org/10.3390/ijms22084133
Simon M, Grote A. Interleukin 6 and Aneurysmal Subarachnoid Hemorrhage. A Narrative Review. International Journal of Molecular Sciences. 2021; 22(8):4133. https://doi.org/10.3390/ijms22084133
Chicago/Turabian StyleSimon, Matthias, and Alexander Grote. 2021. "Interleukin 6 and Aneurysmal Subarachnoid Hemorrhage. A Narrative Review" International Journal of Molecular Sciences 22, no. 8: 4133. https://doi.org/10.3390/ijms22084133