Relationship between YKL-40, neuron-specific enolase, tumor necrosis factor-a, interleukin-6, and clinical assessment scores in traumatic brain injury

Authors

1 Department of Medical Biology, Medical Faculty, Medical University of Plovdiv; Research Division, Molecular and Regenerative Medicine, Research Institute at Medical University of Plovdiv, Plovdiv, Bulgaria

2 Department of Anesthesiology, Emergency and Intensive Care Medicine, Medical Faculty, Medical University of Plovdiv; Clinic of Anaesthesiology and Intensive Care Medicine, University Hospital “St. George”, Plovdiv, Bulgaria

3 Department of Analytical Chemistry and Computer Chemistry, Faculty of Chemistry, University of Plovdiv, Plovdiv, Bulgaria

Abstract

Background and Objectives: The aim of the present study is to determine plasma and cerebrospinal levels of YKL-40, in combination with neuron-specific enolase (NSE), interleukin (IL)-6, tumor necrosis factor (TNF)-α, and the clinical scales such as Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation a III, and MARSHALL classification in traumatic brain injury (TBI). Materials and Methods: This was a prospective study conducted on patient cohort of 27 patients with isolated severe TBI. Cerebrospinal fluid (CSF) and plasma were collected on the 24th and 96th h after trauma. CSF samples were obtained also from forensic autopsies of 29 adult healthy cadavers. Results: The CSF level of YKL-40 in TBI patients was higher compared to controls, while no significant change between CSF NSE levels in patients and controls was found. We determined a strong correlation between YKL-40 and NSE levels and TBI clinical assessment scores. The analysis of the influence of independent prognostic factors on the outcome of TBI patients showed that plasma NSE concentrations are the major independent variable which is associated with the survival of TBI patients. Still, changes in IL-6 and TNF-α levels could not be considered as reliable predictors of mortality. Conclusion: We present data for correlation of YKL-40 and NSE levels with clinical scores for assessment of trauma severity and the outcome of TBI patients. Even though further large-scale investigations are required to clarify and evaluate the clinical significance of both biomarkers, our findings suggest that YKL-40 and NSE might be implicated in the pathogenesis of TBI and could indicate the degree of neuroinflammation and brain damage.

Keywords


1. Jennett B. Epidemiology of head injury. J Neurol Neurosurg Psychiatry 1996;60:362‑9.
2. Peeters W, van den Brande R, Polinder S, Brazinova A, Steyerberg EW, Lingsma F, et al. Epidemiology of traumatic brain injury in Europe. Acta Neurochir (Wien) 2015;157:1683‑96.
3. Morganti‑Kossmann MC, Satgunaseelan L, Bye N, Nguyen P, Kossmann, TK. Role of the inflammatory process in traumatic brain damage. In: Kilpatrick T, Ransohoff RM, Wesselingh SL, editors. Inflammatory Diseases of the Central Nervous System. Cambridge: Cambridge University Press; 2009. p. 185‑200.
4. Nissen JJ, Jones PA, Signorini DF, Murray LS, Teasdale GM, Miller JD. Glasgow head injury outcome prediction program: An independent assessment. J Neurol Neurosurg Psychiatry 1999;67:796‑9.
5. Mushkudiani NI, Hukkelhove CW, HernandezAV, Murray GD, Choi SC, Maas AI, et al. A systematic review finds methodological improvements necessary for prognostic models in determining traumatic brain injury outcomes. J Clin Epidemiol 2008;61:331‑43.
6. Perel P, Edwards P, Wentz R, Roberts I. Systemic review of prognostic models in traumatic brain injury. BMC Med Inform Decis Mak 2006;6:38. [doi: 10.1186/1472‑6947‑6‑38].
7. VosPE, LamersKJ, HendriksJC, van HaarenM, BeemsT, ZimmermanC, et al. Glial and neuronal proteins in serum predict outcome after severe traumatic brain injury. Neurology 2004;62:1303‑10.
8. Herrmann M, Curio N, Jost S, Grubich C, Ebert AD, Fork M, et al. Release of biochemical markers of damage to neuronal and glial brain tissue is associated with short and long term neuropsychological outcome after traumatic brain injury. J Neurol Neurosurg Psychiatry 2001;70:95‑100.
9. Fridriksson T, Kini N, Walsh‑Kelly C, Hennes H. Serum neuron‑specific enolase as a predictor of intracranial lesions in children with head trauma: A pilot study. Acad Emerg Med 2000;7:816‑20.
10. Kazakova MH, Staneva DN, Koev IG, Staikov DG, Mateva N, Timonov PT, et al. Protein and mRNA levels of YKL‑40 in high‑grade glioma. Folia Biol (Praha) 2014;60:261‑7.
11. Väänänen T, Koskinen A, Paukkeri EL, Hämäläinen M, Moilanen T, Moilanen E, et al. YKL‑40 as a novel factor associated with inflammation and catabolic mechanisms in osteoarthritic joints. Mediators Inflamm 2014;2014:215140. [doi: 10.1155/2014/215140].
12. Çiledağ A, Kabalak PA, Çelik G, Demir N, Yüksel C, Köycü G, et al. High serum YKL‑40 level is associated with poor prognosis in patients with lung cancer. Tuberk Toraks 2018;66:273‑79.
13. Shao R. YKL‑40 acts as an angiogenic factor to promote tumor angiogenesis. Front Physiol 2013;4:122.
14. Bonneh‑Barkay D, Zagadailov P, Zou H, Niyonkuru C, Figley M, Starkey A, et al. YKL‑40 expression in traumatic brain injury: An initial analysis. J Neurotrauma 2010;27:1215‑23.
15. Shahim P, Tegner Y, Marklund N, Höglund K, Portelius E, Brody DL, et al. Astroglial activation and altered amyloid metabolism in human repetitive concussion. Neurology 2017;88:1400‑7.
16. Kazakova M, Pavlov G, Dikov D, Simitchiev D, Dichev V, Stefanov C, et al. Protein YKL‑40 in cerebrospinal fluid in traumatic brain injury. Acta morphologica et anthropologica 2018;25:61‑66.
17. Kadhim HJ, Duchateau J, Sébire G. Cytokines and brain injury: Invited review. J Intensive Care Med 2008;23:236‑49.
18. Pinsky MR, VincentJL, Deviere J, Alegre M, Kahn RJ, Dupont E. Serum cytokine levels in human septic shock. Relation to multiple‑system organ failure and mortality. Chest 1993;103:565‑75.
19. Hergenroeder GW, Moore AN, McCoy JP Jr, Samsel L, Ward NH 3rd, Clifton GL, et al. Serum IL‑6: A candidate biomarker for intracranial pressure elevation following isolated traumatic brain injury. J Neuroinflammation 2010;7:19.
20. Baker SP, O’Neill B, Haddon W Jr., Long WB. The injury severity score: A method for describing patients with multiple injuries and evaluating emergency care. J Trauma 1974;14:187‑96.
21. Steyerberg EW, Mushkudiani N, Perel P, Butcher I, Lu J, McHugh GS, et al. Predicting outcome after traumatic brain injury: Development and international validation of prognostic scores based on admission characteristics. PLoS Med 2008;5:e165.
22. Carabias CS, Gomez PA, Panero I, Eiriz C, Castaño‑León AM, Egea J, et al. YKL‑40, SAA1, CRP and PCT are promising biomarkers for intracranial severity assessment of traumatic brain injury: Relationship with Glasgow Coma Scale and CT volumetry. World Neurosurgery 2019;134:e120‑43. [doi: 10.1016/j.wneu.2019.09.143].
23. Bigner SH. Cerebrospinal fluid (CSF) cytology: Current status and diagnostic applications. J Neuropathol Exp Neurol 1992;51:235‑45.
24. Gan ZS, Stein SC, Swanson R, Guan S, Garcia L, Mehta D, et al. Blood biomarkers for traumatic brain injury: A quantitative assessment of diagnostic and prognostic accuracy. Front Neurol 2019;10:446. [doi: 
10.3389/fneur.2019.00446].
25. Thomsen SB, Rathcke CN, Zerahn B, Vestergaard H. Increased levels of the calcification marker matrix Gla Protein and the inflammatory markers YKL‑40 and CRP in patients with type 2 diabetes and ischemic heart disease. Cardiovasc Diabetol 2010;9:86.
26. Jafari‑Nakhjavani MR, Ghorbanihaghjo A, Bagherzadeh‑Nobari B, Malek‑Mahdavi A, Rashtchizadeh N. Serum YKL‑40 levels and disease characteristics in patients with rheumatoid arthritis. Caspian J Intern Med 2019;10:92‑7.
27. Kacira T, Hanimoglu H, Kucur M, Sanus GZ, KafadarAM, Tanriverdi T, et al. Elevated cerebrospinal fluid and serum YKL‑40 levels are not associated with symptomatic vasospasm in patients with aneurysmal subarachnoid haemorrhage. J Clin Neurosci 2008;15:1011‑16.
28. AlawiehA, SabraZ, ZhangZ, KobeissyF, WangKKW. Neuro‑proteomics and neuro‑systems biology in the quest of TBI biomarker discovery. In: Wang KKW, Zhang Z, Kobeissy FH, editors. Biomarkers of Brain Injury and Neurological Disorders. 1st ed. FL: Taylor & Francis Boca Raton; 2014. p. 3‑41.
29. MaierB, Schwerdtfeger K, MautesA, Holanda M, Müller M, SteudelWI, et al. Differential release of interleukines 6, 8, and 10 in cerebrospinal fluid and plasma after traumatic brain injury. Shock 2001;15:421‑6.
30. Nwachuku E, Puccio M, AdeboyeA, Chang F, Kim J, Okonkwo O. Time course of cerebrospinal fluid inflammatory biomarkers and relationship to 6‑month neurologic outcome in adult severe traumatic brain injury. Clin Neurol Neurosurg 2016;149:1‑5.
31. Vinores SA, Herman MM, Rubinstein LJ, Marangos PJ. Electron microscopic localization of neuron‑specific enolase in rat and mouse brain. J Histochem Cytochem 1984;32:1295‑302.
32. Bonner JA. Commentary on “Effectiveness of Radiation Therapy on Non–Small‑Cell Lung Cancer”. Clinical Lung Cancer 2001;2:191‑2.
33. Modaghegh MH, Saremi E, Mohamadian M, Jafarzadeh R. Characteristics of trauma in North East Iran and the prevention strategies. Arch Iran Med 2013;16:576‑9.
34. Ebell MH, Preston PS. The effect of the APACHE II score and selected clinical variables on survival following cardiopulmonary resuscitation. Fam Med 1993;25:191‑6.
35. Menegazzi JJ, Davis EA, Sucov AN, Paris PM. Reliability of the Glasgow Coma Scale when used by emergency physicians and paramedics. J Trauma 1993;34:46‑8.
36. Cho DY, Wang YC. Comparison of the APACHE III, APACHE II and Glasgow Coma Scale in acute head injury for prediction of mortality and functional outcome. Intensive Care Med 1997;23:77‑84.
37. NikA, Sheikh AndalibiMS, EhsaeiMR, ZarifianA, Ghayoor KarimianiE, Bahadoorkhan G. The efficacy of Glasgow Coma Scale (GCS) score and Acute Physiology and Chronic Health Evaluation (APACHE) II for predicting hospital mortality of ICU patients with acute traumatic brain injury. Bull Emerg Trauma 2018;6:141‑5.
38. Majdan M, Brazinova A, Rusnak M, Leitgeb J. Outcome prediction after traumatic brain injury: Comparison of the performance of routinely used severity scores and multivariable prognostic models. J Neurosci Rural Pract 2017;8:20‑9.