Calcium-binding protein, S100b, in the blood as a biochemical marker of the neurological state of men in warzones

Keywords: stress; aminotransferases; bilirubin; creatinine; urea; total protein; glucose


Acute and chronic stress are two of the most challenging issues faced by men situated in warzones. According to the main concept of G. Selye, stress response is the most important link during the adaptation of an organism to environmental factors. However, excessively intense or prolonged exposure to stress creates the threat of sustained homeostasis disorder. At present, the primary indicators in clinical studies are the general biochemical parameters of blood alanine aminotransferase, aspartate aminotransferase, bilirubin, creatine, urea, total protein, and glucose levels. But these indicators are not classical markers for determining the state of the nervous system itself and cannot reflect a patient's mental state. In this regard, we tested for a different biomarker; we made an attempt to determine the neurospecific S100b protein in the blood serum by analyzing the correlation between classical and specific methods for diagnosing the state of the nervous system. For this study, blood was collected from 20 patients aged 25 to 45 years old. Participants were divided into two groups: one group of provisionally healthy men and another group of patients who were admitted to the Department of Neurology of the I. Mechnikov Regional Clinical Hospital after military operations (from the territory of the ATU). The standard test kits of PrAT Reagent Company (Dnipro) were used to assess biochemical indicators in accordance with the given instruction in the supplier’s protocol. The activity of each of alanine aminotransferase, aspartate aminotransferase, direct and total bilirubin content, creatine, urea, total protein levels, and astrocyte-specific protein S100b was examined. The level of alanine aminotransferase in the men from the warzone was 23.9 ± 3.9 μmol/l, compared with the healthy men 31.2 ± 0.7 μmol/l. The level of aspartate aminotransferase in the group of men at the neurological department was similar to that in the healthy group. The content of direct bilirubin in the patients at the neurological department increased by 28.0%, compared with the healthy men. The concentration of creatinine, total protein, urea, and glucose levels did not significantly change, compared with healthy volunteers and were in the range of the standard reference data. The content of astrocyte-specific protein, S100b, in the blood of the patients was 0.011 μg/ml, 36.0% more than in the conditionally healthy men 0.007 μg/ml. Prolonged stress could, therefore, induce profound changes in blood brain barrier and registration of neurospecific protein in the blood of men in warzones. These changes could become chronic if or when these men develop other social and economic problems that can be monitored with the specific marker for S100b.


Baptista, T. S. A., Petersen, L. E., Molina, J. K., de Nardi, T., Wieck, A., do Prado, A., Piovesan, D. M., Keisermann, M., Grassi-Oliveira, R., & Bauer, M. E. (2017). Autoantibodies against myelin sheath and S100β are associated with cognitive dysfunction in patients with rheumatoid arthritis. Clinical Rheumatology, 36(9), 1959–1968.

Brindle, R. C., Whittaker, A. C., Bibbey, A., Carroll, D., & Ginty, A. T. (2017). Exploring the possible mechanisms of blunted cardiac reactivity to acute psychological stress. International Journal of Psychophysiology, 113, 1–7.

Buckner, S. L., Mouser, J. G., Dankel, S. J., Jessee, M. B., Mattocks, K. T., & Loenneke, J. P. (2017). The general adaptation syndrome: Potential misapplications to resistance exercise. Journal of Science and Medicine in Sport, 20(11), 1015–1017.

Carroll, D., Ginty, A. T., Whittaker, A. C., Lovallo, W. R., & de Rooij, S. R. (2017). The behavioural, cognitive, and neural corollaries of blunted cardiovascular and cortisol reactions to acute psychological stress. Neuroscience and Biobehavioral Reviews, 77, 74–86.

Delgado-Moreno, R., Robles-Pérez, J. J., & Clemente-Suárez, V. J. (2017). Combat stress decreases memory of warfighters in action. Journal of Medical Systems, 41(8), 124.

Di Battista, A. P., Moes, K. A., Shiu, M. Y., Hutchison, M. G., Churchill, N., Thomas, S. G., & Rhind, S. G. (2018). High-intensity interval training is associated with alterations in blood biomarkers related to brain injury. Frontiers in Physiology, 9, 1367.

Ferrannini, E., Iervasi, G., Cobb, J., Ndreu, R., & Nannipieri, M. (2017). Insulin resistance and normal thyroid hormone levels: Prospective study and metabolomic analysis. AJP Endocrinology and Metabolism, 312(5), E429–E436.

Fox, A., Helmer, D., Tseng, C. L., McCarron, K., Satcher, S., & Osinubi, O. (2018). Autonomic symptoms in gulf war veterans evaluated at the war related illness and injury study center. Military Мedicine, 2018, 227.

Gianaros, P. J., & Wager, T. D. (2015). Brain-body pathways linking psychological stress and physical health. Current Directions in Psychological Science, 24(4), 313–321.

Ginty, A. T., Kraynak, T. E., Fisher, J. P., & Gianaros, P. J. (2017). Cardiovascular and autonomic reactivity to psychological stress: Neurophysiological substrates and links to cardiovascular disease. Autonomic Neuroscience: Basic and Clinical, 207, 2–9.

Golmohammadi, J., Jahanian-Najafabadi, A., & Aliomrani, M. (2018). Chronic oral arsenic exposure and its correlation with serum S100B concentration. Biological Trace Element Research, 2018, 1–8.

Gonzalez, L. L., Garrie, K., & Turner, M. D. (2018). Type 2 diabetes an autoinflammatory disease driven by metabolic stress. Biochimica et Biophysica Acta Molecular Basis of Disease, 1864(11), 3805–3823.

Haeusler, R. A., Camastra, S., Nannipieri, M., Astiarraga, B., Castro-Perez, J., Xie, D., Wang, L., Chakravarthy, M., & Ferrannini, E. (2016). Increased bile acid synthesis and impaired bile acid transport in human obesity. The Journal of Clinical Endocrinology and Metabolism, 101(5), 1935–1944.




Hayden, K., & van Heyningen, C. (2001). Measurement of total protein is a useful inclusion in liver function test profiles. Clinical Chemistry, 47(4), 793–794.


Jeon, C. Y., Furuya, E. Y., Berman, M. F., & Larson, E. L. (2012). The role of pre-operative and post-operative glucose control in surgical-site infections and mortality. PloS One, 7(9), e45616.

Kabadi, S. V., Stoica, B. A., Zimmer, D. B., Afanador, L., Duffy, K. B., Loane, D. J., & Faden, A. I. (2015). S100b inhibition reduces behavioral and pathologic changes in experimental traumatic brain injury. Journal of Cerebral Blood Flow and Metabolism, 35(12), 2010–2020.

Kirkpatrick, H. A., & Heller, G. M. (2014). Post-traumatic stress disorder: Theory and treatment update. The International Journal of Psychiatry in Medicine, 47(4), 337–346.

Kleindienst, A., & Ross Bullock, M. (2006). A critical analysis of the role of the neurotrophic protein S100B in acute brain injury. Journal of Neurotrauma, 23(8), 1185–1200.

Koh, S. X., & Lee, J. K. (2014). S100B as a marker for brain damage and blood-brain barrier disruption following exercise. Sports Medicine, 44(3), 369–385.

Koh, S. X., & Lee, J. K. (2014). S100B as a marker for brain damage and blood-brain barrier disruption following exercise. Sports Medicine, 44(3), 369–385.

Kornicka, K., Śmieszek, A., Szłapka-Kosarzewska, J., Irwin Houston, J. M., Roecken, M., & Marycz, K. (2018). Characterization of apoptosis, autophagy and oxidative stress in pancreatic islets cells and intestinal epithelial cells isolated from equine metabolic syndrome (EMS) horses. International Journal of Molecular Sciences, 19(10), 3068.

Kraynak, T. E., Marsland, A. L., & Gianaros, P. J. (2018). Neural mechanisms linking emotion with cardiovascular disease. Current Cardiology Reports, 20(12), 128.

Li, R. L., Zhang, Z. Z., Peng, M., Wu, Y., Zhang, J. J., Wang, C. Y., & Wang, Y. L. (2013). Postoperative impairment of cognitive function in old mice: A possible role for neuroinflammation mediated by HMGB1, S100B, and RAGE. Journal of Surgical Research, 185(2), 815–824.

Li, X., Wilder-Smith, C. H., Kan, M. E., Lu, J., Cao, Y., & Wong, R. K. (2014). Combat-training stress in soldiers increases S100B, a marker of increased blood-brain-barrier permeability, and induces immune activation. Neuro Endocrinology Letters, 35(1), 58–63.

Marik, P. E., & Bellomo, R. (2013). Stress hyperglycemia: An essential survival response. Critical Care, 17(2), 305.

Mendes Arent, A., de Souza, L. F., Walz, R., & Dafre, A. L. (2014). Perspectives on molecular biomarkers of oxidative stress and antioxidant strategies in traumatic brain injury. BioMed Research International, 2014, Article ID 723060.

Nano, J., Muka, T., Cepeda, M., Voortman, T., Dhana, K., Brahimaj, A., Dehghan, A., & Franco, O. H. (2016). Association of circulating total bilirubin with the metabolic syndrome and type 2 diabetes: A systematic review and meta-analysis of observational evidence. Diabetes and Metabolism, 42(6), 389–397.

Oda, E., & Aizawa, Y. (2013). Total bilirubin is inversely associated with metabolic syndrome but not a risk factor for metabolic syndrome in Japanese men and women. Acta Diabetologica, 50(3), 417–422.

Oppenheimer, S., & Cechetto, D. (2016). The insular cortex and the regulation of cardiac function. Comprehensive Physiology, 6(2), 1081–1133.

Palmfeldt, J., Henningsen, K., Eriksen, S. A., Müller, H. K., & Wiborg, O. (2016). Protein biomarkers of susceptibility and resilience to stress in a rat model of depression. Molecular and Cellular Neuroscience, 74, 87–95.

Perez de la Hoz, R. A., Swieszkowski, S. P., Cintora, F. M., Aladio, J. M., Papini, C. M., Matsudo, M., & Scazziota, A. S. (2018). Neuroendocrine system regulatory mechanisms: Acute coronary syndrome and stress hyperglycaemia. European Cardiology Review, 13(1), 29–34.

Plummer, M. P., Finnis, M. E., Phillips, L. K., Kar, P., Bihari, S., Biradar, V., Moodie, S., Horowitz, M., Shaw, J. E., & Deane, A. M. (2016). Stress induced hyperglycemia and the subsequent risk of type 2 diabetes in survivors of critical illness. PLoS One, 11(11), e0165923.

Rajkowska, G., & Stockmeier, C. A. (2013). Astrocyte pathology in major depressive disorder: Insights from human postmortem brain tissue. Current Drug Targets, 14(11), 1225–1236.

Rau, C. S., Wu, S. C., Chen, Y. C., Chien, P. C., Hsieh, H. Y., Kuo, P. J., & Hsieh, C. H. (2017). Stress-induced hyperglycemia, but not diabetic hyperglycemia, is associated with higher mortality in patients with isolated moderate and severe traumatic brain injury: Analysis of a propensity score-matched population. International Journal of Environmental Research and Public Health, 14(11), e1340.

Roh, H. T., Cho, S. Y., Yoon, H. G., & So, W. Y. (2017). Effect of exercise intensity on neurotrophic factors and blood-brain barrier permeability induced by oxidative-nitrosative stress in male college students. International Journal of Sport Nutrition and Exercise Metabolism, 27(3), 239–246.

Siddiqui, A., Madhu, S. V., Sharma, S. B., & Desai, N. G. (2015). Endocrine stress responses and risk of type 2 diabetes mellitus. The International Journal on the Stress of Biology, 18(5), 498–506.

Sookoian, S., Castaño, G. O., Scian, R., Fernández Gianotti, T., Dopazo, H., Rohr, C., Gaj, G., San Martino, J., Sevic, I., Flichman, D., & Pirola, C. J. (2016). Serum aminotransferases in nonalcoholic fatty liver disease are a signatore of liver metabolic perturbations at the amino acid and Krebs cycle level. The American Journal of Clinical Nutrition, 103(2), 422–434.

Steele, M., Germain, A., & Campbell, J. S. (2017). Mediation and moderation of the relationship between combat experiences and post-traumatic stress symptoms in active duty military personnel. Military Medicine, 182(5), e1632–e1639.

Tahtacı, M., Algın, O., Karakan, T., Yürekli, Ö. T., Alışık, M., Köseoğlu, H., Metin, M. R., Bolat, A. D., Erel, Ö., & Ersoy, O. (2018). Can pancreatic steatosis affects exocrine functions of pancreas? The Turkish Journal of Gastroenterology, 29(5), 588–594.

Ushakova, G. A., Fomenko, O. Z., & Pierzynowski, S. G. (2011). Changes in the levels of neurospecific proteins and in behavioral phenomena in rats with hepatic encephalopathy. Neurophysiology, 43(3), 235–238.

Wang, K. K., Yang, Z., Zhu, T., Shi, Y., Rubenstein, R., Tyndall, J. A., & Manley, G. T. (2018). An update on diagnostic and prognostic biomarkers for traumatic brain injury. Expert Review of Molecular Diagnostics, 18(2), 165–180.

Woodbury-Fariña, M. A. (2014). The importance of glia in dealing with stress. Psychiatric Clinics of North America, 37(4), 679–705.

Yaribeygi, H., Farrokhi, F. R., Butler, A. E., & Sahebkar, A. (2018). Insulin resistance: Review of the underlying molecular mechanisms. Journal of Cellular Physiology, 2018, e27603.

Zhang, L., Ma, X., Jiang, Z., Zhang, K., Zhang, M., Li, Y., Zhao, X., & Xiong, H. (2015). Liver enzymes and metabolic syndrome: A large-scale case-control study. Oncotarget, 6(29), 26782–26788.

Zhang, X., Mu, Y., Yan, W., Ba, J., & Li, H. (2014). Alanine aminotransferase within reference range is associated with metabolic syndrome in middle-aged and elderly Chinese men and women. International Journal of Environmental Research and Public Health, 11(12), 12767–12776.

Zhang, Y., Rothermundt, M., Peters, M., Wiesmann, M., Hoy, L., Arolt, V., Emrich, H. M., & Dietrich, D. E. (2009). S100B serum levels and word memory processing in remitted major depression as reflected by brain potentials. Neuropsychobiology, 59(3), 172–177.

How to Cite
Muraviova, D. V., Buniatov, M. R., & UshakovаG. A. (2018). Calcium-binding protein, S100b, in the blood as a biochemical marker of the neurological state of men in warzones. Regulatory Mechanisms in Biosystems, 9(4), 529-534.

Most read articles by the same author(s)

Obs.: This plugin requires at least one statistics/report plugin to be enabled. If your statistics plugins provide more than one metric then please also select a main metric on the admin's site settings page and/or on the journal manager's settings pages.