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