Outcome following severe traumatic brain injury TBI correlates with serum S100B but not brain extracellular fluid S100B: An intracerebral microdialysis study


S100B protein is released by astrocytes into the brain extracellular fluid following acute brain injury and elevated levels in CSF and serum have been shown to correlate with patient outcome following traumatic brain injury. A prospective study of brain extracellular fluid (ECF) and serum S100B levels in 12 patients with severe head injury (GCS ≤ 8) was undertaken using intracerebral microdialysis to investigate whether a correlation with ECF S100B and outcome could be confirmed. Patient outcomes were assessed at 6 months using the Glasgow Outcome Scale (GOS) and divided into two outcome groups: group A, 8 survivors with either a good recovery or moderate disability (GOS scores of 4 or 5); and group B, 4 patients who died (GOS 1). Peak serum levels of S100B were significantly greater in group B (mean 6.03 ng/ml) compared with group A (mean 0.73 ng/ml) (P = 0.009). Group A had a mean peak S100B in the extracellular compartment of 186 ng/ml compared to 150 ng/ml in group B. There was no significant difference between the mean peak brain ECF S100B concentrations for the 2 outcome groups (P = 0.932). We confirm that intracerebral microdialysis can be used to sample S100B concentrations from brain extracellular fluid and our results suggest that the ECF S100B levels were variable and that there was no significant difference between the good outcome and poor outcome groups. In contrast, the serum levels of S100B of patients with a poor outcome were significantly higher than those with a good outcome.

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Winter, C. , Clough, G. , Pringle, A. and Church, M. (2013) Outcome following severe traumatic brain injury TBI correlates with serum S100B but not brain extracellular fluid S100B: An intracerebral microdialysis study. World Journal of Neuroscience, 3, 93-99. doi: 10.4236/wjns.2013.32013.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Jennett, B. (1996) Epidemiology of head injury. Journal of Neurology, Neurosurgery & Psychiatry, 60, 362-369. doi:10.1136/jnnp.60.4.362
[2] Steyerberg, E.W., Mushkudiani, N., Perel, P., Butcher, I., Lu, J., McHugh, G.S., Murray, G.D., Marmarou, A., Roberts, I., Habbema, J.D. and Maas, A.I. (2008) Predicting outcome after traumatic brain injury: Development and international validation of prognostic scores based on admission characteristics. PLOS Medicine, 5, Article ID: e165; Discussion e165, doi:10.1371/journal.pmed.0050165
[3] Barger, S.W. and Van Eldik, L.J. ()1992 S100 beta stimulates calcium fluxes in glial and neuronal cells. The Journal of Biological Chemistry, 267, 9689-9694.
[4] Beaudeux, J., Dequen, L. and Foglietti, M. (1999) Pathophysiologic aspects of S100 beta protein: A new biological marker of brain pathology. Annales de Biologie Clinique (Paris), 57, 261-272.
[5] Raabe, A., Grolms, C., Keller, M., Dohnert, J., Sorge, O. and Seifert, V. (1998) Correlation of computed tomogramphy findings and serum brain damage markers following severe head injury. Acta Neurochirurgica (Wien), 140, 787-791. doi:10.1007/s007010050180
[6] Nylen, K., Ost, M., Csajbok, L.Z., Nilsson, I., Hall, C., Blennow, K., Nellgard, B. and Rosengren, L. (2008) Serum levels of S100B, S100A and S100BB are all related to outcome after severe traumatic brain injury. Acta Neurochirurgica (Wien), 150, 221-227. Discussion 227. doi:10.1007/s00701-007-1489-2
[7] Rainey, T., Lesko, M., Sacho, R., Lecky, F. and Childs, C. (2009) Predicting outcome after severe traumatic brain injury using the serum S100B biomarker: Results using a single (24h) time-point. Resuscitation, 80, 341-345. doi:10.1016/j.resuscitation.2008.11.021
[8] Winter, C.D., Iannotti, F., Pringle, A.K., Trikkas, C., Clough, G.F. and Church, M.K. (2002) A microdialysis method for the recovery of IL-1beta, IL-6 and nerve growth factor from human brain in vivo. Journal of Neuroscience Methods, 119, 45-50. doi:10.1016/S0165-0270(02)00153-X
[9] Winter, C.D., Pringle, A., Clough, G.F. and Church, M.K. (2004) Raised parenchymal interleukin-6 levels correlate with improved outcome after traumatic brain injury. Brain, 127, 315-320. doi:10.1093/brain/awh039
[10] Alber, B., Hein, R., Garbe, C., Caroli, U. and Luppa, P.B. (2005) Multicenter evaluation of the analytical and clinical performance of the Elecsys S100 immunoassay in patients with malignant melanoma. Clinical Chemistry and Laboratory Medicine, 43, 557-563. doi:10.1515/CCLM.2005.097
[11] Lara, D.R., Gama, C.S., Belmonte-de-Abreu, P., Portela, L.V., Goncalves, C.A., Fonseca, M., Hauck, S. and Souza, D.O. (2001) Increased serum S100B protein in schizophrenia: A study in medication-free patients. Journal of Psychiatric Research, 35, 11-14. doi:10.1016/S0022-3956(01)00003-6
[12] Portela, L.V., Tort, A.B., Schaf, D.V., Ribeiro, L., Nora, D.B., Walz, R., Rotta, L.N., Silva, C.T., Busnello, J.V., Kapczinski, F., Goncalves, C.A. and Souza, D.O. (2002) The serum S100B concentration is age dependent. Clinical Chemistry, 48, 950-952.
[13] Wiesmann, M., Steinmeier, E., Magerkurth, O., Linn, J., Gottmann, D. and Missler, U. (2010) Outcome prediction in traumatic brain injury: Comparison of neurological status, CT findings and blood levels of S100B and GFAP. Acta Neurologica Scandinavica, 121, No. 3, 2010, pp. 178-185. doi:10.1111/j.1600-0404.2009.01196.x
[14] Goyal, A, Carter, M., Niyonkuru, C., Fabio, A., Amin, K., Berger, R.P. and Wagner, A.K. (2012) S100B as a prognostic biomarker in outcome prediction for patients with severe TBI. Journal of Neurotrauma. doi:10.1089/neu.2012.2579
[15] Rodriguez-Rodriguez, A., Egea-Guerrero, J.J., Leon-Justel, A., Cordillo-Escobar, E., Revuelto-Rey, J., Vilches-Arenas, A., Carrillo-Vico, A., Dominguez-Roldan, J.M., Murillo-Cabezas, F. and Guerrero, J.M. (2012) Role of S100B protein in urine and serum as an early predictor of mortality after severe traumatic brain injury in adults. Clinica Chimica Acta, 414, 228-233. doi:10.1016/j.cca.2012.09.025
[16] Bouvier, D., Eisenmann, N., Gillart, T., Bonneau, J., Guelon, D., Schoeffler, P. and Sapin, V. (2012) Jugular venous and arterial concentrations of serum S100B protein in patients with severe head injury. Annales de Biologie Clinique (Paris), 70,269-275.
[17] Thelin, E.P., Johannesson, L.K., Nelson, D.W. and Bellander, B.M. (2013) S100B is an important predictor in traumatic brain injury. Journal of Neurotrauma. doi:10.1089/neu.2012.2553
[18] da Rocha, A.B., Schneider, R.F., de Freitas, G.R., Andre, C., Grivich I., Zanoni, C., Fossa, A., Gehrke, J.T., Pereira, Jotz G., Kaufmann, M., Simon, D. and Regner, A. (2006) Role of serum S100B as a predictive marker of fatal outcome following isolated severe head injury or multitrauma in males. Clinical Chemistry and Laboratory Medicine, 44, 1234-1242. doi:10.1515/CCLM.2006.218
[19] Dimopolou, I., Korfias, S., Dafni, U., Anthi, A., Psachoulia, C., Julien, G., Sakas, D.E. and Roussos, C. (2003) Protein S100B serum levels in trauma-induced brain death. Neurology, 60, 947-951. doi:10.1212/01.WNL.0000049931.77887.7F
[20] Bloomfield, S.M., McKinney, J., Smith, L. and Brisman, J. (2007) Reliability of S100B in predicting severity of central nervous system injury. Neurocritical Care, 6, 121-138. doi:10.1007/s12028-007-0008-x
[21] Mussack, T., Biberthaler, P., Kanz, K.G., Heckl, U., Gruber, R., Linsenmaier, U., Mutscler, W. and Jochum, M. (2002) Immediate S100B and Neuron-Specific Enolase plasma measurements for rapid evaluation of primary brain damage in alcohol-intoxicated, minor head-injured patients. Shock, 18, 395-400. doi:10.1097/00024382-200211000-00002
[22] Anderson, R.E., Hansson, L.O., Nilsson, O., Dijlai-Merzoug, R. and Settergren, G. (2001) High serum S100B levels for trauma patients without head injuries. Neurosurgery, 48, 1255-1258.
[23] Savola, O., Pyhtinen, J., Leino, T.K., Siitonen, S., Niemela, O. and Hillbom, M. (2004) Effects of head and extracranial injuries on serum protein S100B levels in trauma patients. Trauma and Acute Care Surgery, 56, 1229-1234. doi:10.1097/01.TA.0000096644.08735.72
[24] Cotton, B.A., Girard, T.D. and Ely, E.W. (2007) Increased levels of serum S100B protein in critically ill patients without brain injury. Shock, 27, 338. doi:10.1097/01.shk.0000239756.59841.29
[25] Routsi, C., Stamataki, E., Nanas, S., Psachoulia, C., Stathpoulos, A., Koroneos, A., Zervon, M., Julian, G. and Roussos, C. (2006) Increased levels of serum S100B protein in critically ill patients without brain injury. Shock, 26, 20-24. doi:10.1097/01.shk.0000209546.06801.d7
[26] Yardan, T., Erenler, A.K., Baydin, A., Aydin, K. and Cokluk, C. (2011) Usefulness of S100B protein in neurological disorders. Journal of Pakistan Medical Association, 61, 276-281.
[27] Braga, C.W., Martinez, D., Wofchuk, S., Portela, L.V. and Souza, D.O. (2006) S100B and NSE serum levels in obstructive sleep apnea syndrome. Sleep Medicine, 7, 431-435. doi:10.1016/j.sleep.2005.12.012
[28] Mazzini, G.S., Schaf, D.V., Vinade, E.R., Horowitz, E., Bruch, R.S., Brunm, L.M., Goncalves, C.A., Bacal, F., Souza, D.O., Portela, L.V. and Bordignon, S. (2007) Increased S100B serum levels in dilated cardiomyopathy patients. Journal of Cardiac Failure, 13, 850-854. doi:10.1016/j.cardfail.2007.07.009
[29] Yardan, T., Cevik, Y., Donderici, O., Kavalci, C., Yilmaz, F.M., Vural, K., Yuzbasioglu, Y., Gunaydin, Y.K. and Sezer, A.A. (2009) Elevated serum S100B protein and neuron-specific enolase levels in carbon monoxide poisoning. The American Journal of Emergency Medicine, 27, 838-842. doi:10.1016/j.ajem.2008.04.016
[30] Buttner, T., Weyers, S., Postert, T., Sprengelmeyer, R. and Khun, W. (1997) S100 protein: Serum marker of focal brain damage after ischaemic territorial MCA infarction. Stroke, 28, 1961-1965. doi:10.1161/01.STR.28.10.1961
[31] Fassbender, K., Schmidt, R., Schreiner, A., Fatar, M., Muhlhauser, F. and Hennerici, M.D. (1997) Leakage of brain-originated proteins in peripheral blood: Temporal profile and diagnostic value in early ischaemic stroke. Journal of the Neurological Sciences, 148, 101-105. doi:10.1016/S0022-510X(96)05351-8
[32] Herrmann, M., Vos, P., Wunderlich, M.T., de Bruijn, C.H. and Lamers, K.J. (2000) Release of glial tissue-specific protein after acute stroke: A comparative analysis of serum concentrations of protein S100B and glial fibrillary acidic protein. Stroke, 31, 2670-2677. doi:10.1161/01.STR.31.11.2670
[33] Straume-Naesheim, T.M., Anderson, T.E., Jochum, M., Dvorak, J. and Bahr, R. (2008) Minor head trauma in soccer and serum levels of S100B. Neurosurgery, 62, 1297-1305. doi:10.1227/01.neu.0000333301.34189.3d
[34] Otto M., Holthusen S., Bahn E., Sohnchen N., Wiltfang J., Geese R., Fischer A. and Reimers C.D. (2000) Boxing and running lead to a rise in serum levels of S100B protein. International Journal of Sports Medicine, 21, 551-555. doi:10.1055/s-2000-8480
[35] Dietrich M.O., Tort A.B., Schaf, D.V., Farina M., Goncalves C.A., Souza D.O. andPortela L.V. (2003) Increase in serum S100B protein level after a swimming race. Canadian Journal of Applied Physiology, 28, 710-716. doi:10.1139/h03-054
[36] Gonzclez-Mao, M.C., Reparaz-Andrade, A., Del Campo-Perez, V., Alvarez-Garcia, E., Vara-Perez, C. and Andrade-Olivie, M.A. (2011) Model predicting survival/exitus after traumatic brain injury: Biomarker S100B 24h. Clinical Laboratary, 57, 587-597.
[37] Kleindienst, A. and Bullock, R.R. (2006) A critical analysis of the role of the neurotrophic protein S100B in acute brain injury. Journal of Neurotrauma, 23, 1185-1200. doi:10.1089/neu.2006.23.1185
[38] Korn, A., Golan, H., Melamed, I., Pascual-Marqui, R. and Friedman, A. (2005) Focal cortical dysfunction and blood-brain barrier disruption in patients with post-concussion syndrome. Journal of Clinical Neuro-Physiology, 22, 1-9. doi:10.1097/01.WNP.0000150973.24324.A7
[39] Tomkins, O., Shelef, I., Kaizerman, I., Eliushin, A., Misk, Z.A., Gidon, M., Cohen,A., Zumsteg, D. and Friedman, A. (2008) Blood-brain barrier disruption in post-traumatic epilepsy. Journal of Neurosurgery & Psychiatry with Practical Neurology, 79, 774-777. doi:10.1136/jnnp.2007.126425
[40] Shlosberg, D., Benifla, M., Kaufer. D. and Friedman, A. (2010) Blood-brain barrier breakdown as a therapeutic target in traumatic brain injury. Nature Reviews. Neurology, 6, 393-403. doi:10.1038/nrneurol.2010.74
[41] Andersson, M., Alvarez-Cermeno, J., Bernardi, G., Cogato, I., Fredman, P., Frederiksen, J., Fredrikson, S., Gallo, P., Grimaldi, L.M., Gronning, M., Keir, G., Lamers, K., Link, H., Magalhaes, A., Massaro, A.R., Ohman, S., Reiber, H., Ronnback, L., Schluep, M., Schuller, E., Sindic, C.J.M., Thompson, E.J., Trojano, M. and Wurster, U. (1994) Cerebrospinal fluid in the diagnosis of multiple sclerosis: A consensus report. Journal of Neurology, Neurosurgery & Psychiatry with Practical Neurology, 57, 897-902.doi:10.1136/jnnp.57.8.897
[42] Reiber, H. and Peter, J.B. (2001) Cerebrospinal fluid analysis: Disease-related data patterns and evaluation programs. Journal of Neurological Sciences, 184, 101-122.
[43] Blyth, B.J., Farhavar, A., Gee, C., Hawthorn, B., He, H., Nayak, A., Stocklein, V. and Bazarian, J.J. (2009) Validation of serum markers for blood-brain barrier disruption in traumatic brain injury. Journal of Neurotrauma, 26, 1497-1507. doi:10.1089/neu.2008.0738
[44] Bellander, B.M., Olafsson, I.H., Ghatan, P.H., Skejo, B.H.P., Hansson, L.O., Wanecek, M. and Svensson, M.A. (2011) Secondary insults following traumatic brain injury enhance complement activation in the human brain and release of the tissue damage marker S100B. Acta Neurochirurgica, 153, 90-100. doi:10.1007/s00701-010-0737-z
[45] Dayon, L., Turck, N., Garcia-Berrocoso, T., Walter, N., Burkhard, P.R., Vilalta, A., Sahuquillo, J., Montaner, J. and Sanchez, J.C. (2011) Brain extracellular fluid protein changes in acute stroke patients. Journal of Proteome Research, 10, 1043-1051. doi:10.1021/pr101123t
[46] Sen, J., Belli, A., Petzold, A., Russo, S., Keir, G., Thompson, E.J., Smith, M. and Kitchen, N. (2005) Extracellular fluid S100B in the injured brain: A future surrogate marker of acute brain injury? Acta Neurochirurgica, 147, 897-900. doi:10.1007/s00701-005-0526-2
[47] Clough, G.F., Boutsiouki, P., Church, M.K. and Michel, C.C. (2002) Effects of blood flow on the in vivo recovery of a small diffusible molecule by microdialysis in human skin. The Journal of Pharmacology and Experimental Therapeutics, 302, 681-686.doi:10.1124/jpet.102.035634
[48] Cserr, H.F. (1971) Physiology of the choroid plexus. Physiological Reviews, 51, 273-311.
[49] Kirchhoff, C., Buhmann, S., Braunstein, V., Leidel, B.A., Vogel, T., Kreimeier, U., Mutschler, W. and Biberthaler, P. (2008) Cerebrospinal S100-B: A potential marker for progressive intracranial haemorrhage in patients with severe traumatic brain injury. European Journal of Medical Research, 13, 511-516.
[50] Bohmer, A.E., Oses, J.P., Schmidt, A.P., Peron, C.S., Krebs, C.L., Oppitz, P.P., D’Avila, T.T., Souza, D.O., Portela, L.V. and Stefani, M.A. (2011) Neuro-specific enolase, S100B, and glial fibrillary acidic protein levels as outcome predictors in patients with severe traumatic brain injury. Neurosurgery, 68, 1624-1630. doi:10.1227/NEU.0b013e318214a81f
[51] Kliendienst, A., Schmidt, C., Parsch, H., Emtmann, I., Xu, Y. and Buchfelder, M. (2010) The passage of S100B from brain to blood is not specifically related to blood-brain barrier intregrity. Cardiovascular Psychiatry and Neurology, 2010, Article ID: 801295, 8 Pages. doi:10.1155/2010/801295
[52] Stenken, J.A., Church, M.K., Gill, C.A. and Clough, G.F. (2010) How minimally invasive is microdialysis sampling? A cautionary note for cytokine collection in human skin and other clinical studies. AAPS Journals, 12, 73-78. doi:10.1208/s12248-009-9163-7
[53] Benveniste, H. and Diemer, N.H. (1987) Cellular reactions to implantation of a microdialysis tube in the rat hippocampus. Acta Neuropathologica, 74, 234-238. doi:10.1007/BF00688186
[54] Landolt, H., Langemann, H. and Alessandri, B. (1996) A concept for the introduction of cerebral microdialysis in neurointensive care. Acta Neurochirurgica, 67, S31-S36.
[55] Benveniste, H. and Huttemeier, P.C. (1990) Microdialysis—Theory and application. Progress in Neurobiology, 35, 195-215. doi:10.1016/0301-0082(90)90027-E
[56] Lonnroth, P. and Smith, U. (1990) Microdialysis–A novel technique for clinical investigations. Journal of Internal Medicine, 227, 295-300. doi:10.1111/j.1365-2796.1990.tb00163.x

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