• Ramona Åstrand
  • Johan Undén
  • Peter Reinstrup
  • Bertil Romner


Traumatic brain injury (TBI) is a significant cause of mortality and morbidity in adults and a leading cause of death in childhood. The diagnostic process includes clinical examination and in more severe cases neuroimaging, such as computed tomography of the head (CT) or magnetic resonance imaging (MRI). Biochemical markers are constantly being used as diagnostic tools for injuries in specific organs, such as troponin for myocardial infarction, creatinine for renal dysfunction and pancreas amylase and lipase for acute pancreatitis. A biomarker detectable in serum, and easily analysed, would be preferable as a complement to clinical assessment after TBI.


Traumatic Brain Injury Acute Pancreatitis Glial Fibrillary Acidic Protein Brain Death Unfavourable Outcome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Bakay RA, Ward AA Jr (1983) Enzymatic changes in serum and cerebrospinal fluid in neurological injury. J Neurosurg 58:27–37PubMedCrossRefGoogle Scholar
  2. Bellander BM, Olafsson IH, Ghatan PH, Bro Skejo HP, Hansson LO, Wanecek M, Svensson MA (2011) Secondary insults following traumatic brain injury enhance complement activation in the human brain and release of the tissue damage marker S100B. Acta Neurochir (Wien) 153:90–100CrossRefGoogle Scholar
  3. Bohmer AE, Oses JP, Schmidt AP, Peron CS, Krebs CL, Oppitz PP, D’Avila TT, Souza DO, Portela LV, Stefani MA (2011) Neuron-specific enolase, S100B, and glial fibrillary acidic protein levels as outcome predictors in patients with severe traumatic brain injury. Neurosurgery 68:1624–1631PubMedCrossRefGoogle Scholar
  4. da Rocha AB, Schneider RF, de Freitas GR, Andre C, Grivicich I, Zanoni C, Fossa A, Gehrke JT, Pereira Jotz G, Kaufmann M, Simon D, Regner A (2006) Role of serum S100B as a predictive marker of fatal outcome following isolated severe head injury or multitrauma in males. Clin Chem Lab Med 44:1234–1242PubMedGoogle Scholar
  5. Dauberschmidt R, Marangos PJ, Zinsmeyer J, Bender V, Klages G, Gross J (1983) Severe head trauma and the changes of concentration of neuron-specific enolase in plasma and in cerebrospinal fluid. Clin Chim Acta 131:165–170PubMedCrossRefGoogle Scholar
  6. Dimopoulou I, Korfias S, Dafni U, Anthi A, Psachoulia C, Jullien G, Sakas DE, Roussos C (2003) Protein S-100b serum levels in trauma-induced brain death. Neurology 60:947–951PubMedCrossRefGoogle Scholar
  7. Donato R (2003) Intracellular and extracellular roles of S100 proteins. Microsc Res Tech 60:540–551PubMedCrossRefGoogle Scholar
  8. Eng LF (1985) Glial fibrillary acidic protein (GFAP): the major protein of glial intermediate filaments in differentiated astrocytes. J Neuroimmunol 8:203–214PubMedCrossRefGoogle Scholar
  9. Eng LF, Ghirnikar RS, Lee YL (2000) Glial fibrillary acidic protein: GFAP-thirty-one years (1969–2000). Neurochem Res 25:1439–1451PubMedCrossRefGoogle Scholar
  10. Gerbitz KD, Summer J, Schumacher I, Arnold H, Kraft A, Mross K (1986) Enolase isoenzymes as tumour markers. J Clin Chem Clin Biochem 24:1009–1016PubMedGoogle Scholar
  11. Guzel A, Er U, Tatli M, Aluclu U, Ozkan U, Duzenli Y, Satici O, Guzel E, Kemaloglu S, Ceviz A, Kaplan A (2008) Serum neuron-specific enolase as a predictor of short-term outcome and its correlation with Glasgow Coma Scale in traumatic brain injury. Neurosurg Rev 31:439–444; discussion 444–435PubMedCrossRefGoogle Scholar
  12. Herrmann M, Vos P, Wunderlich MT, de Bruijn CH, Lamers KJ (2000) Release of glial tissue-specific proteins after acute stroke: a comparative analysis of serum concentrations of protein S-100B and glial fibrillary acidic protein. Stroke 31:2670–2677PubMedCrossRefGoogle Scholar
  13. Ingebrigtsen T, Waterloo K, Jacobsen EA, Langbakk B, Romner B (1999) Traumatic brain damage in minor head injury: relation of serum S-100 protein measurements to magnetic resonance imaging and neurobehavioral outcome. Neurosurgery 45:468–475; discussion 475–466PubMedCrossRefGoogle Scholar
  14. Ishiguro Y, Kato K, Ito T, Nagaya M (1983) Determination of three enolase isozymes and S-100 protein in various tumors in children. Cancer Res 43:6080–6084PubMedGoogle Scholar
  15. Johnsson P, Lundqvist C, Lindgren A, Ferencz I, Alling C, Stahl E (1995) Cerebral complications after cardiac surgery assessed by S-100 and NSE levels in blood. J Cardiothorac Vasc Anesth 9:694–699PubMedCrossRefGoogle Scholar
  16. Johnsson P, Blomquist S, Luhrs C, Malmkvist G, Alling C, Solem JO, Stahl E (2000) Neuron-specific enolase increases in plasma during and immediately after extracorporeal circulation. Ann Thorac Surg 69:750–754PubMedCrossRefGoogle Scholar
  17. Jonsson H, Johnsson P, Hoglund P, Alling C, Blomquist S (2000) Elimination of S100B and renal function after cardiac surgery. J Cardiothorac Vasc Anesth 14:698–701PubMedCrossRefGoogle Scholar
  18. Lumpkins KM, Bochicchio GV, Keledjian K, Simard JM, McCunn M, Scalea T (2008) Glial fibrillary acidic protein is highly correlated with brain injury. J Trauma 65:778–782; discussion 782–774PubMedCrossRefGoogle Scholar
  19. Marangos PJ, Schmechel DE (1987) Neuron specific enolase, a clinically useful marker for neurons and neuroendocrine cells. Annu Rev Neurosci 10:269–295PubMedCrossRefGoogle Scholar
  20. Meric E, Gunduz A, Turedi S, Cakir E, Yandi M (2010) The prognostic value of neuron-specific enolase in head trauma patients. J Emerg Med 38:297–301PubMedCrossRefGoogle Scholar
  21. Missler U, Wiesmann M, Wittmann G, Magerkurth O, Hagenstrom H (1999) Measurement of glial fibrillary acidic protein in human blood: analytical method and preliminary clinical results. Clin Chem 45:138–141PubMedGoogle Scholar
  22. Moritz S, Warnat J, Bele S, Graf BM, Woertgen C (2010) The prognostic value of NSE and S100B from serum and cerebrospinal fluid in patients with spontaneous subarachnoid hemorrhage. J Neurosurg Anesthesiol 22:21–31PubMedCrossRefGoogle Scholar
  23. Mussack T, Biberthaler P, Kanz KG, Wiedemann E, Gippner-Steppert C, Mutschler W, Jochum M (2002) Serum S-100B and interleukin-8 as predictive markers for comparative neurologic outcome analysis of patients after cardiac arrest and severe traumatic brain injury. Crit Care Med 30:2669–2674PubMedCrossRefGoogle Scholar
  24. Naeimi ZS, Weinhofer A, Sarahrudi K, Heinz T, Vecsei V (2006) Predictive value of S-100B protein and neuron specific-enolase as markers of traumatic brain damage in clinical use. Brain Inj 20:463–468PubMedCrossRefGoogle Scholar
  25. Nylen K, Ost M, Csajbok LZ, Nilsson I, Blennow K, Nellgard B, Rosengren L (2006) Increased serum-GFAP in patients with severe traumatic brain injury is related to outcome. J Neurol Sci 240:85–91PubMedCrossRefGoogle Scholar
  26. Nylen K, Ost M, Csajbok LZ, Nilsson I, Hall C, Blennow K, Nellgard B, Rosengren L (2008) Serum levels of S100B, S100A1B and S100BB are all related to outcome after severe traumatic brain injury. Acta Neurochir (Wien) 150:221–227; discussion 227CrossRefGoogle Scholar
  27. Olivecrona M, Rodling-Wahlstrom M, Naredi S, Koskinen LO (2009) S-100B and neuron specific enolase are poor outcome predictors in severe traumatic brain injury treated by an intracranial pressure targeted therapy. J Neurol Neurosurg Psychiatry 80:1241–1247PubMedCrossRefGoogle Scholar
  28. Pelinka LE, Toegel E, Mauritz W, Redl H (2003) Serum S 100 B: a marker of brain damage in traumatic brain injury with and without multiple trauma. Shock 19:195–200PubMedCrossRefGoogle Scholar
  29. Pelinka LE, Kroepfl A, Leixnering M, Buchinger W, Raabe A, Redl H (2004) GFAP versus S100B in serum after traumatic brain injury: relationship to brain damage and outcome. J Neurotrauma 21:1553–1561PubMedCrossRefGoogle Scholar
  30. Petzold A, Green AJ, Keir G, Fairley S, Kitchen N, Smith M, Thompson EJ (2002) Role of serum S100B as an early predictor of high intracranial pressure and mortality in brain injury: a pilot study. Crit Care Med 30:2705–2710PubMedCrossRefGoogle Scholar
  31. Raabe A, Seifert V (1999) Fatal secondary increase in serum S-100B protein after severe head injury. Report of three cases. J Neurosurg 91:875–877PubMedCrossRefGoogle Scholar
  32. Raabe A, Grolms C, Seifert V (1999a) Serum markers of brain damage and outcome prediction in patients after severe head injury. Br J Neurosurg 13:56–59PubMedCrossRefGoogle Scholar
  33. Raabe A, Grolms C, Sorge O, Zimmermann M, Seifert V (1999b) Serum S-100B protein in severe head injury. Neurosurgery 45:477–483PubMedCrossRefGoogle Scholar
  34. Ross SA, Cunningham RT, Johnston CF, Rowlands BJ (1996) Neuron-specific enolase as an aid to outcome prediction in head injury. Br J Neurosurg 10:471–476PubMedCrossRefGoogle Scholar
  35. Unden J, Bellner J, Eneroth M, Alling C, Ingebrigtsen T, Romner B (2005) Raised serum S100B levels after acute bone fractures without cerebral injury. J Trauma 58:59–61PubMedCrossRefGoogle Scholar
  36. Unden J, Astrand R, Waterloo K, Ingebrigtsen T, Bellner J, Reinstrup P, Andsberg G, Romner B (2007) Clinical significance of serum S100B levels in neurointensive care. Neurocrit Care 6:94–99PubMedCrossRefGoogle Scholar
  37. van Geel WJ, de Reus HP, Nijzing H, Verbeek MM, Vos PE, Lamers KJ (2002) Measurement of glial fibrillary acidic protein in blood: an analytical method. Clin Chim Acta 326:151–154PubMedCrossRefGoogle Scholar
  38. Velasco ME, Ghobrial MW, Ross ER (1985) Neuron-specific enolase and neurofilament protein as markers of differentiation in medulloblastoma. Surg Neurol 23:177–182PubMedCrossRefGoogle Scholar
  39. Vos PE, Lamers KJ, Hendriks JC, van Haaren M, Beems T, Zimmerman C, van Geel W, de Reus H, Biert J, Verbeek MM (2004) Glial and neuronal proteins in serum predict outcome after severe traumatic brain injury. Neurology 62:1303–1310PubMedCrossRefGoogle Scholar
  40. Vos PE, Jacobs B, Andriessen TM, Lamers KJ, Borm GF, Beems T, Edwards M, Rosmalen CF, Vissers JL (2010) GFAP and S100B are biomarkers of traumatic brain injury: an observational cohort study. Neurology 75:1786–1793PubMedCrossRefGoogle Scholar
  41. Wiesmann M, Missler U, Gottmann D, Gehring S (1998) Plasma S-100b protein concentration in healthy adults is age- and sex-independent. Clin Chem 44:1056–1058PubMedGoogle Scholar
  42. Wiesmann M, Steinmeier E, Magerkurth O, Linn J, Gottmann D, Missler U (2010) Outcome prediction in traumatic brain injury: comparison of neurological status, CT findings, and blood levels of S100B and GFAP. Acta Neurol Scand 121:178–185PubMedCrossRefGoogle Scholar
  43. Woertgen C, Rothoerl RD, Metz C, Brawanski A (1999) Comparison of clinical, radiologic, and serum marker as prognostic factors after severe head injury. J Trauma 47:1126–1130PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Ramona Åstrand
    • 1
  • Johan Undén
    • 2
  • Peter Reinstrup
    • 3
  • Bertil Romner
    • 1
  1. 1.Department of Neurosurgery, 2092RigshospitaletCopenhagenDenmark
  2. 2.Department of Anesthesia and Intensive CareSkåne University Hospital MalmöMalmöSweden
  3. 3.Department of AnesthesiologySkåne University Hospital LundLundSweden

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