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Update on protein biomarkers in traumatic brain injury with emphasis on clinical use in adults and pediatrics

  • Review Article
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Abstract

Purpose

This review summarizes protein biomarkers in mild and severe traumatic brain injury in adults and children and presents a strategy for conducting rationally designed clinical studies on biomarkers in head trauma.

Methods

We performed an electronic search of the National Library of Medicine’s MEDLINE and Biomedical Library of University of Pennsylvania database in March 2008 using a search heading of traumatic head injury and protein biomarkers. The search was focused especially on protein degradation products (spectrin breakdown product, c-tau, amyloid-β1–42) in the last 10 years, but recent data on “classical” markers (S-100B, neuron-specific enolase, etc.) were also examined.

Results

We identified 85 articles focusing on clinical use of biomarkers; 58 articles were prospective cohort studies with injury and/or outcome assessment.

Conclusions

We conclude that only S-100B in severe traumatic brain injury has consistently demonstrated the ability to predict injury and outcome in adults. The number of studies with protein degradation products is insufficient especially in the pediatric care. Cohort studies with well-defined end points and further neuroproteomic search for biomarkers in mild injury should be triggered. After critically reviewing the study designs, we found that large homogenous patient populations, consistent injury, and outcome measures prospectively determined cutoff values, and a combined use of different predictors should be considered in future studies.

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References

  1. Abrahamson EE, Ikonomovic MD, Ciallella JR, Hope CE, Paljug WR, Isanski BA, Flood DG, Clark RS, Dekosky ST (2006) Caspase inhibition therapy abolishes brain trauma-induced increases in Abeta peptide: implications for clinical outcome. Exp Neurol 197:437–450

    CAS  PubMed  Google Scholar 

  2. Anderson RE, Hansson LO, Nilsson O, jlai-Merzoug R, Settergren G (2001) High serum S100B levels for trauma patients without head injuries. Neurosurgery 48:1255–1258

    CAS  PubMed  Google Scholar 

  3. Aono M, Bennett ER, Kim KS, Lynch JR, Myers J, Pearlstein RD, Warner DS, Laskowitz DT (2003) Protective effect of apolipoprotein E-mimetic peptides on N-methyl-d-aspartate excitotoxicity in primary rat neuronal–glial cell cultures. Neuroscience 116:437–445

    CAS  PubMed  Google Scholar 

  4. Balestreri M, Czosnyka M, Chatfield DA, Steiner LA, Schmidt EA, Smielewski P, Matta B, Pickard JD (2004) Predictive value of Glasgow Coma Scale after brain trauma: change in trend over the past ten years. J Neurol Neurosurg Psychiatry 75:161–162

    CAS  PubMed  Google Scholar 

  5. Bandyopadhyay S, Hennes H, Gorelick MH, Wells RG, Walsh-Kelly CM (2005) Serum neuron-specific enolase as a predictor of short-term outcome in children with closed traumatic brain injury. Acad Emerg Med 12:732–738

    PubMed  Google Scholar 

  6. Barzo P, Marmarou A, Fatouros P, Corwin F, Dunbar JG (1997) Acute blood–brain barrier changes in experimental closed head injury as measured by MRI and Gd-DTPA. Acta Neurochir Suppl 70:243–246

    CAS  PubMed  Google Scholar 

  7. Baydas G, Nedzvetskii VS, Nerush PA, Kirichenko SV, Yoldas T (2003) Altered expression of NCAM in hippocampus and cortex may underlie memory and learning deficits in rats with streptozotocin-induced diabetes mellitus. Life Sci 73:1907–1916

    CAS  PubMed  Google Scholar 

  8. Bazarian JJ, Beck C, Blyth B, von AN, Hasselblatt M (2006) Impact of creatine kinase correction on the predictive value of S-100B after mild traumatic brain injury. Restor Neurol Neurosci 24:163–172

    CAS  PubMed  Google Scholar 

  9. Beaudeux J, Dequen L, Foglietti M (1999) Pathophysiologic aspects of S-100beta protein: a new biological marker of brain pathology. Ann Biol Clin (Paris) 57:261–272

    CAS  Google Scholar 

  10. Beems T, Simons KS, Van Geel WJ, De Reus HP, Vos PE, Verbeek MM (2003) Serum- and CSF-concentrations of brain specific proteins in hydrocephalus. Acta Neurochir (Wien) 145:37–43

    CAS  Google Scholar 

  11. Beers SR, Berger RP, Adelson PD (2007) Neurocognitive outcome and serum biomarkers in inflicted versus non-inflicted traumatic brain injury in young children. J Neurotrauma 24:97–105

    PubMed  Google Scholar 

  12. Berg J, Tagliaferri F, Servadei F (2005) Cost of trauma in Europe. Eur J Neurol 12(Suppl 1):85–90

    PubMed  Google Scholar 

  13. Berger RP (2006) The use of serum biomarkers to predict outcome after traumatic brain injury in adults and children. J Head Trauma Rehabil 21:315–333

    PubMed  Google Scholar 

  14. Berger RP, Adelson PD, Pierce MC, Dulani T, Cassidy LD, Kochanek PM (2005) Serum neuron-specific enolase, S100B, and myelin basic protein concentrations after inflicted and noninflicted traumatic brain injury in children. J Neurosurg 103:61–68

    PubMed  Google Scholar 

  15. Berger RP, Beers SR, Richichi R, Wiesman D, Adelson PD (2007) Serum biomarker concentrations and outcome after pediatric traumatic brain injury. J Neurotrauma 24:1793–1801

    PubMed  Google Scholar 

  16. Berger RP, Dulani T, Adelson PD, Leventhal JM, Richichi R, Kochanek PM (2006) Identification of inflicted traumatic brain injury in well-appearing infants using serum and cerebrospinal markers: a possible screening tool. Pediatrics 117:325–332

    PubMed  Google Scholar 

  17. Berger RP, Pierce MC, Wisniewski SR, Adelson PD, Clark RS, Ruppel RA, Kochanek PM (2002) Neuron-specific enolase and S100B in cerebrospinal fluid after severe traumatic brain injury in infants and children. Pediatrics 109:E31

    PubMed  Google Scholar 

  18. Berger RP, Pierce MC, Wisniewski SR, Adelson PD, Kochanek PM (2002) Serum S100B concentrations are increased after closed head injury in children: a preliminary study. J Neurotrauma 19:1405–1409

    PubMed  Google Scholar 

  19. Biberthaler P, Linsenmeier U, Pfeifer KJ, Kroetz M, Mussack T, Kanz KG, Hoecherl EF, Jonas F, Marzi I (2006) Serum S-100B concentration provides additional information fot the indication of computed tomography in patients after minor head injury: a prospective multicenter study. Shock 25:446–453

    CAS  PubMed  Google Scholar 

  20. Binder LI, Frankfurter A, Rebhun LI (1985) The distribution of tau in the mammalian central nervous system. J Cell Biol 101:1371–1378

    CAS  PubMed  Google Scholar 

  21. Blasko I, Beer R, Bigl M, Apelt J, Franz G, Rudzki D, Ransmayr G, Kampfl A, Schliebs R (2004) Experimental traumatic brain injury in rats stimulates the expression, production and activity of Alzheimer's disease beta-secretase (BACE-1). J Neural Transm 111:523–536

    CAS  PubMed  Google Scholar 

  22. Blennow K, Hesse C, Fredman P (1994) Cerebrospinal fluid apolipoprotein E is reduced in Alzheimer's disease. Neuroreport 5:2534–2536

    CAS  PubMed  Google Scholar 

  23. Blennow K, Nellgard B (2004) Amyloid beta 1–42 and tau in cerebrospinal fluid after severe traumatic brain injury. Neurology 62:159–160

    PubMed  Google Scholar 

  24. Blomquist S, Johnsson P, Luhrs C, Malmkvist G, Solem JO, Alling C, Stahl E (1997) The appearance of S-100 protein in serum during and immediately after cardiopulmonary bypass surgery: a possible marker for cerebral injury. J Cardiothorac Vasc Anesth 11:699–703

    CAS  PubMed  Google Scholar 

  25. Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons (2007) Guidelines for the management of severe traumatic brain injury. J Neurotrauma 24(Suppl):1–106

    Google Scholar 

  26. Brana C, Benham CD, Sundstrom LE (1999) Calpain activation and inhibition in organotypic rat hippocampal slice cultures deprived of oxygen and glucose. Eur J Neurosci 11:2375–2384

    CAS  PubMed  Google Scholar 

  27. Bruns J Jr, Hauser WA (2003) The epidemiology of traumatic brain injury: a review. Epilepsia 44(Suppl 10):2–10

    PubMed  Google Scholar 

  28. Buee L, Bussiere T, Buee-Scherrer V, Delacourte A, Hof PR (2000) Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Brain Res Rev 33:95–130

    CAS  PubMed  Google Scholar 

  29. Buki A, Farkas O, Doczi T, Povlishock JT (2003) Preinjury administration of the calpain inhibitor MDL-28170 attenuates traumatically induced axonal injury. J Neurotrauma 20:261–268

    CAS  PubMed  Google Scholar 

  30. Buki A, Koizumi H, Povlishock JT (1999) Moderate posttraumatic hypothermia decreases early calpain-mediated proteolysis and concomitant cytoskeletal compromise in traumatic axonal injury. Exp Neurol 159:319–328

    CAS  PubMed  Google Scholar 

  31. Buki A, Okonkwo DO, Povlishock JT (1999) Postinjury cyclosporin A administration limits axonal damage and disconnection in traumatic brain injury. J Neurotrauma 16:511–521

    CAS  PubMed  Google Scholar 

  32. Buki A, Siman R, Trojanowski JQ, Povlishock JT (1999) The role of calpain-mediated spectrin proteolysis in traumatically induced axonal injury. J Neuropathol Exp Neurol 58:365–375

    CAS  PubMed  Google Scholar 

  33. Bulut M, Koksal O, Dogan S, Bolca N, Ozguc H, Korfali E, Ilcol YO, Parklak M (2006) Tau protein as a serum marker of brain damage in mild traumatic brain injury: preliminary results. Adv Ther 23:12–22

    CAS  PubMed  Google Scholar 

  34. Cardali S, Maugeri R (2006) Detection of alpha II-spectrin and breakdown products in humans after severe traumatic brain injury. J Neurosurg Sci 50:25–31

    CAS  PubMed  Google Scholar 

  35. Carty H, Pierce A (2002) Non-accidental injury: a retrospective analysis of a large cohort. Eur Radiol 12:2919–2925

    PubMed  Google Scholar 

  36. Chen XH, Siman R, Iwata A, Meaney DF, Trojanowski JQ, Smith DH (2004) Long-term accumulation of amyloid-beta, beta-secretase, presenilin-1, and caspase-3 in damaged axons following brain trauma. Am J Pathol 165:357–371

    CAS  PubMed  Google Scholar 

  37. da Rocha AB, Schneider RF, de Freitas GR, Andre C, Grivicich I, Zanoni C, Fossa A, Gehrke JT, Pereira JG (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 44:1234–1242

    PubMed  Google Scholar 

  38. de Boussard CN, Lundin A, Karlstedt D, Edman G, Bartfai A, Borg J (2005) S100 and cognitive impairment after mild traumatic brain injury. J Rehabil Med 37:53–57

    PubMed  Google Scholar 

  39. De Kruijk Jr, Leffers P, Menheere PP, Meerhoff S, Twijnstra A (2001) S-100B and neuron-specific enolase in serum of mild traumatic brain injury patients. A comparison with health controls. Acta Neurol Scand 103:175–179

    PubMed  Google Scholar 

  40. De Nygren BC, Fredman P, Lundin A, Andersson K, Edman G, Borg J (2004) S100 in mild traumatic brain injury. Brain Inj 18:671–683

    Google Scholar 

  41. Dekosky ST, Abrahamson EE, Ciallella JR, Paljug WR, Wisniewski SR, Clark RS, Ikonomovic MD (2007) Association of increased cortical soluble abeta42 levels with diffuse plaques after severe brain injury in humans. Arch Neurol 64:541–544

    PubMed  Google Scholar 

  42. Diakowski W, Sikorski AF (1995) Interaction of brain spectrin (fodrin) with phospholipids. Biochemistry 34:13252–13258

    CAS  PubMed  Google Scholar 

  43. Duhaime AC, Partington MD (2002) Overview and clinical presentation of inflicted head injury in infants. Neurosurg Clin N Am 13:149–154

    PubMed  Google Scholar 

  44. Emmerling MR, Morganti-Kossmann MC, Kossmann T, Stahel PF, Watson MD, Evans LM, Mehta PD, Spiegel K, Kuo YM (2000) Traumatic brain injury elevates the Alzheimer's amyloid peptide A beta 42 in human CSF. A possible role for nerve cell injury. Ann N Y Acad Sci 903:118–122

    CAS  PubMed  Google Scholar 

  45. Ergun R, Bostanci U, Akdemir G, Beskonakli E, Kaptanoglu E, Gursoy F, Taskin Y (1998) Prognostic value of serum neuron-specific enolase levels after head injury. Neurol Res 20:418–420

    CAS  PubMed  Google Scholar 

  46. Fagan AM, Younkin LH, Morris JC, Fryer JD, Cole TG, Younkin SG, Holtzman DM (2000) Differences in the Abeta40/Abeta42 ratio associated with cerebrospinal fluid lipoproteins as a function of apolipoprotein E genotype. Ann Neurol 48:201–210

    CAS  PubMed  Google Scholar 

  47. Fano G, Biocca S, Fulle S, Mariggio MA, Belia S, Calissano P (1995) The S-100: a protein family in search of a function. Prog Neurobiol 46:71–82

    CAS  PubMed  Google Scholar 

  48. Farkas O, Polgar B, Szekeres-Bartho J, Doczi T, Povlishock JT, Buki A (2005) Spectrin breakdown products in the cerebrospinal fluid in severe head injury—preliminary observations. Acta Neurochir (Wien) 147:855–861

    CAS  Google Scholar 

  49. Fasulo L, Ugolini G, Visintin M, Bradbury A, Brancolini C, Verzillo V, Novak M, Cattaneo A (2000) The neuronal microtubule-associated protein tau is a substrate for caspase-3 and an effector of apoptosis. J Neurochem 75:624–633

    CAS  PubMed  Google Scholar 

  50. Fatouros PP, Marmarou A (1999) Use of magnetic resonance imaging for in vivo measurements of water content in human brain: method and normal values. J Neurosurg 90:109–115

    CAS  PubMed  Google Scholar 

  51. Field AS, Hasan K, Jellison BJ, Arfanakis K, Alexander AL (2003) Diffusion tensor imaging in an infant with traumatic brain swelling. AJNR Am J Neuroradiol 24:1461–1464

    PubMed  Google Scholar 

  52. Finkelstein E, Corso P, Miller T (2006) The incidence and economic burden of injuries in the United States. Oxford University Press, New York

    Google Scholar 

  53. Finsterer J, Exner M, Rumpold H (2004) Cerebrospinal fluid neuron-specific enolase in non-selected patients. Scand J Clin Lab Invest 64:553–558

    CAS  PubMed  Google Scholar 

  54. Fletcher L, Rider CC, Taylor CB (1976) Enolase isoenzymes. III. Chromatographic and immunological characteristics of rat brain enolase. Biochim Biophys Acta 452:245–252

    CAS  PubMed  Google Scholar 

  55. Formisano R, Carlesimo GA, Sabbadini M, Loasses A, Penta F, Vinicola V, Caltagirone C (2004) Clinical predictors and neuropsychological outcome in severe traumatic brain injury patients. Acta Neurochir (Wien) 146:457–462

    CAS  Google Scholar 

  56. Franz G, Beer R, Kampfl A, Engelhardt K, Schmutzhard E, Ulmer H, Deisenhammer F (2003) Amyloid beta 1–42 and tau in cerebrospinal fluid after severe traumatic brain injury. Neurology 60:1457–1461

    CAS  PubMed  Google Scholar 

  57. Gabbita SP, Scheff SW, Menard RM, Roberts K, Fugaccia I, Zemlan FP (2005) Cleaved-tau: a biomarker of neuronal damage after traumatic brain injury. J Neurotrauma 22:83–94

    PubMed  Google Scholar 

  58. Ghajar J (2000) Traumatic brain injury. Lancet 356:923–929

    CAS  PubMed  Google Scholar 

  59. Glenner GG, Wong CW (1984) Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120:885–890

    CAS  PubMed  Google Scholar 

  60. Goedert M, Spillantini MG, Jakes R, Rutherford D, Crowther RA (1989) Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease. Neuron 3:519–526

    CAS  PubMed  Google Scholar 

  61. Goodman SR, Zimmer WE, Clark MB, Zagon IS, Barker JE, Bloom ML (1995) Brain spectrin: of mice and men. Brain Res Bull 36:593–606

    CAS  PubMed  Google Scholar 

  62. Hackbarth RM, Rzeszutko KM, Sturm G, Donders J, Kuldanek AS, Sanfilippo DJ (2002) Survival and functional outcome in pediatric traumatic brain injury: a retrospective review and analysis of predictive factors. Crit Care Med 30:1630–1635

    PubMed  Google Scholar 

  63. Hardemark HG, Ericsson N, Kotwica Z, Rundstrom G, Mendel-Hartvig I, Olsson Y, Pahlman S, Persson L (1989) S-100 protein and neuron-specific enolase in CSF after experimental traumatic or focal ischemic brain damage. J Neurosurg 71:727–731

    CAS  PubMed  Google Scholar 

  64. Harris AS, Croall DE, Morrow JS (1988) The calmodulin-binding site in alpha-fodrin is near the calcium-dependent protease-I cleavage site. J Biol Chem 263:15754–15761

    CAS  PubMed  Google Scholar 

  65. Haviland J, Russell RI (1997) Outcome after severe non-accidental head injury. Arch Dis Child 77:504–507

    CAS  PubMed  Google Scholar 

  66. Hayakata T, Shiozaki T, Tasaki O, Ikegawa H, Inoue Y, Toshiyuki F, Hosotubo H, Kieko F, Yamashita T (2004) Changes in CSF S100B and cytokine concentrations in early-phase severe traumatic brain injury. Shock 22:102–107

    CAS  PubMed  Google Scholar 

  67. Herrmann M, Curio N, Jost S, Wunderlich MT, Synowitz H, Wallesch CW (1999) Protein S-100B and neuron specific enolase as early neurobiochemical markers of the severity of traumatic brain injury. Restor Neurol Neurosci 14:109–114

    CAS  PubMed  Google Scholar 

  68. 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 31:2670–2677

    CAS  PubMed  Google Scholar 

  69. Holmberg B, Johnels B, Blennow K, Rosengren L (2003) Cerebrospinal fluid Abeta42 is reduced in multiple system atrophy but normal in Parkinson's disease and progressive supranuclear palsy. Mov Disord 18:186–190

    PubMed  Google Scholar 

  70. Horsburgh K, Cole GM, Yang F, Savage MJ, Greenberg BD, Gentleman SM, Graham DI, Nicoll JA (2000) beta-amyloid (Abeta)42(43), abeta42, abeta40 and apoE immunostaining of plaques in fatal head injury. Neuropathol Appl Neurobiol 26:124–132

    CAS  PubMed  Google Scholar 

  71. Horsburgh K, Graham DI, Stewart J, Nicoll JA (1999) Influence of apolipoprotein E genotype on neuronal damage and apoE immunoreactivity in human hippocampus following global ischemia. J Neuropathol Exp Neurol 58:227–234

    CAS  PubMed  Google Scholar 

  72. Horsburgh K, McCarron MO, White F, Nicoll JA (2000) The role of apolipoprotein E in Alzheimer's disease, acute brain injury and cerebrovascular disease: evidence of common mechanisms and utility of animal models. Neurobiol Aging 21:245–255

    CAS  PubMed  Google Scholar 

  73. Huisman TA (2003) Diffusion-weighted imaging: basic concepts and application in cerebral stroke and head trauma. Eur Radiol 13:2283–2297

    PubMed  Google Scholar 

  74. Ingebrigtsen T, Romner B (2002) Biochemical serum markers of traumatic brain injury. J Trauma 52:798–808

    CAS  PubMed  Google Scholar 

  75. Ingebrigtsen T, Romner B (2003) Biochemical serum markers for brain damage: a short review with emphasis on clinical utility in mild head injury. Restor Neurol Neurosci 21:171–176

    CAS  PubMed  Google Scholar 

  76. Ingebrigtsen T, Romner B, Kongstad P, Langbakk B (1995) Increased serum concentrations of protein S-100 after minor head injury: a biochemical serum marker with prognostic value? J Neurol Neurosurg Psychiatry 59:103–104

    CAS  PubMed  Google Scholar 

  77. Ingebrigtsen T, Romner B, Marup-Jensen S, Dons M, Lundqvist C, Bellner J, Alling C, Borgesen SE (2000) The clinical value of serum S-100 protein measurements in minor head injury: a Scandinavian multicentre study. Brain Inj 14:1047–1055

    CAS  PubMed  Google Scholar 

  78. Jensen M, Schroder J, Blomberg M, Engvall B, Pantel J, Ida N, Basun H, Wahlund LO, Werle E (1999) Cerebrospinal fluid A beta42 is increased early in sporadic Alzheimer's disease and declines with disease progression. Ann Neurol 45:504–511

    CAS  PubMed  Google Scholar 

  79. Kampfl A, Posmantur R, Nixon R, Grynspan F, Zhao X, Liu SJ, Newcomb JK, Clifton GL, Hayes RL (1996) mu-calpain activation and calpain-mediated cytoskeletal proteolysis following traumatic brain injury. J Neurochem 67:1575–1583

    CAS  PubMed  Google Scholar 

  80. Kanai M, Matsubara E, Isoe K, Urakami K, Nakashima K, Arai H, Sasaki H, Abe K, Iwatsubo T (1998) Longitudinal study of cerebrospinal fluid levels of tau, A beta1–40, and A beta1–42(43) in Alzheimer's disease: a study in Japan. Ann Neurol 44:17–26

    CAS  PubMed  Google Scholar 

  81. Kavalci C, Pekdemir M, Durukan P, Ilhan N, Yildiz M, Serhatlioglu S, Seckin D (2007) The value of serum tau protein for the diagnosis of intracranial injury in minor head trauma. Am J Emerg Med 25:391–395

    PubMed  Google Scholar 

  82. Kay AD, Petzold A, Kerr M, Keir G, Thompson E, Nicoll JA (2003) Alterations in cerebrospinal fluid apolipoprotein E and amyloid beta-protein after traumatic brain injury. J Neurotrauma 20:943–952

    PubMed  Google Scholar 

  83. Kay AD, Petzold A, Kerr M, Keir G, Thompson EJ, Nicoll JA (2003) Cerebrospinal fluid apolipoprotein E concentration decreases after traumatic brain injury. J Neurotrauma 20:243–250

    PubMed  Google Scholar 

  84. King WJ, MacKay M, Sirnick A (2003) Shaken baby syndrome in Canada: clinical characteristics and outcomes of hospital cases. CMAJ 168:155–159

    PubMed  Google Scholar 

  85. Korfias S, Stranjalis G, Boviatsis E, Psachoulia C, Jullien G, Gregson B, Mendelow AD, Sakas DE (2007) Serum S-100B protein monitoring in patients with severe traumatic brain injury. Intensive Care Med 33:255–260

    CAS  PubMed  Google Scholar 

  86. Kosik KS, Finch EA (1987) MAP2 and tau segregate into dendritic and axonal domains after the elaboration of morphologically distinct neurites: an immunocytochemical study of cultured rat cerebrum. J Neurosci 7:3142–3153

    CAS  PubMed  Google Scholar 

  87. Laskowitz DT, Sheng H, Bart RD, Joyner KA, Roses AD, Warner DS (1997) Apolipoprotein E-deficient mice have increased susceptibility to focal cerebral ischemia. J Cereb Blood Flow Metab 17:753–758

    CAS  PubMed  Google Scholar 

  88. Laskowitz DT, Thekdi AD, Thekdi SD, Han SK, Myers JK, Pizzo SV, Bennett ER (2001) Downregulation of microglial activation by apolipoprotein E and apoE-mimetic peptides. Exp Neurol 167:74–85

    CAS  PubMed  Google Scholar 

  89. Leviton A, Dammann O (2002) Brain damage markers in children. Neurobiological and clinical aspects. Acta Paediatr 91:9–13

    CAS  PubMed  Google Scholar 

  90. Li N, Shen JK, Zhao WG, Cai Y, Li YF, Zhan SK (2004) S-100B and neuron specific enolase in outcome prediction of severe head injury. Chin J Traumatol 7:156–158

    PubMed  Google Scholar 

  91. LRJ HPN (1975) The slow component of axonal transport. Identification of major structural polypeptides of the axon and their generality among mammalian neurons. J Cell Biol 66:351–366

    Google Scholar 

  92. Lynch JR, Morgan D, Mance J, Matthew WD, Laskowitz DT (2001) Apolipoprotein E modulates glial activation and the endogenous central nervous system inflammatory response. J Neuroimmunol 114:107–113

    CAS  PubMed  Google Scholar 

  93. Marmarou A, Portella G, Barzo P, Signoretti S, Fatouros P, Beaumont A, Jiang T, Bullock R (2000) Distinguishing between cellular and vasogenic edema in head injured patients with focal lesions using magnetic resonance imaging. Acta Neurochir Suppl 76:349–351

    CAS  PubMed  Google Scholar 

  94. McKeating EG, Andrews PJ, Mascia L (1998) Relationship of neuron specific enolase and protein S-100 concentrations in systemic and jugular venous serum to injury severity and outcome after traumatic brain injury. Acta Neurochir Suppl 71:117–119

    CAS  PubMed  Google Scholar 

  95. mer-Wahlin I, Herbst A, Lindoff C, Thorngren-Jerneck K, Marsal K, Alling C (2001) Brain-specific NSE and S-100 proteins in umbilical blood after normal delivery. Clin Chim Acta 304:57–63

    Google Scholar 

  96. 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 45:138–141

    CAS  PubMed  Google Scholar 

  97. Miyata M, Smith JD (1996) Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides. Nat Genet 14:55–61

    CAS  PubMed  Google Scholar 

  98. Mori T, Morimoto K, Hayakawa T, Ushio Y, Mogami H, Sekiguchi K (1978) Radioimmunoassay of astroprotein (an astrocyte-specific cerebroprotein) in cerebrospinal fluid and its clinical significance. Neurol Med Chir (Tokyo) 18:25–31

    CAS  Google Scholar 

  99. Morris MW, Smith S, Cressman J, Ancheta J (2000) Evaluation of infants with subdural hematoma who lack external evidence of abuse. Pediatrics 105:549–553

    CAS  PubMed  Google Scholar 

  100. Motter R, Vigo-Pelfrey C, Kholodenko D, Barbour R, Johnson-Wood K, Galasko D, Chang L, Miller B, Clark C, Green R (1995) Reduction of beta-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer's disease. Ann Neurol 38:643–648

    CAS  PubMed  Google Scholar 

  101. Muller K, Townend W, Biasca N, Unden J, Waterloo K, Romner B, Ingebrigtsen T (2007) S100B serum level predicts computed tomography findings after minor head injury. J Trauma 62:1452–1456

    Google Scholar 

  102. Murray CJ, Lopez AD (1997) Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet 349:1436–1442

    CAS  PubMed  Google Scholar 

  103. 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 20:463–468

    PubMed  Google Scholar 

  104. Nathan BP, Bellosta S, Sanan DA, Weisgraber KH, Mahley RW, Pitas RE (1994) Differential effects of apolipoproteins E3 and E4 on neuronal growth in vitro. Science 264:850–852

    CAS  PubMed  Google Scholar 

  105. Netto CB, Conte S, Leite MC, Pires C, Martins TL, Vidal P, Benfato MS, Giugliani R, Goncalves CA (2006) Serum S100B protein is increased in fasting rats. Arch Med Res 37:683–686

    CAS  PubMed  Google Scholar 

  106. Newcomb JK, Kampfl A, Posmantur RM, Zhao X, Pike BR, Liu SJ, Clifton GL, Hayes RL (1997) Immunohistochemical study of calpain-mediated breakdown products to alpha-spectrin following controlled cortical impact injury in the rat. J Neurotrauma 14:369–383

    CAS  PubMed  Google Scholar 

  107. Nicoll JA, Martin L, Stewart J, Murray LS, Love S, Kennedy PG (2001) Involvement of apolipoprotein E in herpes simplex encephalitis. Neuroreport 12:695–698

    CAS  PubMed  Google Scholar 

  108. Nygaard O, Langbakk B, Romner B (1998) Neuron-specific enolase concentrations in serum and cerebrospinal fluid in patients with no previous history of neurological disorder. Scand J Clin Lab Invest 58:183–186

    CAS  PubMed  Google Scholar 

  109. 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 240:85–91

    CAS  PubMed  Google Scholar 

  110. Olsson A, Csajbok L, Ost M, Hoglund K, Nylen K, Rosengren L, Nellgard B, Blennow K (2004) Marked increase of beta-amyloid(1–42) and amyloid precursor protein in ventricular cerebrospinal fluid after severe traumatic brain injury. J Neurol 251:870–876

    CAS  PubMed  Google Scholar 

  111. Ost M, Nylen K, Csajbok L, Ohrfelt AO, Tullberg M, Wikkelso C, Nellgard P, Rosengren L, Blennow K (2006) Initial CSF total tau correlates with 1-year outcome in patients with traumatic brain injury. Neurology 67:1600–1604

    CAS  PubMed  Google Scholar 

  112. Otto M, Esselmann H, Schulz-Shaeffer W, Neumann M, Schroter A, Ratzka P, Cepek L, Zerr I, Steinacker P (2000) Decreased beta-amyloid1–42 in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. Neurology 54:1099–1102

    CAS  PubMed  Google Scholar 

  113. Paterakis K, Karantanas AH, Komnos A, Volikas Z (2000) Outcome of patients with diffuse axonal injury: the significance and prognostic value of MRI in the acute phase. J Trauma 49:1071–1075

    CAS  PubMed  Google Scholar 

  114. Pelinka LE, Bahrami S, Szalay L, Umar F, Redl H (2003) Hemorrhagic shock induces an S 100 B increase associated with shock severity. Shock 19:422–426

    CAS  PubMed  Google Scholar 

  115. Pelinka LE, Harada N, Szalay L, Jafarmadar M, Redl H, Bahrami S (2004) Release of S100B differs during ischemia and reperfusion of the liver, the gut, and the kidney in rats. Shock 21:72–76

    CAS  PubMed  Google Scholar 

  116. Pelinka LE, Hertz H, Mauritz W, Harada N, Jafarmadar M, Albrecht M, Redl H, Bahrami S (2005) Nonspecific increase of systemic neuron-specific enolase after trauma: clinical and experimental findings. Shock 24:119–123

    CAS  PubMed  Google Scholar 

  117. Pelinka LE, Jafarmadar M, Redl H, Bahrami S (2004) Neuron-specific-enolase is increased in plasma after hemorrhagic shock and after bilateral femur fracture without traumatic brain injury in the rat. Shock 22:88–91

    CAS  PubMed  Google Scholar 

  118. 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 21:1553–1561

    PubMed  Google Scholar 

  119. Pelinka LE, Kroepfl A, Schmidhammer R, Krenn M, Buchinger W, Redl H, Raabe A (2004) Glial fibrillary acidic protein in serum after traumatic brain injury and multiple trauma. J Trauma 57:1006–1012

    CAS  PubMed  Google Scholar 

  120. Peterfalvi A, Farkas O, Tamas A, Zsombok A, Reglodi D, Buki A, Lengradi I, Doczi T (2003) Effects of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) in a rat model of diffuse axonal injury. Ideggyogy Sz 56:1977

    Google Scholar 

  121. Pike BR, Flint J, Dutta S, Johnson E, Wang KK, Hayes RL (2001) Accumulation of non-erythroid alpha II-spectrin and calpain-cleaved alpha II-spectrin breakdown products in cerebrospinal fluid after traumatic brain injury in rats. J Neurochem 78:1297–1306

    CAS  PubMed  Google Scholar 

  122. Pike BR, Zhao X, Newcomb JK, Glenn CC, Anderson DK, Hayes RL (2000) Stretch injury causes calpain and caspase-3 activation and necrotic and apoptotic cell death in septo-hippocampal cell cultures. J Neurotrauma 17:283–298

    CAS  PubMed  Google Scholar 

  123. Pike BR, Zhao X, Newcomb JK, Posmantur RM, Wang KK, Hayes RL (1998) Regional calpain and caspase-3 proteolysis of alpha-spectrin after traumatic brain injury. Neuroreport 9:2437–2442

    CAS  PubMed  Google Scholar 

  124. Pineda JA, Lewis SB, Valadka AB, Papa L, Hannay HJ, Heaton SC, Demery JA, Liu MC, Aikman JM (2007) Clinical significance of alpha II-spectrin breakdown products in cerebrospinal fluid after severe traumatic brain injury. J Neurotrauma 24:354–366

    PubMed  Google Scholar 

  125. Povlishock JT, Christman CW (1995) The pathobiology of traumatically induced axonal injury in animals and humans: a review of current thoughts. J Neurotrauma 12:555–564

    CAS  PubMed  Google Scholar 

  126. Povlishock JT, Pettus EH (1996) Traumatically induced axonal damage: evidence for enduring changes in axolemmal permeability with associated cytoskeletal change. Acta Neurochir Suppl 66:81–86

    CAS  PubMed  Google Scholar 

  127. Raabe A, Grolms C, Sorge O, Zimmermann M, Seifert V (1999) Serum S-100B protein in severe head injury. Neurosurgery 45:477–483

    CAS  PubMed  Google Scholar 

  128. Raabe A, Menon DK, Gupta S, Czosnyka M, Pickard JD (1998) Jugular venous and arterial concentrations of serum S-100B protein in patients with severe head injury: a pilot study. J Neurol Neurosurg Psychiatry 65:930–932

    CAS  PubMed  Google Scholar 

  129. Raby CA, Morganti-Kossmann MC, Kossmann T, Stahel PF, Watson MD, Evans LM, Mehta PD, Spiegel K, Kuo YM (1998) Traumatic brain injury increases beta-amyloid peptide 1–42 in cerebrospinal fluid. J Neurochem 71:2505–2509

    Article  CAS  PubMed  Google Scholar 

  130. Rifai N, Christenson RH, Gelman BB, Silverman LM (1987) Changes in cerebrospinal fluid IgG and apolipoprotein E indices in patients with multiple sclerosis during demyelination and remyelination. Clin Chem 33:1155–1157

    CAS  PubMed  Google Scholar 

  131. Ringger NC, O'Steen BE, Brabham JG, Silver X, Pineda J, Wang KK, Hayes RL, Papa L (2004) A novel marker for traumatic brain injury: CSF alpha II-spectrin breakdown product levels. J Neurotrauma 21:1443–1456

    CAS  PubMed  Google Scholar 

  132. Roberts GW, Gentleman SM, Lynch A, Graham DI (1991) beta A4 amyloid protein deposition in brain after head trauma. Lancet 338:1422–1423

    CAS  PubMed  Google Scholar 

  133. Romner B, Ingebrigtsen T, Kongstad P, Borgesen SE (2000) Traumatic brain damage: serum S-100 protein measurements related to neuroradiological findings. J Neurotrauma 17:641–647

    CAS  PubMed  Google Scholar 

  134. Ross SA, Cunningham RT, Johnston CF, Rowlands BJ (1996) Neuron-specific enolase as an aid to outcome prediction in head injury. Br J Neurosurg 10:471–476

    CAS  PubMed  Google Scholar 

  135. Rothoerl RD, Brawanski A, Woertgen C (2000) S-100B protein serum levels after controlled cortical impact injury in the rat. Acta Neurochir (Wien) 142:199–203

    CAS  Google Scholar 

  136. Rothoerl RD, Woertgen C, Holzschuh M, Metz C, Brawanski A (1998) S-100 serum levels after minor and major head injury. J Trauma 45:765–767

    CAS  PubMed  Google Scholar 

  137. Saatman KE, Bozyczko-Coyne D, Marcy V, Siman R, McIntosh TK (1996) Prolonged calpain-mediated spectrin breakdown occurs regionally following experimental brain injury in the rat. J Neuropathol Exp Neurol 55:850–860

    CAS  PubMed  Google Scholar 

  138. Sandor J, Szucs M, Kiss I, Ember I, Csepregi G, Futo J, Vimlati L, Pal J, Buki A (2003) Risk factors for fatal outcome in subdural hemorrhage. Ideggyogy Sz 56:386–395

    PubMed  Google Scholar 

  139. Savola O, Hillbom M (2003) Early predictors of post-concussion symptoms in patients with mild head injury. Eur J Neurol 10:175–181

    CAS  PubMed  Google Scholar 

  140. Sawauchi S, Taya K, Murakami S, Ishi T, Ohtsuka T, Kato N, Kaku S, Tanaka T, Morooka S (2005) Serum S-100B protein and neuron-specific enolase after traumatic brain injury. No Shinkei Geka 33:1073–1080

    CAS  PubMed  Google Scholar 

  141. Schaan M, Jaksche H, Boszczyk B (2002) Predictors of outcome in head injury: proposal of a new scaling system. J Trauma 52:667–674

    PubMed  Google Scholar 

  142. Schauwecker PE, Cogen JP, Jiang T, Cheng HW, Collier TJ, McNeill TH (1998) Differential regulation of astrocytic mRNAs in the rat striatum after lesions of the cortex or substantia nigra. Exp Neurol 149:87–96

    CAS  PubMed  Google Scholar 

  143. Schmechel D, Marangos PJ, Brightman M (1978) Neuron-specific enolase is a molecular marker for peripheral and central neuroendocrine cells. Nature 276:834–836

    CAS  PubMed  Google Scholar 

  144. Schofield PW, Tang M, Marder K, Bell K, Dooneief G, Chun M, Sano M, Stern Y, Mayeux R (1997) Alzheimer's disease after remote head injury: an incidence study. J Neurol Neurosurg Psychiatry 62:119–124

    CAS  PubMed  Google Scholar 

  145. Schuhmann MU, Stiller D, Skardelly M, Bernarding J, Klinge PM, Samii A, Samii M, Brinker T (2003) Metabolic changes in the vicinity of brain contusions: a proton magnetic resonance spectroscopy and histology study. J Neurotrauma 20:725–743

    PubMed  Google Scholar 

  146. Sergeant N, Delacourte A, Buee L (2005) Tau protein as a differential biomarker of tauopathies. Biochim Biophys Acta 1739:179–197

    CAS  PubMed  Google Scholar 

  147. Shaw GJ, Jauch EC, Zemlan FP (2002) Serum cleaved tau protein levels and clinical outcome in adult patients with closed head injury. Ann Emerg Med 39:254–257

    PubMed  Google Scholar 

  148. Shore PM, Berger RP, Varma S, Janesko KL, Wisniewski SR, Clark RS, Adelson PD, Thomas NJ, Lai YC (2007) Cerebrospinal fluid biomarkers versus Glasgow coma scale and Glasgow outcome scale in pediatric traumatic brain injury: the role of young age and inflicted injury. J Neurotrauma 24:75–86

    PubMed  Google Scholar 

  149. Sjogren M, Davidsson P, Wallin A, Granerus AK, Grundstrom E, Askmark H, Vanmechelen E, Blennow K (2002) Decreased CSF-beta-amyloid 42 in Alzheimer's disease and amyotrophic lateral sclerosis may reflect mismetabolism of beta-amyloid induced by disparate mechanisms. Dement Geriatr Cogn Disord 13:112–118

    PubMed  Google Scholar 

  150. Skogseid IM, Nordby HK, Urdal P, Paus E, Lilleaas F (1992) Increased serum creatine kinase BB and neuron specific enolase following head injury indicates brain damage. Acta Neurochir (Wien) 115:106–111

    CAS  Google Scholar 

  151. Spinella PC, Dominguez T, Drott HR, Huh J, McCormick L, Rajendra A, Argon J, McIntosh T, Helfaer M (2003) S-100beta protein-serum levels in healthy children and its association with outcome in pediatric traumatic brain injury. Crit Care Med 31:939–945

    CAS  PubMed  Google Scholar 

  152. Stalnacke BM, Elgh E, Sojka P (2005) One-year follow-up of mild traumatic brain injury: cognition, disability and life satisfaction of patients seeking consultation. J Rehabil Med 39:405–411

    Google Scholar 

  153. Stapert S, de KJ, Houx P, Menheere P, Twijnstra A, Jolles J (2005) S-100B concentration is not related to neurocognitive performance in the first month after mild traumatic brain injury. Eur Neurol 53:22–26

    CAS  PubMed  Google Scholar 

  154. Stone JR, Okonkwo DO, Singleton RH, Mutlu LK, Helm GA, Povlishock JT (2002) Caspase-3-mediated cleavage of amyloid precursor protein and formation of amyloid Beta peptide in traumatic axonal injury. J Neurotrauma 19:601–614

    PubMed  Google Scholar 

  155. Stranjalis G, Korfias S, Papapetrou C, Kouyialis A, Boviatsis E, Psachoulia C, Sakas DE (2004) Elevated serum S-100B protein as a predictor of failure to short-term return to work or activities after mild head injury. J Neurotrauma 21:1070–1075

    PubMed  Google Scholar 

  156. Tagliaferri F, Compagnone C, Korsic M, Servadei F, Kraus J (2006) A systematic review of brain injury epidemiology in Europe. Acta Neurochir (Wien) 148:255–268

    CAS  Google Scholar 

  157. Takanashi Y, Shinonaga M (2001) Magnetic resonance imaging for surgical consideration of acute head injury. J Clin Neurosci 8:240–244

    CAS  PubMed  Google Scholar 

  158. Tamaoka A, Kondo T, Odaka A, Sahara N, Sawamura N, Ozawa K, Suzuki N, Shoji S, Mori H (1994) Biochemical evidence for the long-tail form (A beta 1–42/43) of amyloid beta protein as a seed molecule in cerebral deposits of Alzheimer's disease. Biochem Biophys Res Commun 205:834–842

    CAS  PubMed  Google Scholar 

  159. Teasdale GM, Nicoll JA, Murray G, Fiddes M (1997) Association of apolipoprotein E polymorphism with outcome after head injury. Lancet 350:1069–1071

    CAS  PubMed  Google Scholar 

  160. Tolias CM, Bullock MR (2004) Critical appraisal of neuroprotection trials in head injury: what have we learned? NeuroRx 1:71–79

    PubMed  Google Scholar 

  161. Townend W, Ingebrigtsen T (2006) Head injury outcome prediction: a role for protein S-100B? Injury 37:1098–1108

    PubMed  Google Scholar 

  162. Ucar T, Baykal A, Akyuz M, Dosemeci L, Toptas B (2004) Comparison of serum and cerebrospinal fluid protein S-100b levels after severe head injury and their prognostic importance. J Trauma 57:95–98

    CAS  PubMed  Google Scholar 

  163. 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 6:94–99

    Google Scholar 

  164. Vajtr D, Prusa R, Kukacka J, Houst'ava L, Samal F, Pelichovska M, Strejc P, Toupalik P (2007) Evaluation of relevance in concussion and damage of health by monitoring of neuron specific enolase and S-100b protein. Soud Lek 52:43–46

    CAS  PubMed  Google Scholar 

  165. Van Nostrand WE, Wagner SL, Shankle WR, Farrow JS, Dick M, Rozemuller JM, Kuiper MA, Wolters EC, Zimmerman J (1992) Decreased levels of soluble amyloid beta-protein precursor in cerebrospinal fluid of live Alzheimer disease patients. Proc Natl Acad Sci U S A 89:2551–2555

    PubMed  Google Scholar 

  166. Vos PE, Lamers KJ, Hendriks JC, van HM, Beems T, Zimmerman C, van GW, de RH, Biert J, Verbeek MM (2004) Glial and neuronal proteins in serum predict outcome after severe traumatic brain injury. Neurology 62:1303–1310

    CAS  PubMed  Google Scholar 

  167. Wang KK, Posmantur R, Nath R, McGinnis K, Whitton M, Talanian RV, Glantz SB, Morrow JS (1998) Simultaneous degradation of alpha II- and beta II-spectrin by caspase 3 (CPP32) in apoptotic cells. J Biol Chem 273:22490–22497

    CAS  PubMed  Google Scholar 

  168. Whitaker-Azmitia PM, Wingate M, Borella A, Gerlai R, Roder J, Azmitia EC (1997) Transgenic mice overexpressing the neurotrophic factor S-100 beta show neuronal cytoskeletal and behavioral signs of altered aging processes: implications for Alzheimer's disease and Down's syndrome. Brain Res 776:51–60

    CAS  PubMed  Google Scholar 

  169. White F, Nicoll JA, Horsburgh K (2001) Alterations in ApoE and ApoJ in relation to degeneration and regeneration in a mouse model of entorhinal cortex lesion. Exp Neurol 169:307–318

    CAS  PubMed  Google Scholar 

  170. Wiesmann M, Missler U, Gottmann D, Gehring S (1998) Plasma S-100b protein concentration in healthy adults is age- and sex-independent. Clin Chem 44:1056–1058

    CAS  PubMed  Google Scholar 

  171. Woertgen C, Rothoerl RD, Brawanski A (2001) Neuron-specific enolase serum levels after controlled cortical impact injury in the rat. J Neurotrauma 18:569–573

    CAS  PubMed  Google Scholar 

  172. Woertgen C, Rothoerl RD, Holzschuh M, Metz C, Brawanski A (1997) Comparison of serial S-100 and NSE serum measurements after severe head injury. Acta Neurochir (Wien) 139:1161–1164

    CAS  Google Scholar 

  173. 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 47:1126–1130

    CAS  PubMed  Google Scholar 

  174. Woertgen C, Rothoerl RD, Wiesmann M, Missler U, Brawanski A (2002) Glial and neuronal serum markers after controlled cortical impact injury in the rat. Acta Neurochir Suppl 81:205–207

    CAS  PubMed  Google Scholar 

  175. Yakovlev AG, Faden AI (2004) Mechanisms of neural cell death: implications for development of neuroprotective treatment strategies. NeuroRx 1:5–16

    PubMed  Google Scholar 

  176. Yamazaki Y, Yada K, Morii S, Kitahara T, Ohwada T (1995) Diagnostic significance of serum neuron-specific enolase and myelin basic protein assay in patients with acute head injury. Surg Neurol 43:267–270

    CAS  PubMed  Google Scholar 

  177. Zemlan FP, Jauch EC, Mulchahey JJ, Gabbita SP, Rosenberg WS, Speciale SG, Zuccarello M (2002) C-tau biomarker of neuronal damage in severe brain injured patients: association with elevated intracranial pressure and clinical outcome. Brain Res 947:131–139

    CAS  PubMed  Google Scholar 

  178. Zemlan FP, Rosenberg WS, Luebbe PA, Campbell TA, Dean GE, Weiner NE, Cohen JA, Rudick RA, Woo D (1999) Quantification of axonal damage in traumatic brain injury: affinity purification and characterization of cerebrospinal fluid tau proteins. J Neurochem 72:741–750

    CAS  PubMed  Google Scholar 

  179. Zimmer DB, Cornwall EH, Landar A, Song W (1995) The S100 protein family: history, function, and expression. Brain Res Bull 37:417–429

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the Hungarian Science Funds (OTKA T048724/2005 and OTKA 72240). The authors wish to thank to Joel H. Greenberg Ph.D., Katalin Kariko Ph.D., and Brian Edlow M.D. for critical review of this manuscript.

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Kövesdi, E., Lückl, J., Bukovics, P. et al. Update on protein biomarkers in traumatic brain injury with emphasis on clinical use in adults and pediatrics. Acta Neurochir 152, 1–17 (2010). https://doi.org/10.1007/s00701-009-0463-6

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