Biomarkers of mild traumatic brain injury in cerebrospinal fluid and blood (original) (raw)

• Roozenbeek, B., Maas, A. I. & Menon, D. K. Opinion: Changing patterns in the epidemiology of traumatic brain injury. Nat. Rev. Neurol. http://dx.doi/org/nrneurol.2013.22
• American Congress of Rehabilitation Medicine. Definition of mild traumatic brain injury. J. Head Trauma Rehabil. 8, 86–87 (1993).
• Blumbergs, P. C. et al. Staining of amyloid precursor protein to study axonal damage in mild head injury. Lancet 344, 1055–1056 (1994).
  Article CAS PubMed Google Scholar
• Browne, K. D., Chen, X. H., Meaney, D. F. & Smith, D. H. Mild traumatic brain injury and diffuse axonal injury in swine. J. Neurotrauma 28, 1747–1755 (2011).
  Article PubMed PubMed Central Google Scholar
• Baugh, C. M. et al. Chronic traumatic encephalopathy: neurodegeneration following repetitive concussive and subconcussive brain trauma. Brain Imaging Behav. 6, 244–254 (2012).
  Article PubMed Google Scholar
• Gavett, B. E., Stern, R. A. & McKee, A. C. Chronic traumatic encephalopathy: a potential late effect of sport-related concussive and subconcussive head trauma. Clin. Sports Med. 30, 179–188 (2011).
  Article PubMed PubMed Central Google Scholar
• Goldstein, L. E. et al. Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. Sci. Transl. Med. 4, 134ra160 (2012).
  Google Scholar
• McCrory, P. et al. Consensus statement on concussion in sport—the 3rd International Conference on Concussion in Sport held in Zurich, November 2008. Phys. Sportsmed. 37, 141–159 (2009).
  Article PubMed Google Scholar
• Røe, C., Sveen, U., Alvsåker, K. & Bautz-Holter, E. Post-concussion symptoms after mild traumatic brain injury: influence of demographic factors and injury severity in a 1-year cohort study. Disabil. Rehabil. 31, 1235–1243 (2009).
  Article PubMed Google Scholar
• Williams, W. H., Potter, S. & Ryland, H. Mild traumatic brain injury and postconcussion syndrome: a neuropsychological perspective. J. Neurol. Neurosurg. Psychiatry 81, 1116–1122 (2010).
  Article PubMed Google Scholar
• Meaney, D. F. & Smith, D. H. Biomechanics of concussion. Clin. Sports Med. 30, 19–31 (2011).
  Article PubMed PubMed Central Google Scholar
• Smith, D. H. & Meaney, D. F. Axonal damage in traumatic brain injury. The Neuroscientist 6, 483–495 (2000).
  Article Google Scholar
• Johnson, V. E., Stewart, W. & Smith, D. H. Axonal pathology in traumatic brain injury. Exp. Neurol. (2012).
• Wolf, J. A., Stys, P. K., Lusardi, T., Meaney, D. & Smith, D. H. Traumatic axonal injury induces calcium influx modulated by tetrodotoxin-sensitive sodium channels. J. Neurosci. 21, 1923–1930 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Saatman, K. E., Creed, J. & Raghupathi, R. Calpain as a therapeutic target in traumatic brain injury. Neurotherapeutics 7, 31–42 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Giza, C. C. & Hovda, D. A. The neurometabolic cascade of concussion. J. Athl. Train. 36, 228–235 (2001).
  PubMed PubMed Central Google Scholar
• Barkhoudarian, G., Hovda, D. A. & Giza, C. C. The molecular pathophysiology of concussive brain injury. Clin. Sports Med. 30, 33–48 (2011).
  Article PubMed Google Scholar
• Tang-Schomer, M. D., Patel, A. R., Baas, P. W. & Smith, D. H. Mechanical breaking of microtubules in axons during dynamic stretch injury underlies delayed elasticity, microtubule disassembly, and axon degeneration. FASEB J. 24, 1401–1410 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Tang-Schomer, M. D., Johnson, V. E., Baas, P. W., Stewart, W. & Smith, D. H. Partial interruption of axonal transport due to microtubule breakage accounts for the formation of periodic varicosities after traumatic axonal injury. Exp. Neurol. 233, 364–372 (2012).
  Article PubMed Google Scholar
• Povlishock, J. T., Becker, D. P., Cheng, C. L. & Vaughan, G. W. Axonal change in minor head injury. J. Neuropathol. Exp. Neurol. 42, 225–242 (1983).
  Article CAS PubMed Google Scholar
• Povlishock, J. T. & Becker, D. P. Fate of reactive axonal swellings induced by head injury. Lab. Invest. 52, 540–552 (1985).
  CAS PubMed Google Scholar
• Chen, X. H. et al. Long-term accumulation of amyloid-β, β-secretase, presenilin-1, and caspase-3 in damaged axons following brain trauma. Am. J. Pathol. 165, 357–371 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Lipton, M. L. et al. Multifocal white matter ultrastructural abnormalities in mild traumatic brain injury with cognitive disability: a voxel-wise analysis of diffusion tensor imaging. J. Neurotrauma 25, 1335–1342 (2008).
  Article PubMed Google Scholar
• Niogi, S. N. et al. Extent of microstructural white matter injury in postconcussive syndrome correlates with impaired cognitive reaction time: a 3T diffusion tensor imaging study of mild traumatic brain injury. AJNR Am. J. Neuroradiol. 29, 967–973 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Wilde, E. A. et al. Diffusion tensor imaging of acute mild traumatic brain injury in adolescents. Neurology 70, 948–955 (2008).
  Article CAS PubMed Google Scholar
• New Zealand Guidelines Group Staff, Accident Compensation Corporation (N. Z.) Staff. Traumatic Brain Injury: Diagnosis, Acute Management and Rehabilitation (Accident Compensation Corporation, New Zealand, 2006).
• Iverson, G. L., Gaetz, M., Lovell, M. R. & Collins, M. W. Cumulative effects of concussion in amateur athletes. Brain Inj. 18, 433–443 (2004).
  Article PubMed Google Scholar
• Brooks, W. M. et al. Metabolic and cognitive response to human traumatic brain injury: a quantitative proton magnetic resonance study. J. Neurotrauma 17, 629–640 (2000).
  Article CAS PubMed Google Scholar
• Anderson, V., Catroppa, C., Morse, S., Haritou, F. & Rosenfeld, J. Recovery of intellectual ability following traumatic brain injury in childhood: impact of injury severity and age at injury. Pediatr. Neurosurg. 32, 282–290 (2000).
  Article CAS PubMed Google Scholar
• Prins, M. L. & Hovda, D. A. Developing experimental models to address traumatic brain injury in children. J. Neurotrauma 20, 123–137 (2003).
  Article PubMed Google Scholar
• Duhaime, A. C. Large animal models of traumatic injury to the immature brain. Dev. Neurosci. 28, 380–387 (2006).
  Article CAS PubMed Google Scholar
• Pinto, P. S., Meoded, A., Poretti, A., Tekes, A. & Huisman, T. A. The unique features of traumatic brain injury in children. Review of the characteristics of the pediatric skull and brain, mechanisms of trauma, patterns of injury, complications, and their imaging findings—part 2. J. Neuroimaging 22, e18–e41 (2012).
  Article PubMed Google Scholar
• Pinto, P. S., Poretti, A., Meoded, A., Tekes, A. & Huisman, T. A. The unique features of traumatic brain injury in children. Review of the characteristics of the pediatric skull and brain, mechanisms of trauma, patterns of injury, complications and their imaging findings—part 1. J. Neuroimaging 22, e1–e17 (2012).
  Article PubMed Google Scholar
• Martland, H. Punch drunk. JAMA 91, 1103–1107 (1928).
  Article Google Scholar
• Roberts, A. H. Brain Damage in Boxers: a Study of the Prevalence of Traumatic Encephalopathy Among Ex-Professional Boxers (Pitman Medical Scientific Publications, London, 1969).
  Google Scholar
• Jordan, B. D. et al. Apolipoprotein E ε4 associated with chronic traumatic brain injury in boxing. JAMA 278, 136–140 (1997).
  Article CAS PubMed Google Scholar
• Stern, R. A. et al. Long-term consequences of repetitive brain trauma: chronic traumatic encephalopathy. PM R 3, S460–S467 (2011).
  Article PubMed Google Scholar
• Smith, D. H., Johnson, V. E. & Stewart, W. The chronic neuropathologies of single and repetitive traumatic brain injury: potential substrates of dementia? Nat. Rev. Neurol. (in press).
• Gavett, B. E. et al. Clinical appraisal of chronic traumatic encephalopathy: current perspectives and future directions. Curr. Opin. Neurol. 24, 525–531 (2011).
  Article PubMed Google Scholar
• Jordan, B. D. Chronic traumatic brain injury associated with boxing. Semin. Neurol. 20, 179–185 (2000).
  Article CAS PubMed Google Scholar
• Mendez, M. F. The neuropsychiatric aspects of boxing. Int. J. Psychiatry Med. 25, 249–262 (1995).
  Article CAS PubMed Google Scholar
• Roberts, G. W., Allsop, D. & Bruton, C. The occult aftermath of boxing. J. Neurol. Neurosurg. Psychiatry 53, 373–378 (1990).
  Article CAS PubMed PubMed Central Google Scholar
• Tokuda, T., Ikeda, S., Yanagisawa, N., Ihara, Y. & Glenner, G. G. Re-examination of ex-boxers' brains using immunohistochemistry with antibodies to amyloid β-protein and tau protein. Acta Neuropathol. 82, 280–285 (1991).
  Article CAS PubMed Google Scholar
• Johnson, V. E., Stewart, W. & Smith, D. H. Traumatic brain injury and amyloid-β pathology: a link to Alzheimer's disease? Nat. Rev. Neurosci. 11, 361–370 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Johnson, V. E., Stewart, W. & Smith, D. H. Widespread tau and amyloid-β pathology many years after a single traumatic brain injury in humans. Brain Pathol. 22, 142–149 (2012).
  Article CAS PubMed Google Scholar
• Johnson, V. E., Stewart, W., Trojanowski, J. Q. & Smith, D. H. Acute and chronically increased immunoreactivity to phosphorylation-independent but not pathological TDP-43 after a single traumatic brain injury in humans. Acta Neuropathol. 122, 715–726 (2011).
  Article PubMed PubMed Central Google Scholar
• Jordan, B. D. Clinical spectrum of sports-related traumatic brain injury. Nat. Rev. Neurol. (in press).
• Blennow, K., Hampel, H., Weiner, M. & Zetterberg, H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat. Rev. Neurol. 6, 131–144 (2010).
  Article CAS PubMed Google Scholar
• Abbott, N. J., Rönnbäck, L. & Hansson, E. Astrocyte-endothelial interactions at the blood–brain barrier. Nat. Rev. Neurosci. 7, 41–53 (2006).
  Article CAS PubMed Google Scholar
• Tibbling, G., Link, H. & Ohman, S. Principles of albumin and IgG analyses in neurological disorders. I. Establishment of reference values. Scand. J. Clin. Lab. Invest. 37, 385–390 (1977).
  Article CAS PubMed Google Scholar
• Csuka, E. et al. IL-10 levels in cerebrospinal fluid and serum of patients with severe traumatic brain injury: relationship to IL-6, TNF-α, TGF-β1 and blood–brain barrier function. J. Neuroimmunol. 101, 211–221 (1999).
  Article CAS PubMed Google Scholar
• Kossmann, T. et al. Intrathecal and serum interleukin-6 and the acute-phase response in patients with severe traumatic brain injuries. Shock 4, 311–317 (1995).
  Article CAS PubMed Google Scholar
• Blennow, K. et al. No neurochemical evidence of brain injury after blast overpressure by repeated explosions or firing heavy weapons. Acta Neurol. Scand. 123, 245–251 (2011).
  Article CAS PubMed Google Scholar
• Zetterberg, H. et al. Neurochemical aftermath of amateur boxing. Arch. Neurol. 63, 1277–1280 (2006).
  Article PubMed Google Scholar
• Semple, B. D., Bye, N., Rancan, M., Ziebell, J. M. & Morganti-Kossmann, M. C. Role of CCL2 (MCP-1) in traumatic brain injury (TBI): evidence from severe TBI patients and CCL2−/− mice. J. Cereb Blood Flow Metab. 30, 769–782 (2010).
  Article PubMed Google Scholar
• Kirchhoff, C. et al. Cerebrospinal IL-10 concentration is elevated in non-survivors as compared to survivors after severe traumatic brain injury. Eur. J. Med. Res. 13, 464–468 (2008).
  CAS PubMed Google Scholar
• Goodman, J. C., Van, M., Gopinath, S. P. & Robertson, C. S. Pro-inflammatory and pro-apoptotic elements of the neuroinflammatory response are activated in traumatic brain injury. Acta Neurochir. Suppl. 102, 437–439 (2008).
  Article CAS PubMed Google Scholar
• Buttram, S. D. et al. Multiplex assessment of cytokine and chemokine levels in cerebrospinal fluid following severe pediatric traumatic brain injury: effects of moderate hypothermia. J. Neurotrauma 24, 1707–1717 (2007).
  Article PubMed Google Scholar
• Phillips, D. J. et al. Activin A release into cerebrospinal fluid in a subset of patients with severe traumatic brain injury. J. Neurotrauma 23, 1283–1294 (2006).
  Article PubMed Google Scholar
• Maier, B. et al. Delayed elevation of soluble tumor necrosis factor receptors p75 and p55 in cerebrospinal fluid and plasma after traumatic brain injury. Shock 26, 122–127 (2006).
  Article CAS PubMed Google Scholar
• Shiozaki, T. et al. Cerebrospinal fluid concentrations of anti-inflammatory mediators in early-phase severe traumatic brain injury. Shock 23, 406–410 (2005).
  Article CAS PubMed Google Scholar
• Singhal, A. et al. Association between cerebrospinal fluid interleukin-6 concentrations and outcome after severe human traumatic brain injury. J. Neurotrauma 19, 929–937 (2002).
  Article CAS PubMed Google Scholar
• Stahel, P. F. et al. Intrathecal levels of complement-derived soluble membrane attack complex (sC5b-9) correlate with blood–brain barrier dysfunction in patients with traumatic brain injury. J. Neurotrauma 18, 773–781 (2001).
  Article CAS PubMed Google Scholar
• Bell, M. J. et al. Interleukin-6 and interleukin-10 in cerebrospinal fluid after severe traumatic brain injury in children. J. Neurotrauma 14, 451–457 (1997).
  Article CAS PubMed Google Scholar
• Trojanowski, J. Q., Schuck, T., Schmidt, M. L. & Lee, V. M. Distribution of tau proteins in the normal human central and peripheral nervous system. J. Histochem. Cytochem. 37, 209–215 (1989).
  Article CAS PubMed Google Scholar
• Friede, R. L. & Samorajski, T. Axon caliber related to neurofilaments and microtubules in sciatic nerve fibers of rats and mice. Anat. Rec. 167, 379–387 (1970).
  Article CAS PubMed Google Scholar
• Franz, G. et al. Amyloid β1–42 and tau in cerebrospinal fluid after severe traumatic brain injury. Neurology 60, 1457–1461 (2003).
  Article CAS PubMed Google Scholar
• Zemlan, F. P. et al. C-tau biomarker of neuronal damage in severe brain injured patients: association with elevated intracranial pressure and clinical outcome. Brain Res. 947, 131–139 (2002).
  Article CAS PubMed Google Scholar
• Blennow, K. & Nellgård, B. Amyloid β1–42 and tau in cerebrospinal fluid after severe traumatic brain injury. Neurology 62, 159–160 (2004).
  Article PubMed Google Scholar
• Ost, M. et al. Initial CSF total tau correlates with 1-year outcome in patients with traumatic brain injury. Neurology 67, 1600–1604 (2006).
  Article CAS PubMed Google Scholar
• Neselius, S. et al. CSF-biomarkers in Olympic boxing: diagnosis and effects of repetitive head trauma. PLoS ONE 7, e33606 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Liu, Q. et al. Neurofilament proteins in neurodegenerative diseases. Cell. Mol. Life Sci. 61, 3057–3075 (2004).
  Article CAS PubMed Google Scholar
• Siman, R. et al. A panel of neuron-enriched proteins as markers for traumatic brain injury in humans. J. Neurotrauma 26, 1867–1877 (2009).
  Article PubMed PubMed Central Google Scholar
• Olsson, B., Zetterberg, H., Hampel, H. & Blennow, K. Biomarker-based dissection of neurodegenerative diseases. Prog. Neurobiol. 4, 520–534 (2011).
  Article CAS Google Scholar
• Scarna, H. et al. Neuron-specific enolase as a marker of neuronal lesions during various comas in man. Neurochem. Int. 4, 405–411 (1982).
  Article CAS PubMed Google Scholar
• Bohmer, A. E. et al. Neuron-specific enolase, S100B, and glial fibrillary acidic protein levels as outcome predictors in patients with severe traumatic brain injury. Neurosurgery 68, 1624–1631 (2011).
  Article PubMed Google Scholar
• Chiaretti, A. et al. NGF, DCX, and NSE upregulation correlates with severity and outcome of head trauma in children. Neurology 72, 609–616 (2009).
  Article CAS PubMed Google Scholar
• Varma, S. et al. F2-isoprostane and neuron-specific enolase in cerebrospinal fluid after severe traumatic brain injury in infants and children. J. Neurotrauma 20, 781–786 (2003).
  Article PubMed Google Scholar
• Berger, R. P. et al. Neuron-specific enolase and S100B in cerebrospinal fluid after severe traumatic brain injury in infants and children. Pediatrics 109, E31 (2002).
  Article PubMed Google Scholar
• Ross, S. A., Cunningham, R. T., Johnston, C. F. & Rowlands, B. J. Neuron-specific enolase as an aid to outcome prediction in head injury. Br. J. Neurosurg. 10, 471–476 (1996).
  Article CAS PubMed Google Scholar
• Berger, R. P. et al. Identification of inflicted traumatic brain injury in well-appearing infants using serum and cerebrospinal markers: a possible screening tool. Pediatrics 117, 325–332 (2006).
  Article PubMed Google Scholar
• Ramont, L. et al. Effects of hemolysis and storage condition on neuron-specific enolase (NSE) in cerebrospinal fluid and serum: implications in clinical practice. Clin. Chem. Lab. Med. 43, 1215–1217 (2005).
  Article CAS PubMed Google Scholar
• Moore, B. W. & McGregor, D. Chromatographic and electrophoretic fractionation of soluble proteins of brain and liver. J. Biol. Chem. 240, 1647–1653 (1965).
  CAS PubMed Google Scholar
• Isobe, T., Ishioka, N. & Okuyama, T. Structural relation of two S-100 proteins in bovine brain; subunit composition of S.-100A protein. Eur. J. Biochem. 115, 469–474 (1981).
  Article CAS PubMed Google Scholar
• Nylen, K. et al. Serum levels of S100B, S100A1B and S100BB are all related to outcome after severe traumatic brain injury. Acta Neurochir. (Wien) 150, 221–227 (2008).
  Article CAS Google Scholar
• Czeiter, E. et al. Brain injury biomarkers may improve the predictive power of the IMPACT outcome calculator. J. Neurotrauma 29, 1770–1778 (2012).
  Article PubMed PubMed Central Google Scholar
• McKenzie, J. E., Gentleman, S. M., Roberts, G. W., Graham, D. I. & Royston, M. C. Increased numbers of β APP-immunoreactive neurones in the entorhinal cortex after head injury. Neuroreport 6, 161–164 (1994).
  Article CAS PubMed Google Scholar
• Sherriff, F. E., Bridges, L. R. & Sivaloganathan, S. Early detection of axonal injury after human head trauma using immunocytochemistry for β-amyloid precursor protein. Acta Neuropathol. 87, 55–62 (1994).
  Article CAS PubMed Google Scholar
• Gentleman, S. M. et al. Axonal injury: a universal consequence of fatal closed head injury? Acta Neuropathol. 89, 537–543 (1995).
  Article CAS PubMed Google Scholar
• Ahlgren, S., Li, G. L. & Olsson, Y. Accumulation of β-amyloid precursor protein and ubiquitin in axons after spinal cord trauma in humans: immunohistochemical observations on autopsy material. Acta Neuropathol. 92, 49–55 (1996).
  Article CAS PubMed Google Scholar
• Gleckman, A. M., Bell, M. D., Evans, R. J. & Smith, T. W. Diffuse axonal injury in infants with nonaccidental craniocerebral trauma: enhanced detection by β-amyloid precursor protein immunohistochemical staining. Arch. Pathol. Lab. Med. 123, 146–151 (1999).
  CAS PubMed Google Scholar
• McKenzie, K. J. et al. Is β-APP a marker of axonal damage in short-surviving head injury? Acta Neuropathol. 92, 608–613 (1996).
  Article CAS PubMed Google Scholar
• Smith, D. H., Chen, X. H., Iwata, A. & Graham, D. I. Amyloid β accumulation in axons after traumatic brain injury in humans. J. Neurosurg. 98, 1072–1077 (2003).
  Article CAS PubMed Google Scholar
• Uryu, K. et al. Multiple proteins implicated in neurodegenerative diseases accumulate in axons after brain trauma in humans. Exp. Neurol. 208, 185–192 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Chen, X. H., Johnson, V. E., Uryu, K., Trojanowski, J. Q. & Smith, D. H. A lack of amyloid β plaques despite persistent accumulation of amyloid β in axons of long-term survivors of traumatic brain injury. Brain Pathol. 19, 214–223 (2009).
  Article PubMed Google Scholar
• Roberts, G. W., Gentleman, S. M., Lynch, A. & Graham, D. I. β A4 amyloid protein deposition in brain after head trauma. Lancet 338, 1422–1423 (1991).
  Article CAS PubMed Google Scholar
• Graham, D. I., Gentleman, S. M., Lynch, A. & Roberts, G. W. Distribution of β-amyloid protein in the brain following severe head injury. Neuropathol. Appl. Neurobiol. 21, 27–34 (1995).
  Article CAS PubMed Google Scholar
• Horsburgh, K. et al. β-amyloid (Aβ)42(43), Aβ42, Aβ40 and apoE immunostaining of plaques in fatal head injury. Neuropathol. Appl. Neurobiol. 26, 124–132 (2000).
  Article CAS PubMed Google Scholar
• Raby, C. A. et al. Traumatic brain injury increases β-amyloid peptide1–42 in cerebrospinal fluid. J. Neurochem. 71, 2505–2509 (1998).
  Article CAS PubMed Google Scholar
• Olsson, A. et al. Marked increase of β-amyloid1–42 and amyloid precursor protein in ventricular cerebrospinal fluid after severe traumatic brain injury. J. Neurol. 251, 870–876 (2004).
  Article CAS PubMed Google Scholar
• Mortberg, E. et al. Plasma tau protein in comatose patients after cardiac arrest treated with therapeutic hypothermia. Acta Anaesthesiol. Scand. 55, 1132–1138 (2011).
  Article CAS PubMed Google Scholar
• Randall, J. et al. Tau proteins in serum predict neurological outcome after hypoxic brain injury from cardiac arrest: results of a pilot study. Resuscitation http://dx.doi.org/10.1016/j.resuscitation.2012.07.027.
• Rissin, D. M. et al. Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations. Nat. Biotechnol. 28, 595–599 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Mondello, S. et al. Blood-based diagnostics of traumatic brain injuries. Expert Rev. Mol. Diagn. 11, 65–78 (2011).
  Article PubMed PubMed Central Google Scholar
• Kovesdi, E. et al. Update on protein biomarkers in traumatic brain injury with emphasis on clinical use in adults and pediatrics. Acta Neurochir. (Wien) 152, 1–17 (2010).
  Article Google Scholar
• Mussack, T. et al. Significance of Elecsys S100 immunoassay for real-time assessment of traumatic brain damage in multiple trauma patients. Clin. Chem. Lab. Med. 44, 1140–1145 (2006).
  Article CAS PubMed Google Scholar
• Rothoerl, R. D. & Woertgen, C. High serum S100B levels for trauma patients without head injuries. Neurosurgery 49, 1490–1493 (2001).
  Article CAS PubMed Google Scholar
• Anderson, R. E., Hansson, L. O., Nilsson, O., Dijlai-Merzoug, R. & Settergren, G. High serum S100B levels for trauma patients without head injuries. Neurosurgery 48, 1255–1260 (2001).
  CAS PubMed Google Scholar
• Romner, B. & Ingebrigtsen, T. High serum S100B levels for trauma patients without head injuries. Neurosurgery 49, 1490–1493 (2001).
  Article CAS PubMed Google Scholar
• Stalnacke, B. M., Ohlsson, A., Tegner, Y. & Sojka, P. Serum concentrations of two biochemical markers of brain tissue damage S-100B and neurone specific enolase are increased in elite female soccer players after a competitive game. Br. J. Sports Med. 40, 313–316 (2006).
  Article PubMed PubMed Central Google Scholar
• Blyth, B. J. et al. Elevated serum ubiquitin carboxy-terminal hydrolase L1 is associated with abnormal blood–brain barrier function after traumatic brain injury. J. Neurotrauma 28, 2453–2462 (2011).
  Article PubMed Google Scholar
• Metting, Z., Wilczak, N., Rodiger, L. A., Schaaf, J. M. & van der Naalt, J. GFAP and S100B in the acute phase of mild traumatic brain injury. Neurology 78, 1428–1433 (2012).
  Article CAS PubMed Google Scholar
• Berger, R. P. et al. Serum neuron-specific enolase, S100B, and myelin basic protein concentrations after inflicted and noninflicted traumatic brain injury in children. J. Neurosurg. 103, 161–68 (2005).
  Google Scholar
• Zurek, J. & Fedora, M. The usefulness of S100B, NSE, GFAP, NF-H, secretagogin and Hsp70 as a predictive biomarker of outcome in children with traumatic brain injury. Acta Neurochir. (Wien) 154, 193–103 (2012).
  Article Google Scholar
• Zurek, J., Bartlova, L. & Fedora, M. Hyperphosphorylated neurofilament NF-H as a predictor of mortality after brain injury in children. Brain Inj. 25, 221–226 (2011).
  Article PubMed Google Scholar
• Tisdall, M. & Petzold, A. Comment on “chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model”. Sci. Transl. Med. 4, 157le158 (2012).
  Article Google Scholar
• Riederer, B. M., Zagon, I. S. & Goodman, S. R. Brain spectrin(240/235) and brain spectrin(240/235E): two distinct spectrin subtypes with different locations within mammalian neural cells. J. Cell Biol. 102, 2088–2097 (1986).
  Article CAS PubMed Google Scholar
• Pike, B. R. et al. Accumulation of non-erythroid α II-spectrin and calpain-cleaved α II-spectrin breakdown products in cerebrospinal fluid after traumatic brain injury in rats. J. Neurochem. 78, 1297–1306 (2001).
  Article CAS PubMed Google Scholar
• Pineda, J. A. et al. Clinical significance of αII-spectrin breakdown products in cerebrospinal fluid after severe traumatic brain injury. J. Neurotrauma 24, 354–366 (2007).
  Article PubMed Google Scholar
• Farkas, O. et al. Spectrin breakdown products in the cerebrospinal fluid in severe head injury—preliminary observations. Acta Neurochir. (Wien) 147, 855–861 (2005).
  Article CAS Google Scholar
• Mondello, S. et al. αII-spectrin breakdown products (SBDPs): diagnosis and outcome in severe traumatic brain injury patients. J. Neurotrauma 27, 1203–1213 (2010).
  Article PubMed PubMed Central Google Scholar
• Wilkinson, K. D. et al. The neuron-specific protein PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase. Science 246, 670–673 (1989).
  Article CAS PubMed Google Scholar
• Papa, L. et al. Serum levels of ubiquitin C-terminal hydrolase distinguish mild traumatic brain injury from trauma controls and are elevated in mild and moderate traumatic brain injury patients with intracranial lesions and neurosurgical intervention. J. Trauma Acute Care Surg. 72, 1335–1344 (2012).
  Article PubMed PubMed Central Google Scholar
• Ottens, A. K. et al. Neuroproteomics in neurotrauma. Mass Spectrom. Rev. 25, 380–408 (2006).
  Article CAS PubMed Google Scholar
• Pasinetti, G. M., Ho, L., Dooley, C., Abbi, B. & Lange, G. Select non-coding RNA in blood components provide novel clinically accessible biological surrogates for improved identification of traumatic brain injury in OEF/OIF veterans. Am. J. Neurodegener. Dis. 1, 88–98 (2012).
  PubMed PubMed Central Google Scholar
• Corsellis, J. A., Bruton, C. J. & Freeman-Browne, D. The aftermath of boxing. Psychol. Med. 3, 270–303 (1973).
  Article CAS PubMed Google Scholar
• Pollock, N. J., Mirra, S. S., Binder, L. I., Hansen, L. A. & Wood, J. G. Filamentous aggregates in Pick's disease, progressive supranuclear palsy, and Alzheimer's disease share antigenic determinants with microtubule-associated protein, tau. Lancet 2, 1211 (1986).
  Article CAS PubMed Google Scholar
• Hampel, H. et al. Measurement of phosphorylated tau epitopes in the differential diagnosis of Alzheimer disease: a comparative cerebrospinal fluid study. Arch. Gen. Psychiatry 61, 95–102 (2004).
  Article CAS PubMed Google Scholar
• Hall, S. et al. Accuracy of a panel of 5 cerebrospinal fluid biomarkers in the differential diagnosis of patients with dementia and/or parkinsonian disorders. Arch. Neurol., 27, 1–8 (2012).
  Google Scholar
• Dickson, D. W., Kouri, N., Murray, M. E. & Josephs, K. A. Neuropathology of frontotemporal lobar degeneration-tau (FTLD-tau). J. Mol. Neurosci. 45, 384–389 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• King, A. et al. Abnormal TDP-43 expression is identified in the neocortex in cases of dementia pugilistica, but is mainly confined to the limbic system when identified in high and moderate stages of Alzheimer's disease. Neuropathology 30, 408–419 (2010).
  Article PubMed Google Scholar
• McKee, A. C. et al. TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy. J. Neuropathol. Exp. Neurol. 69, 918–929 (2010).
  Article CAS PubMed Google Scholar
• Neumann, M. et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314, 130–133 (2006).
  Article CAS PubMed Google Scholar
• Geser, F. et al. On the development of markers for pathological TDP-43 in amyotrophic lateral sclerosis with and without dementia. Prog. Neurobiol. 95, 649–662 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Guerrero, A. F. & Alfonso, A. Traumatic brain injury-related hypopituitarism: a review and recommendations for screening combat veterans. Mil. Med. 175, 574–580 (2010).
  Article PubMed Google Scholar
• Kelestimur, F. et al. Boxing as a sport activity associated with isolated GH deficiency. J. Endocrinol. Invest. 27, RC28–RC32 (2004).
  Article CAS PubMed Google Scholar
• Tanriverdi, F. et al. Brief communication: pituitary volume and function in competing and retired male boxers. Ann. Intern. Med. 148, 827–831 (2008).
  Article PubMed Google Scholar
• Tanriverdi, F. et al. Kickboxing sport as a new cause of traumatic brain injury-mediated hypopituitarism. Clin. Endocrinol. (Oxf.) 66, 360–366 (2007).
  Article Google Scholar
• Wilkinson, C. W. et al. High prevalence of chronic pituitary and target-organ hormone abnormalities after blast-related mild traumatic brain injury. Front. Neurol. 3, 11 (2012).
  Article PubMed PubMed Central Google Scholar