Skip to main content

Biochemical Markers of Brain Injury

  • Chapter
  • First Online:
Brain Protection in Cardiac Surgery
  • 1109 Accesses

Abstract

Detection of brain injury perioperatively can be a difficult task as it ranges from the very subtle to grossly apparent. Brain injury following cardiopulmonary bypass (CBP) remains a common and serious complication that is often misdiagnosed.1,2 The American College of Cardiology/American Heart Association guidelines for coronary artery bypass graft (CABG) surgery divide postoperative neurologic deficits into two categories.3 Type 1 deficits include major focal neurologic events, stupor and coma. Type 2 deficits describe more global cognitive deficits such as deterioration in intellectual function, memory, and confusion without evidence of focal injury. Type 1 deficits are usually caused by identifiable sources of cerebral hypoxia due to intraoperative hypoperfusion or embolic phenomena. In contrast, the etiology of type 2 deficits is unclear and likely multifactorial; where factors such as hypoxia, time on CPB, age, type of procedure, preoperative creatinine levels, and perioperative inflam­matory response have been implicated in its pathophysiology.4 While physical examination and neuroimaging modalities have proven valuable for the detection and treatment of acute focal brain damage postoperatively, mild and diffuse injuries such as ­neurocognitive decline (NCD) seen in type 2 deficits would benefit from improvements in the early diagnosis and identification of these patients. Neuropsycho­logical tests, the current gold standard for detecting NCD, are complex and difficult to use routinely in the postoperative ­setting. Identifying biochemical surrogate markers for brain dysfunction would greatly assist in the diag­-nosis and timely treatments of patients with this complication.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Ahonen J, Salmenpera M. Brain injury after adult cardiac surgery. Acta Anaesthesiol Scand. Jan 2004;48(1):4-19.

    Article  CAS  PubMed  Google Scholar 

  2. Arrowsmith JE, Grocott HP, Reves JG, Newman MF. Central nervous system complications of cardiac surgery. Br J Anaesth. Mar 2000;84(3):378-393.

    CAS  PubMed  Google Scholar 

  3. Eagle KA, Guyton RA, Davidoff R, et al. ACC/AHA guidelines for coronary artery bypass graft surgery: executive summary and recommendations: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to revise the 1991 guidelines for coronary artery bypass graft surgery). Circulation. Sept 28 1999;100(13):1464-1480.

    CAS  PubMed  Google Scholar 

  4. Murkin JM. Etiology and incidence of brain dysfunction after cardiac surgery. J Cardiothorac Vasc Anesth. Aug 1999;13(4 Suppl 1):12-17. discussion 36-17.

    CAS  PubMed  Google Scholar 

  5. Jonsson H, Johnsson P, Backstrom M, Alling C, Dautovic-Bergh C, Blomquist S. Controversial significance of early S100B levels after cardiac surgery. BMC Neurol. Dec 16 2004;4(1):24.

    Article  PubMed  Google Scholar 

  6. Kalman J, Juhasz A, Bogats G, et al. Elevated levels of inflammatory biomarkers in the cerebrospinal fluid after coronary artery bypass surgery are predictors of cognitive decline. Neurochem Int. Feb 2006;48(3):177-180.

    Article  CAS  PubMed  Google Scholar 

  7. Lloyd CT, Ascione R, Underwood MJ, Gardner F, Black A, Angelini GD. Serum S-100 protein release and neuropsychologic outcome during coronary revascularization on the beating heart: a prospective randomized study. J Thorac Cardiovasc Surg. Jan 2000;119(1):148-154.

    Article  CAS  PubMed  Google Scholar 

  8. Rasmussen LS, Christiansen M, Hansen PB, Moller JT. Do blood levels of neuron-specific enolase and S-100 protein reflect cognitive dysfunction after coronary artery bypass? Acta Anaesthesiol Scand. May 1999;43(5):495-500.

    Article  CAS  PubMed  Google Scholar 

  9. Reiber H. Dynamics of brain-derived proteins in cerebrospinal fluid. Clin Chim Acta. Aug 20 2001;310(2):173-186.

    Article  CAS  PubMed  Google Scholar 

  10. Shaw GJ, Jauch EC, Zemlan FP. Serum cleaved tau protein levels and clinical outcome in adult patients with closed head injury. Ann Emerg Med. Mar 2002;39(3):254-257.

    Article  PubMed  Google Scholar 

  11. Vaage J, Anderson R. Biochemical markers of neurologic injury in cardiac surgery: the rise and fall of S100beta. J Thorac Cardiovasc Surg. Nov 2001;122(5):853-855.

    Article  CAS  PubMed  Google Scholar 

  12. Westaby S, Saatvedt K, White S, et al. Is there a relationship between serum S-100beta protein and neuropsychologic dysfunction after cardiopulmonary bypass? J Thorac Cardiovasc Surg. Jan 2000;119(1):132-137.

    Article  CAS  PubMed  Google Scholar 

  13. Marcantonio ER, Rudolph JL, Culley D, Crosby G, Alsop D, Inouye SK. Serum biomarkers for delirium. J Gerontol A Biol Sci Med Sci. Dec 2006;61(12):1281-1286.

    PubMed  Google Scholar 

  14. Ali MS, Harmer M, Vaughan R. Serum S100 protein as a marker of cerebral damage during cardiac surgery. Br J Anaesth. Aug 2000;85(2):287-298.

    Article  CAS  PubMed  Google Scholar 

  15. Aurell A, Rosengren LE, Karlsson B, Olsson JE, Zbornikova V, Haglid KG. Determination of S-100 and glial fibrillary acidic protein concentrations in cerebrospinal fluid after brain infarction. Stroke. Oct 1991;22(10):1254-1258.

    CAS  PubMed  Google Scholar 

  16. Isobe T, Takahashi K, Okuyama T. S100a0 (alpha alpha) protein is present in neurons of the central and peripheral nervous system. J Neurochem. Nov 1984;43(5):1494-1496.

    Article  CAS  PubMed  Google Scholar 

  17. Usui A, Kato K, Abe T, Murase M, Tanaka M, Takeuchi E. S-100ao protein in blood and urine during open-heart surgery. Clin Chem. Sept 1989;35(9):1942-1944.

    CAS  PubMed  Google Scholar 

  18. Zimmer DB, Cornwall EH, Landar A, Song W. The S100 protein family: history, function, and expression. Brain Res Bull. 1995;37(4):417-429.

    Article  CAS  PubMed  Google Scholar 

  19. Fano G, Mariggio MA, Angelella P, et al. The S-100 protein causes an increase of intracellular calcium and death of PC12 cells. Neuroscience. Apr 1993;53(4):919-925.

    Article  CAS  PubMed  Google Scholar 

  20. Haglid KG, Yang Q, Hamberger A, Bergman S, Widerberg A, Danielsen N. S-100beta stimulates neurite outgrowth in the rat sciatic nerve grafted with acellular muscle transplants. Brain Res. Apr 11 1997;753(2):196-201.

    Article  CAS  PubMed  Google Scholar 

  21. Selinfreund RH, Barger SW, Pledger WJ, Van Eldik LJ. Neurotrophic protein S100 beta stimulates glial cell proliferation. Proc Natl Acad Sci USA. May 1 1991;88(9):3554-3558.

    Article  CAS  PubMed  Google Scholar 

  22. Begaz T, Kyriacou DN, Segal J, Bazarian JJ. Serum biochemical markers for post-concussion syndrome in patients with mild traumatic brain injury. J Neurotrauma. Aug 2006;23(8):1201-1210.

    Article  PubMed  Google Scholar 

  23. Herrmann M, Ebert AD, Galazky I, Wunderlich MT, Kunz WS, Huth C. Neurobehavioral outcome prediction after cardiac surgery: role of neurobiochemical markers of damage to neuronal and glial brain tissue. Stroke. Mar 2000;31(3):645-650.

    CAS  PubMed  Google Scholar 

  24. Gao L, Taha R, Gauvin D, Othmen LB, Wang Y, Blaise G. Postoperative cognitive dysfunction after cardiac surgery. Chest. Nov 2005;128(5):3664-3670.

    Article  PubMed  Google Scholar 

  25. van Engelen BG, Lamers KJ, Gabreels FJ, Wevers RA, van Geel WJ, Borm GF. Age-related changes of neuron-specific enolase, S-100 protein, and myelin basic protein concentrations in cerebrospinal fluid. Clin Chem. June 1992;38(6):813-816.

    PubMed  Google Scholar 

  26. Nygaard O, Langbakk B, Romner B. Neuron-specific enolase concentrations in serum and cerebrospinal fluid in patients with no previous history of neurological disorder. Scand J Clin Lab Invest. May 1998;58(3):183-186.

    Article  CAS  PubMed  Google Scholar 

  27. Jonsson H, Johnsson P, Alling C, Backstrom M, Bergh C, Blomquist S. S100beta after coronary artery surgery: release pattern, source of contamination, and relation to neuropsychological outcome. Ann Thorac Surg. Dec 1999;68(6):2202-2208.

    Article  CAS  PubMed  Google Scholar 

  28. Ingebrigtsen T, Romner B. Serial S-100 protein serum measurements related to early magnetic resonance imaging after minor head injury. Case report. J Neurosurg. Nov 1996;85(5):945-948.

    Article  CAS  PubMed  Google Scholar 

  29. Ueno T, Iguro Y, Yamamoto H, Sakata R, Kakihana Y, Nakamura K. Serial measurement of serum S-100B protein as a marker of cerebral damage after cardiac surgery. Ann Thorac Surg. June 2003;75(6):1892-1897. discussion 1897-1898.

    Article  PubMed  Google Scholar 

  30. Wang KJ, Wu HH, Fang SY, Yang YR, Tseng AC. Serum S-100 beta protein during coronary artery bypass graft surgery with or without cardiopulmonary bypass. Ann Thorac Surg. Oct 2005;80(4):1371-1374.

    Article  PubMed  Google Scholar 

  31. Ramlawi B, Rudolph JL, Mieno S, et al. Serologic markers of brain injury and cognitive function after cardiopulmonary bypass. Ann Surg. Oct 2006;244(4):593-601.

    PubMed  Google Scholar 

  32. Rasmussen LS, Christiansen M, Eliasen K, Sander-Jensen K, Moller JT. Biochemical markers for brain damage after cardiac surgery - time profile and correlation with cognitive dysfunction. Acta Anaesthesiol Scand. May 2002;46(5):547-551.

    Article  CAS  PubMed  Google Scholar 

  33. Whitaker DC, Green AJ, Stygall J, Harrison MJ, Newman SP. Evaluation of an alternative S100b assay for use in cardiac surgery: relationship with microemboli and neuropsychological outcome. Perfusion. July 2007;22(4):267-272.

    Article  CAS  PubMed  Google Scholar 

  34. Muller K, Elverland A, Romner B, et al. Analysis of protein S-100B in serum: a methodological study. Clin Chem Lab Med. 2006;44(9):1111-1114.

    Article  CAS  PubMed  Google Scholar 

  35. Johnsson P, Blomquist S, Luhrs C, et al. Neuron-specific enolase increases in plasma during and immediately after extracorporeal circulation. Ann Thorac Surg. Mar 2000;69(3):750-754.

    Article  CAS  PubMed  Google Scholar 

  36. Herrmann M, Ebert AD, Tober D, Hann J, Huth C. A contrastive analysis of release patterns of biochemical markers of brain damage after coronary artery bypass grafting and valve replacement and their association with the neurobehavioral outcome after cardiac surgery. Eur J Cardiothorac Surg. Nov 1999;16(5):513-518.

    Article  CAS  PubMed  Google Scholar 

  37. Gao F, Harris DN, Sapsed-Byrne S, Sharp S. Neurone-specific enolase and Sangtec 100 assays during cardiac surgery: Part III – dose haemolysis affect their accuracy? Perfusion. May 1997;12(3):171-177.

    CAS  PubMed  Google Scholar 

  38. Sapsed-Byrne S, Gao F, Harris DN. Neurone-specific enolase and Sangtec 100 assays during cardiac surgery: Part II – must samples be spun within 30 min? Perfusion. May 1997;12(3):167-169.

    CAS  PubMed  Google Scholar 

  39. Gao F, Harris DN, Sapsed-Byrne S, Sharp S. Neurone-specific enolase and Sangtec 100 assays during cardiac surgery: Part I—The effects of heparin, protamine and propofol. Perfusion. May 1997;12(3):163-165.

    CAS  PubMed  Google Scholar 

  40. Zeiner A, Holzer M, Sterz F, et al. Mild resuscitative hypothermia to improve neurological outcome after cardiac arrest. A clinical feasibility trial. Hypothermia After Cardiac Arrest (HACA) Study Group. Stroke. Jan 2000;31(1):86-94.

    CAS  PubMed  Google Scholar 

  41. Shaaban-Ali M, Harmer M, Vaughan RS, et al. Changes in serum S100beta protein and Mini-Mental State Examination after cold (28 degrees C) and warm (34 degrees C) cardiopulmonary bypass using different blood gas strategies (alpha-stat and pH-stat). Acta Anaesthesiol Scand. Jan 2002;46(1):10-16.

    CAS  PubMed  Google Scholar 

  42. Grocott HP, Croughwell ND, Amory DW, White WD, Kirchner JL, Newman MF. Cerebral emboli and serum S100beta during cardiac operations. Ann Thorac Surg. June 1998;65(6):1645-1649. discussion 1649-1650.

    Article  CAS  PubMed  Google Scholar 

  43. Jeppsson B, Freund HR, Gimmon Z, James JH, von Meyenfeldt MF, Fischer JE. Blood-brain barrier derangement in sepsis: cause of septic encephalopathy? Am J Surg. Jan 1981;141(1):136-142.

    Article  CAS  PubMed  Google Scholar 

  44. Gillinov AM, Davis EA, Curtis WE, et al. Cardiopulmonary bypass and the blood-brain barrier. An experimental study. J Thorac Cardiovasc Surg. Oct 1992;104(4):1110-1115.

    CAS  PubMed  Google Scholar 

  45. Cremer J, Martin M, Redl H, et al. Systemic inflammatory response syndrome after cardiac operations. Ann Thorac Surg. June 1996;61(6):1714-1720.

    Article  CAS  PubMed  Google Scholar 

  46. Boyle EM Jr, Pohlman TH, Johnson MC, Verrier ED. Endothelial cell injury in cardiovascular surgery: the systemic inflammatory response. Ann Thorac Surg. Jan 1997;63(1):277-284.

    Article  PubMed  Google Scholar 

  47. Lindberg L, Olsson AK, Anderson K, Jogi P. Serum S-100 protein levels after pediatric cardiac operations: a possible new marker for postperfusion cerebral injury. J Thorac Cardiovasc Surg. Aug 1998;116(2):281-285.

    Article  CAS  PubMed  Google Scholar 

  48. Harris DN, Oatridge A, Dob D, Smith PL, Taylor KM, Bydder GM. Cerebral swelling after normothermic cardiopulmonary bypass. Anesthesiology. Feb 1998;88(2):340-345.

    Article  CAS  PubMed  Google Scholar 

  49. Harris DN, Bailey SM, Smith PL, Taylor KM, Oatridge A, Bydder GM. Brain swelling in first hour after coronary artery bypass surgery. Lancet. Sept 4 1993;342(8871):586-587.

    Article  CAS  PubMed  Google Scholar 

  50. Ashraf S, Bhattacharya K, Tian Y, Watterson K. Cytokine and S100B levels in paediatric patients undergoing corrective cardiac surgery with or without total circulatory arrest. Eur J Cardiothorac Surg. July 1999;16(1):32-37.

    Article  CAS  PubMed  Google Scholar 

  51. Ramlawi B, Rudolph JL, Mieno S, et al. C-Reactive protein and inflammatory response associated to neurocognitive decline following cardiac surgery. Surgery. Aug 2006;140(2):221-226.

    Article  PubMed  Google Scholar 

  52. Baufreton C, Allain P, Chevailler A, et al. Brain injury and neuropsychological outcome after coronary artery surgery are affected by complement activation. Ann Thorac Surg. May 2005;79(5):1597-1605.

    Article  PubMed  Google Scholar 

  53. Ben-Abraham R, Weinbroum AA, Dekel B, Paret G. Chemokines and the inflammatory response following ­cardiopulmonary bypass – a new target for therapeutic intervention? – A review. Paediatr Anaesth. Oct 2003;13(8):655-661.

    Article  PubMed  Google Scholar 

  54. Bar-Yosef S, Anders M, Mackensen GB, et al. Aortic atheroma burden and cognitive dysfunction after coronary artery bypass graft surgery. Ann Thorac Surg. Nov 2004;78(5):1556-1562.

    Article  PubMed  Google Scholar 

  55. Ohata T, Sawa Y, Kadoba K, et al. Normothermia has ­beneficial effects in cardiopulmonary bypass attenuating inflammatory reactions. Asaio J. July–Sept 1995;41(3):M288-291.

    Article  CAS  PubMed  Google Scholar 

  56. Aldea GS, Soltow LO, Chandler WL, et al. Limitation of thrombin generation, platelet activation, and inflammation by elimination of cardiotomy suction in patients undergoing coronary artery bypass grafting treated with heparin-bonded circuits. J Thorac Cardiovasc Surg. Apr 2002;123(4):742-755.

    Article  PubMed  Google Scholar 

  57. Rudolph JL, Ramlawi B, Kuchel GA, et al. Chemokines are associated with delirium after cardiac surgery. J Gerontol A Biol Sci Med Sci. Feb 2008;63(2):184-189.

    PubMed  Google Scholar 

  58. Mielck F, Ziarkowski A, Hanekop G, et al. Cerebral inflammatory response during and after cardiac surgery. Eur J Anaesthesiol. May 2005;22(5):347-352.

    Article  CAS  PubMed  Google Scholar 

  59. Berger RP. The use of serum biomarkers to predict outcome after traumatic brain injury in adults and children. J Head Trauma Rehabil. July-Aug 2006;21(4):315-333.

    Article  PubMed  Google Scholar 

  60. Jauch EC, Lindsell C, Broderick J, Fagan SC, Tilley BC, Levine SR. Association of serial biochemical markers with acute ischemic stroke: the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator Stroke Study. Stroke. Oct 2006;37(10):2508-2513.

    Article  CAS  PubMed  Google Scholar 

  61. Bokesch PM, Izykenova GA, Justice JB, Easley KA, Dambinova SA. NMDA receptor antibodies predict adverse neurological outcome after cardiac surgery in high-risk patients. Stroke. June 2006;37(6):1432-1436.

    Article  CAS  PubMed  Google Scholar 

  62. Pelsers MM, Glatz JF. Detection of brain injury by fatty acid-binding proteins. Clin Chem Lab Med. 2005;43(8):802-809.

    Article  CAS  PubMed  Google Scholar 

  63. Pelsers MM, Hanhoff T, Van der Voort D, et al. Brain- and heart-type fatty acid-binding proteins in the brain: tissue distribution and clinical utility. Clin Chem. Sept 2004;50(9):1568-1575.

    Article  CAS  PubMed  Google Scholar 

  64. Zimmermann-Ivol CG, Burkhard PR, Le Floch-Rohr J, Allard L, Hochstrasser DF, Sanchez JC. Fatty acid binding protein as a serum marker for the early diagnosis of stroke: a pilot study. Mol Cell Proteomics. Jan 2004;3(1):66-72.

    CAS  PubMed  Google Scholar 

  65. Wunderlich MT, Hanhoff T, Goertler M, et al. Release of brain-type and heart-type fatty acid-binding proteins in serum after acute ischaemic stroke. J Neurol. June 2005;252(6):718-724.

    Article  CAS  PubMed  Google Scholar 

  66. Florio P, Abella RF, de la Torre T, et al. Perioperative activin A concentrations as a predictive marker of neurologic abnormalities in children after open heart surgery. Clin Chem. May 2007;53(5):982-985.

    Article  CAS  PubMed  Google Scholar 

  67. Abdul-Khaliq H, Schubert S, Stoltenburg-Didinger G, et al. Release patterns of astrocytic and neuronal biochemical markers in serum during and after experimental settings of cardiac surgery. Restor Neurol Neurosci. 2003;21(3-4):141-150.

    CAS  PubMed  Google Scholar 

  68. Harmon D, Eustace N, Ghori K, et al. Plasma concentrations of nitric oxide products and cognitive dysfunction following coronary artery bypass surgery. Eur J Anaesthesiol. Apr 2005;22(4):269-276.

    Article  CAS  PubMed  Google Scholar 

  69. Strittmatter WJ, Bova Hill C. Molecular biology of apolipoprotein E. Curr Opin Lipidol. Apr 2002;13(2):119-123.

    Article  CAS  PubMed  Google Scholar 

  70. O’Donnell HC, Rosand J, Knudsen KA, et al. Apolipoprotein E genotype and the risk of recurrent lobar intracerebral hemorrhage. N Engl J Med. Jan 27 2000;342(4):240-245.

    Article  PubMed  Google Scholar 

  71. Tardiff BE, Newman MF, Saunders AM, et al. Preliminary report of a genetic basis for cognitive decline after cardiac operations. The Neurologic Outcome Research Group of the Duke Heart Center. Ann Thorac Surg. Sept 1997;64(3):715-720.

    Article  CAS  PubMed  Google Scholar 

  72. Hsiung GY, Sadovnick AD, Feldman H. Apolipoprotein E epsilon4 genotype as a risk factor for cognitive decline and dementia: data from the Canadian Study of Health and Aging. Cmaj. Oct 12 2004;171(8):863-867.

    PubMed  Google Scholar 

  73. Kofke WA, Konitzer P, Meng QC, Guo J, Cheung A. The effect of apolipoprotein E genotype on neuron specific enolase and S-100beta levels after cardiac surgery. Anesth Analg. Nov 2004;99(5):1323-1325. table of contents.

    Article  CAS  PubMed  Google Scholar 

  74. Ramlawi B, Otu H, Rudolph JL, et al. Genomic expression pathways associated with brain injury after cardiopulmonary bypass. J Thorac Cardiovasc Surg. Oct 2007;134(4):996-1005.

    Article  CAS  PubMed  Google Scholar 

  75. Bakay RA, Ward AA Jr. Enzymatic changes in serum and cerebrospinal fluid in neurological injury. J Neurosurg. Jan 1983;58(1):27-37.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer London

About this chapter

Cite this chapter

Ramlawi, B., Sellke, F.W. (2011). Biochemical Markers of Brain Injury. In: Bonser, R., Pagano, D., Haverich, A. (eds) Brain Protection in Cardiac Surgery. Springer, London. https://doi.org/10.1007/978-1-84996-293-3_6

Download citation

  • DOI: https://doi.org/10.1007/978-1-84996-293-3_6

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-84996-292-6

  • Online ISBN: 978-1-84996-293-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics