Skip to main content

Molecular and Biochemical Basis of Brain Injury Following Heart Surgery – Interventions for the Future

  • Chapter
  • First Online:
Brain Protection in Cardiac Surgery

Abstract

Cardiac surgical procedures such as coronary artery bypass grafting (CABG), valvular replacement and heart transplantation, as well as many others are life-saving procedures for hundreds of thousands of US patients each year. However, despite this clinical utility, many patients who undergo cardiac surgery suffer neurological injury as a result. In addition to the morbidity and mortality caused by neurological injury, these complications are associated with increases in hospital length of stays, costs, and admissions to rehabilitation facilities.

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. Roach GW, Kanchuger M, Mangano CM, et al. Adverse cerebral outcomes after coronary bypass surgery. Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators. N Engl J Med. 1996;335:1857-1863.

    Article  CAS  PubMed  Google Scholar 

  2. Redmond JM, Greene PS, Goldsborough MA, et al. Neurologic injury in cardiac surgical patients with a history of stroke. Ann Thorac Surg. 1996;61:42-47.

    Article  CAS  PubMed  Google Scholar 

  3. Baumgartner WA. Neuroprotection in cardiac surgery. Ann Thorac Surg. 2005;79:S2254-S2256.

    Article  PubMed  Google Scholar 

  4. Baumgartner WA. Neurocognitive changes after coronary bypass surgery. Circulation. 2007;116:1879-1881.

    Article  PubMed  Google Scholar 

  5. McKhann GM, Grega MA, Borowicz LM Jr, et al. Encephalopathy and stroke after coronary artery bypass grafting: incidence, consequences, and prediction. Arch Neurol. 2002;59:1422-1428.

    Article  PubMed  Google Scholar 

  6. Bigelow WG, Lindsay WK, Greenwood WF. Hypothermia; its possible role in cardiac surgery: an investigation of factors governing survival in dogs at low body temperatures. Ann Surg. 1950;132:849-866.

    Article  CAS  PubMed  Google Scholar 

  7. Bellinger DC, Jonas RA, Rappaport LA, et al. Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. N Engl J Med. 1995;332:549-555.

    Article  CAS  PubMed  Google Scholar 

  8. Drew CE, Anderson IM. Profound hypothermia in cardiac surgery: report of three cases. Lancet. 1959;1:748-750.

    Article  CAS  PubMed  Google Scholar 

  9. Hickey PR. Neurologic sequelae associated with deep hypothermic circulatory arrest. Ann Thorac Surg. 1998;65:S65-S69. discussion S9–70, S4–6.

    Article  CAS  PubMed  Google Scholar 

  10. Redmond JM, Gillinov AM, Zehr KJ, et al. Glutamate excitotoxicity: a mechanism of neurologic injury associated with hypothermic circulatory arrest. J Thorac Cardiovasc Surg. 1994;107:776-786. discussion 86–87.

    CAS  PubMed  Google Scholar 

  11. Olney J. Neurotoxicity of excitatory amino acids. In: McGeer EGOJ, McGeer PL, eds. Kainic Acid as a Tool in Neurobiology. New York: Raven; 1978:95.

    Google Scholar 

  12. Rothman SM, Olney JW. Glutamate and the pathophysiology of hypoxic–ischemic brain damage. Ann Neurol. 1986;19:105-111.

    Article  CAS  PubMed  Google Scholar 

  13. Won SJ, Kim DY, Gwag BJ. Cellular and molecular pathways of ischemic neuronal death. J Biochem Mol Biol. 2002;35:67-86.

    CAS  PubMed  Google Scholar 

  14. Brock MV, Blue ME, Lowenstein CJ, et al. Induction of neuronal nitric oxide after hypothermic circulatory arrest. Ann Thorac Surg. 1996;62:1313-1320.

    Article  CAS  PubMed  Google Scholar 

  15. Montoliu C, Llansola M, Monfort P, et al. Role of nitric oxide and cyclic GMP in glutamate-induced neuronal death. Neurotox Res. 2001;3:179-188.

    Article  CAS  PubMed  Google Scholar 

  16. Tseng EE, Brock MV, Kwon CC, et al. Increased intracerebral excitatory amino acids and nitric oxide after hypothermic circulatory arrest. Ann Thorac Surg. 1999;67:371-376.

    Article  CAS  PubMed  Google Scholar 

  17. Tseng EE, Brock MV, Lange MS, et al. Nitric oxide mediates neurologic injury after hypothermic circulatory arrest. Ann Thorac Surg. 1999;67:65-71.

    Article  CAS  PubMed  Google Scholar 

  18. Endres M, Wang ZQ, Namura S, Waeber C, Moskowitz MA. Ischemic brain injury is mediated by the activation of poly(ADP-ribose)polymerase. J Cereb Blood Flow Metab. 1997;17:1143-1151.

    Article  CAS  PubMed  Google Scholar 

  19. Mandir AS, Poitras MF, Berliner AR, et al. NMDA but not non-NMDA excitotoxicity is mediated by Poly(ADP-ribose) polymerase. J Neurosci. 2000;20:8005-8011.

    CAS  PubMed  Google Scholar 

  20. Pieper AA, Blackshaw S, Clements EE, et al. Poly(ADP-ribosyl)ation basally activated by DNA strand breaks reflects glutamate-nitric oxide neurotransmission. Proc Natl Acad Sci USA. 2000;97:1845-1850.

    Article  CAS  PubMed  Google Scholar 

  21. Zhang Y, Bhavnani BR. Glutamate-induced apoptosis in neuronal cells is mediated via caspase-dependent and independent mechanisms involving calpain and caspase-3 proteases as well as apoptosis inducing factor (AIF) and this process is inhibited by equine estrogens. BMC Neurosci. 2006;7:49.

    Article  PubMed  Google Scholar 

  22. Kroemer G, Galluzzi L, Brenner C. Mitochondrial membrane permeabilization in cell death. Physiol Rev. 2007;87:99-163.

    Article  CAS  PubMed  Google Scholar 

  23. Teshima Y, Akao M, Li RA, et al. Mitochondrial ATP-sensitive potassium channel activation protects cerebellar granule neurons from apoptosis induced by oxidative stress. Stroke. 2003;34:1796-1802.

    Article  CAS  PubMed  Google Scholar 

  24. Christensen T, Diemer NH. Reduction of mitochondrial electron transport complex activity is restricted to the ischemic focus after transient focal cerebral ischemia in rats: a histochemical volumetric analysis. Neurochem Res. 2003; 28:1805-1812.

    Article  CAS  PubMed  Google Scholar 

  25. Penrice J, Lorek A, Cady EB, et al. Proton magnetic resonance spectroscopy of the brain during acute hypoxia-ischemia and delayed cerebral energy failure in the newborn piglet. Pediatr Res. 1997;41:795-802.

    Article  CAS  PubMed  Google Scholar 

  26. Tseng EE, Brock MV, Lange MS, et al. Neuronal nitric oxide synthase inhibition reduces neuronal apoptosis after hypothermic circulatory arrest. Ann Thorac Surg. 1997;64:1639-1647.

    Article  CAS  PubMed  Google Scholar 

  27. Brown PO, Botstein D. Exploring the new world of the genome with DNA microarrays. Nat Genet. 1999;21:33-37.

    Article  CAS  PubMed  Google Scholar 

  28. Stanton LW, Garrard LJ, Damm D, et al. Altered patterns of gene expression in response to myocardial infarction. Circ Res. 2000;86:939-945.

    CAS  PubMed  Google Scholar 

  29. Lee CK, Allison DB, Brand J, Weindruch R, Prolla TA. Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts. Proc Natl Acad Sci USA. 2002;99:14988-14993.

    Article  CAS  PubMed  Google Scholar 

  30. Matzilevich DA, Rall JM, Moore AN, Grill RJ, Dash PK. High-density microarray analysis of hippocampal gene expression following experimental brain injury. J Neurosci Res. 2002;67:646-663.

    Article  CAS  PubMed  Google Scholar 

  31. Soriano MA, Tessier M, Certa U, Gill R. Parallel gene expression monitoring using oligonucleotide probe arrays of multiple transcripts with an animal model of focal ischemia. J Cereb Blood Flow Metab. 2000;20:1045-1055.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  33. Lindblad-Toh K, Wade CM, Mikkelsen TS, et al. Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature. 2005;438:803-819.

    Article  CAS  PubMed  Google Scholar 

  34. McNamara J. Drugs effective in the therapy of the epilepsies. In: Hardman JGLL, ed. The Pharmacological Basis of Therapeutics. New York: McGraw-Hill; 1996:461-486.

    Google Scholar 

  35. Jeong MR, Hashimoto R, Senatorov VV, et al. Valproic acid, a mood stabilizer and anticonvulsant, protects rat cerebral cortical neurons from spontaneous cell death: a role of histone deacetylase inhibition. FEBS Lett. 2003;542:74-78.

    Article  CAS  PubMed  Google Scholar 

  36. Ren M, Leng Y, Jeong M, Leeds PR, Chuang DM. Valproic acid reduces brain damage induced by transient focal cerebral ischemia in rats: potential roles of histone deacetylase inhibition and heat shock protein induction. J Neurochem. 2004;89:1358-1367.

    Article  CAS  PubMed  Google Scholar 

  37. Ryu H, Lee J, Olofsson BA, et al. Histone deacetylase inhibitors prevent oxidative neuronal death independent of expanded polyglutamine repeats via an Sp1-dependent pathway. Proc Natl Acad Sci USA. 2003;100:4281-4286.

    Article  CAS  PubMed  Google Scholar 

  38. Williams JA, Barreiro CJ, Nwakanma LU, et al. Valproic acid prevents brain injury in a canine model of hypothermic circulatory arrest: a promising new approach to neuroprotection during cardiac surgery. Ann Thorac Surg. 2006;81:2235-2241. discussion 41–42.

    Article  PubMed  Google Scholar 

  39. Sheikh AM, Barrett C, Villamizar N, et al. Proteomics of cerebral injury in a neonatal model of cardiopulmonary bypass with deep hypothermic circulatory arrest. J Thorac Cardiovasc Surg. 2006;132:820-828.

    Article  CAS  PubMed  Google Scholar 

  40. Wang KK, Ottens AK, Liu MC, et al. Proteomic identification of biomarkers of traumatic brain injury. Expert Rev Proteomics. 2005;2:603-614.

    Article  CAS  PubMed  Google Scholar 

  41. Liu MC, Akle V, Zheng W, et al. Comparing calpain- and caspase-3-mediated degradation patterns in traumatic brain injury by differential proteome analysis. Biochem J. 2006;394:715-725.

    Article  CAS  PubMed  Google Scholar 

  42. Goodman SR, Zimmer WE, Clark MB, Zagon IS, Barker JE, Bloom ML. Brain spectrin: of mice and men. Brain Res Bull. 1995;36:593-606.

    Article  CAS  PubMed  Google Scholar 

  43. Riederer BM, Zagon IS, Goodman SR. Brain spectrin(240/235) and brain spectrin(240/235E): two distinct spectrin subtypes with different locations within mammalian neural cells. J Cell Biol. 1986;102:2088-2097.

    Article  CAS  PubMed  Google Scholar 

  44. Wang KK, Posmantur R, Nath R, et al. Simultaneous degradation of alphaII- and betaII-spectrin by caspase 3 (CPP32) in apoptotic cells. J Biol Chem. 1998;273:22490-22497.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  46. Nath R, Probert A Jr, McGinnis KM, Wang KK. Evidence for activation of caspase-3-like protease in excitotoxin- and hypoxia/hypoglycemia-injured neurons. J Neurochem. 1998;71:186-195.

    Article  CAS  PubMed  Google Scholar 

  47. Hall ED, Sullivan PG, Gibson TR, Pavel KM, Thompson BM, Scheff SW. Spatial and temporal characteristics of neurodegeneration after controlled cortical impact in mice: more than a focal brain injury. J Neurotrauma. 2005;22:252-265.

    Article  PubMed  Google Scholar 

  48. Pike BR, Flint J, Dutta S, Johnson E, Wang KK, Hayes RL. 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. 2001;78:1297-1306.

    Article  CAS  PubMed  Google Scholar 

  49. Selnes OA, Grega MA, Borowicz LM Jr, et al. Cognitive outcomes three years after coronary artery bypass surgery: a comparison of on-pump coronary artery bypass graft surgery and nonsurgical controls. Ann Thorac Surg. 2005;79:1201-1209.

    Article  PubMed  Google Scholar 

  50. Selnes OA, Grega MA, Bailey MM, et al. Cognition 6 years after surgical or medical therapy for coronary artery disease. Ann Neurol. 2008;63:581-590.

    Article  PubMed  Google Scholar 

  51. Mullges W, Babin-Ebell J, Reents W, Toyka KV. Cognitive performance after coronary artery bypass grafting: a follow-up study. Neurology. 2002;59:741-743.

    PubMed  Google Scholar 

  52. Wahrborg P, Booth JE, Clayton T, et al. Neuropsychological outcome after percutaneous coronary intervention or coronary artery bypass grafting: results from the Stent or Surgery (SoS) Trial. Circulation. 2004;110:3411-3417.

    Article  PubMed  Google Scholar 

  53. Weiss ES, Wang KKW, Allen JG, et al. Alpha II-spectrin breakdown products serve as novel markers of brain injury severity in a canine model of hypothermic circulatory arrest. Ann Thorac Surg. 2009;88(2):543-550.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Eric S. Weiss .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer London

About this chapter

Cite this chapter

Weiss, E.S., Baumgartner, W.A. (2011). Molecular and Biochemical Basis of Brain Injury Following Heart Surgery – Interventions for the Future. 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_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-84996-293-3_1

  • 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