Skip to main content

The clinical significance of acute brain injury in subarachnoid hemorrhage and opportunity for intervention

  • Conference paper
Cerebral Hemorrhage

Part of the book series: Acta Neurochirurgica Supplementum ((NEUROCHIRURGICA,volume 105))

Abstract

Aneurysmal subarachnoid hemorrhage (SAH) is a devastating neurological event that accounts for 3-7% of all strokes and carries a mortality rate as high as 40%. Delayed cerebral vasospasm has traditionally been recognized as the most treatable cause of morbidity and mortality from SAH. However, evidence is mounting that the physiological and cellular events of acute brain injury, which occur during the 24-72 h following aneurysm rupture, make significant contributions to patient outcomes, and may even be a more significant factor than delayed cerebral vasospasm. Acute brain injury in aneurysmal SAH is the result of physiological derangements such as increased intracranial pressure and decreased cerebral blood flow that result in global cerebral ischemia, and lead to the acute development of edema, oxidative stress, inflammation, apopto-sis, and infarction. The consequence of these events is often death or significant neurological disability. In this study of acute brain injury, we elucidate some of the complex molecular signaling pathways responsible for these poor outcomes. Continued research in this area and the development of therapies to interrupt these cascades should be a major focus in the future as we continue to seek effective therapies for aneurysmal SAH.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Arora M, Chen L, Paglia M, Gallagher I, Allen JE, Vyas YM, Ray A, Ray P (2006) Simvastatin promotes Th2-type responses through the induction of the chitinase family member Ym1 in dendritic cells. Proc Natl Acad Sci USA 103: 7777–7782

    Article  PubMed  CAS  Google Scholar 

  2. Becker KJ, Kindrick DL, Lester MP, Shea C, Ye ZC (2005) Sensitization to brain antigens after stroke is augmented by lipo-polysaccharide. J Cereb Blood Flow Metab 25: 1634–1644

    Article  PubMed  CAS  Google Scholar 

  3. Becker KJ, McCarron RM, Ruetzler C, Laban O, Sternberg E, Flanders KC, Hallenbeck JM (1997) Immunologic tolerance to myelin basic protein decreases stroke size after transient focal cerebral ischemia. Proc Natl Acad Sci USA 94: 10873–10878

    Article  PubMed  CAS  Google Scholar 

  4. Broderick JP, Brott TG, Duldner JE, Tomsick T, Leach A (1994) Initial and recurrent bleeding are the major causes of death following subarachnoid hemorrhage. Stroke 25: 1342–1347

    PubMed  CAS  Google Scholar 

  5. Busch E, Beaulieu C, de Crespigny A, Moseley ME (1998) Diffusion MR imaging during acute subarachnoid hemorrhage in rats. Stroke 29: 2155–2161

    PubMed  CAS  Google Scholar 

  6. Cahill J, Calvert JW, Zhang JH (2006) Mechanisms of early brain injury after subarachnoid hemorrhage. J Cereb Blood Flow Metab 26: 1341–1353

    Article  PubMed  CAS  Google Scholar 

  7. Claassen J, Carhuapoma JR, Kreiter KT, Du EY, Connolly ES, Mayer SA (2002) Global cerebral edema after subarachnoid hemorrhage: frequency, predictors, and impact on outcome. Stroke 33: 1225–1232

    Article  PubMed  Google Scholar 

  8. Claassen J, Vu A, Kreiter KT, Kowalski RG, Du EY, Ostapkovich N, Fitzsimmons BF, Connolly ES, Mayer SA (2004) Effect of acute physiologic derangements on outcome after subarachnoid hemorrhage. Crit Care Med 32: 832–838

    Article  PubMed  Google Scholar 

  9. Endo H, Nito C, Kamada H, Yu F, Chan PH (2007) Reduction in oxi dative stress by superoxide dismutase overexpression attenuates acute brain injury after subarachnoid hemorrhage via activation of Akt/glycogen synthase kinase-3beta survival signaling. J Cereb Blood Flow Metab 27: 975–982

    PubMed  CAS  Google Scholar 

  10. Feigin VL, Anderson N, Rinkel GJ, Algra A, van Gijn J, Bennett DA (2005) Corticosteroids for aneurysmal subarachnoid haemorrhage and primary intracerebral haemorrhage. Cochrane Database Syst Rev (3): CD004583

    Google Scholar 

  11. Feigin VL, Lawes CM, Bennett DA, Anderson CS (2003) Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century. Lancet Neurol 2: 43–53

    Article  PubMed  Google Scholar 

  12. Figueroa S, Oset-Gasque MJ, Arce C, Martinez-Honduvilla CJ, González MP (2006) Mitochondrial involvement in nitric oxide-induced cellular death in cortical neurons in culture. J Neurosci Res 83: 441–449

    Article  PubMed  CAS  Google Scholar 

  13. Gee JM, Kalil A, Shea C, Becker KJ (2007) Lymphocytes: potential mediators of postischemic injury and neuroprotection. Stroke 38: 783–788

    Article  PubMed  Google Scholar 

  14. Germanò A, Imperatore C, d’Avella D, Costa G, Tomasello F (1998) Antivasospastic and brain-protective effects of a hydroxyl radical scavenger (AVS) after experimental subarachnoid hemorrhage. J Neurosurg 88: 1075–1081

    PubMed  Google Scholar 

  15. Hakamada-Taguchi R, Uehara Y, Kuribayashi K, Numabe A, Saito K, Negoro H, Fujita T, Toyo-oka T, Kato T (2003) Inhibition of hydroxymethylglutaryl-coenzyme a reductase reduces Th1 development and promotes Th2 development. Circ Res 93: 948–956

    Article  PubMed  CAS  Google Scholar 

  16. Haley EC Jr, Kassell NF, Apperson-Hansen C, Maile MH, Alves WM (1997) A randomized double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in North America. J Neurosurg 86: 467–474

    PubMed  CAS  Google Scholar 

  17. Hendrix S, Nitsch R (2007) The role of T helper cells in neuroprotection and regeneration. J Neuroimmunol 184: 100–112

    Article  PubMed  CAS  Google Scholar 

  18. Heuer GG, Smith MJ, Elliott JP, Winn HR, LeRoux PD (2004) Relationship between intracranial pressure and other clinical variablesin patients with aneurysmal subarachnoid hemorrhage. J Neurosurg 101: 408–416

    PubMed  Google Scholar 

  19. Hop JW, Rinkel GJ, Algra A, van Gijn J (1997) Case-fatality rates and functional outcome after subarachnoid hemorrhage: a systematic review. Stroke 28: 660–664

    PubMed  CAS  Google Scholar 

  20. Horstmann S, Su Y, Koziol J, Meyding-Lamadé U, Nagel S, Wagner S (2006) MMP-2 and MMP-9 levels in peripheral blood after subarachnoid hemorrhage. J Neurol Sci 251: 82–86

    Article  PubMed  CAS  Google Scholar 

  21. Hütter BO, Kreitschmann-Andermahr I, Mayfrank L, Rohde V, Spetzger U, Gilsbach JM (1999) Functional outcome after aneurysmal subarachnoid hemorrhage. Acta Neurochir Suppl 72: 157–174

    PubMed  Google Scholar 

  22. Imperatore C, Germanò A, d’ Avella D, Tomasello F, Costa G (2000) Effects of the radical scavenger AVS on behavioral and BBB changes after experimental subarachnoid hemorrhage. Life Sci 66: 779–790

    Article  PubMed  CAS  Google Scholar 

  23. Kamiya K, Kuyama H, Symon L (1983) An experimental study of the acute stage of subarachnoid hemorrhage. J Neurosurg 59: 917–924

    PubMed  CAS  Google Scholar 

  24. Kassell NF, Haley EC Jr, Apperson-Hansen C, Alves WM (1996) Randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in Europe, Australia, and New Zealand. J Neurosurg 84: 221–228

    PubMed  CAS  Google Scholar 

  25. Kassell NF, Torner JC, Haley EC Jr, Jane JA, Adams HP, Kongable GL (1990) The international cooperative study on the timing of aneurysm surgery. Part 1: Overall management results. J Neurosurg 73: 18–36

    PubMed  CAS  Google Scholar 

  26. Kreiter KT, Copeland D, Bernardini GL, Bates JE, Peery S, Claassen J, Du YE, Stern Y, Connolly ES, Mayer SA (2002) Predictors of cognitive dysfunction after subarachnoid hemorrhage. Stroke 33: 200–208

    Article  PubMed  Google Scholar 

  27. Kubota T, Handa Y, Tsuchida A, Kaneko M, Kobayashi H, Kubota T (1993) The kinetics of lymphocyte subsets and macrophages in subarachnoid space after subarachnoid hemorrhage in rats. Stroke 24: 1993–2001

    PubMed  CAS  Google Scholar 

  28. Kusaka G, Ishikawa M, Nanda A, Granger DN, Zhang JH (2004) Signaling pathways for early brain injury after subarachnoid hemorrhage. J Cereb Blood Flow Metab 24: 916–925

    Article  PubMed  CAS  Google Scholar 

  29. Lagares A, Gómez PA, Lobato RD, Alén JF, Alday R, Campollo J (2001) Prognostic factors on hospital admission after spontaneous subarachnoid haemorrhage. Acta Neurochir (Wien) 143: 665–672

    Article  CAS  Google Scholar 

  30. Lanzino G, Kassell NF (1999) Double-blind, randomized, vehicle-controlled study of high-dose tirilazad mesylate in women with aneurysmal subarachnoid hemorrhage. Part II: A cooperative study in North America. J Neurosurg 90: 1018–1024

    PubMed  CAS  Google Scholar 

  31. Lanzino G, Kassell NF, Dorsch NW, Pasqualin A, Brandt L, Schmiedek P, Truskowski LL, Alves WM (1999) Double-blind, randomized, vehicle-controlled study of high-dose tirilazad mesylate in women with aneurysmal subarachnoid hemorrhage. Part I: A cooperative study in Europe, Australia, New Zealand, and South Africa. J Neurosurg 90: 1011–1017

    PubMed  CAS  Google Scholar 

  32. Macdonald RL (2007) Prevention of cerebral vasospasm after aneurysmal subarachnoid hemorrhage with clazosentan, and ednothelin receptor antagonist (abstract #800). Neurosurgery 59: a453

    Article  Google Scholar 

  33. Macdonald RL (2007) Randomized trial of clazosentan for prevention vasospasm after aneurysmal subarachnoid hemorrhage (abstract #462). Stroke 38: a453–a607

    Article  CAS  Google Scholar 

  34. Mandal M, Mandal A, Das S, Chakraborti T, Sajal C (2003) Clinical implications of matrix metalloproteinases. Mol Cell Biochem 252: 305–329

    Article  PubMed  CAS  Google Scholar 

  35. Mathiesen T, Lefvert AK (1996) Cerebrospinal fluid and blood lymphocyte subpopulations following subarachnoid haemorrhage. Br J Neurosurg 10: 89–92

    Article  PubMed  CAS  Google Scholar 

  36. Mayhan WG (1999) VEGF increases permeability of the blood-brain barrier via a nitric oxide synthase/cGMP-dependent pathway. Am J Physiol 276: C1148–C1153

    PubMed  CAS  Google Scholar 

  37. McGirt MJ, Lynch JR, Blessing R, Warner DS, Friedman AH, Laskowitz DT (2002) Serum von Willebrand factor, matrix metal-loproteinase-9, and vascular endothelial growth factor levels predict the onset of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Neurosurgery 51: 1128–1135

    Article  PubMed  Google Scholar 

  38. Mocco J, Prickett CS, Komotar RJ, Connolly ES, Mayer SA (2007) Potential mechanisms and clinical significance of global cerebral edema following aneurysmal subarachnoid hemorrhage. Neurosurg Focus 22: E7

    Article  PubMed  CAS  Google Scholar 

  39. Nakayama T, Illoh K, Ruetzler C, Auh S, Sokoloff L, Hallenbeck J (2007) Intranasal administration of E-selectin to induce immuno-logical tolerization can suppress subarachnoid hemorrhage-induced vasospasm implicating immune and inflammatory mechanisms in its genesis. Brain Res 1132: 177–184

    Article  PubMed  CAS  Google Scholar 

  40. Oruckaptan HH, Caner HH, Kilinc K, Ozgen T (2000) No apparent role for neutrophils and neutrophil-derived myeloperoxidase in experimental subarachnoid haemorrhage and vasospasm: a preliminary study. Acta Neurochir (Wien) 142: 83–90

    Article  CAS  Google Scholar 

  41. Ostrowski RP, Colohan AR, Zhang JH (2006) Molecular mechanisms of early brain injury after subarachnoid hemorrhage. Neurol Res 28: 399–414

    Article  PubMed  CAS  Google Scholar 

  42. Park S, Yamaguchi M, Zhou C, Calvert JW, Tang J, Zhang JH (2004) Neurovascular protection reduces early brain injury after subarachnoid hemorrhage. Stroke 35: 2412–2417

    Article  PubMed  CAS  Google Scholar 

  43. Pickard JD, Murray GD, Illingworth R, Shaw MD, Teasdale GM, Foy PM, Humphrey PR, Lang DA, Nelson R, Richards P (1989) Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial. BMJ 298: 636–642

    PubMed  CAS  Google Scholar 

  44. Prunell GF, Svendgaard NA, Alkass K, Mathiesen T (2005) Delayed cell death related to acute cerebral blood flow changes following subarachnoid hemorrhage in the rat brain. J Neurosurg 102: 1046–1054

    PubMed  Google Scholar 

  45. Rabinstein AA, Weigand S, Atkinson JL, Wijdicks EF (2005) Patterns of cerebral infarction in aneurysmal subarachnoid hemorrhage. Stroke 36: 992–997

    Article  PubMed  Google Scholar 

  46. Rosenberg GA (1995) Matrix metalloproteinases in brain injury. J Neurotrauma 12: 833–842

    Article  PubMed  CAS  Google Scholar 

  47. Rosenberg GA, Yang Y (2007) Vasogenic edema due to tight junction disruption by matrix metalloproteinases in cerebral ischemia.Neurosurg Focus 22: E4

    Article  PubMed  Google Scholar 

  48. Satoh M, Date I, Ohmoto T, Perkins E, Parent AD (2005) The expression and activation of matrix metalloproteinase-1 after subarachnoid haemorrhage in rats. Acta Neurochir (Wien) 147:187–193

    Article  CAS  Google Scholar 

  49. Schievink WI (1997) Intracranial aneurysms. N Engl J Med 336: 28–40

    Article  PubMed  CAS  Google Scholar 

  50. Schmidt JM, Rincon F, Fernandez A, Resor C, Kowalski RG, Claassen J, Connolly ES, Fitzsimmons BF, Mayer SA (2007) Cerebral infarction associated with acute subarachnoid hemorrhage. Neurocrit Care 7: 10–17

    Article  PubMed  Google Scholar 

  51. Scozzafava J, Brindley PG, Mehta V, Findlay JM (2007) Decom-pressive bifrontal craniectomy for malignant intracranial pressure following anterior communicating artery aneurysm rupture: two case reports. Neurocrit Care 6: 49–53

    Article  PubMed  Google Scholar 

  52. Sehba FA, Mostafa G, Knopman J, Friedrich V Jr, Bederson JB (2004) Acute alterations in microvascular basal lamina after sub-arachnoid hemorrhage. J Neurosurg 101: 633–640

    PubMed  Google Scholar 

  53. Shigeno T, Fritschka E, Brock M, Schramm J, Shigeno S, Cervos-Navarro J (1982) Cerebral edema following experimental subarachnoid hemorrhage. Stroke 13: 368–379

    PubMed  CAS  Google Scholar 

  54. Sudlow CL, Warlow CP (1997) Comparable studies of the incidence of stroke and its pathological types: results from an international collaboration. International Stroke Incidence Collaboration. Stroke 28: 491–499

    PubMed  CAS  Google Scholar 

  55. Trabold B, Rothoerl R, Wittmann S, Woertgen C, Fröhlich D (2005) Cerebrospinal fluid and neutrophil respiratory burst after subarachnoid hemorrhage. Neuroimmunomodulation 12: 152–156

    Article  PubMed  CAS  Google Scholar 

  56. Tseng MY, Czosnyka M, Richards H, Pickard JD, Kirkpatrick PJ (2005) Effects of acute treatment with pravastatin on cerebral vasospasm, autoregulation, and delayed ischemic deficits after aneurysmal subarachnoid hemorrhage: a phase II randomized placebo-controlled trial. Stroke 36: 1627–1632

    Article  PubMed  CAS  Google Scholar 

  57. Tseng MY, Hutchinson PJ, Czosnyka M, Richards H, Pickard JD, Kirkpatrick PJ (2007) Effects of acute pravastatin treatment on intensity of rescue therapy, length of inpatient stay, and 6-month outcome in patients after aneurysmal subarachnoid hemorrhage. Stroke 38: 1545–1550

    Article  PubMed  CAS  Google Scholar 

  58. Turner CP, Panter SS, Sharp FR (1999) Anti-oxidants prevent focal rat brain injury as assessed by induction of heat shock proteins (HSP70, HO-1/HSP32, HSP47) following subarachnoid injections of lysed blood. Brain Res Mol Brain Res 65: 87–102

    Article  PubMed  CAS  Google Scholar 

  59. Voldby B, Enevoldsen EM (1982) Intracranial pressure changes following aneurysm rupture. Part 1: Clinical and angiographic correlations. J Neurosurg 56: 186–196

    Article  PubMed  CAS  Google Scholar 

  60. Yatsushige H, Ostrowski RP, Tsubokawa T, Colohan A, Zhang JH (2007) Role of c-Jun N-terminal kinase in early brain injury after subarachnoid hemorrhage. J Neurosci Res 85: 1436–1448

    Article  PubMed  CAS  Google Scholar 

  61. Zhang Z, Chopp M (2002) Vascular endothelial growth factor and angiopoietins in focal cerebral ischemia. Trends Cardiovasc Med 12: 62–66

    Article  PubMed  CAS  Google Scholar 

  62. Zhang ZG, Zhang L, Jiang Q, Zhang R, Davies K, Powers C, Bruggen N, Chopp M (2000) VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain. J Clin Invest 106: 829–838

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer-Verlag

About this paper

Cite this paper

Ayer, R.E., Zhang, J.H. (2008). The clinical significance of acute brain injury in subarachnoid hemorrhage and opportunity for intervention. In: Zhou, LF., et al. Cerebral Hemorrhage. Acta Neurochirurgica Supplementum, vol 105. Springer, Vienna. https://doi.org/10.1007/978-3-211-09469-3_35

Download citation

  • DOI: https://doi.org/10.1007/978-3-211-09469-3_35

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-09468-6

  • Online ISBN: 978-3-211-09469-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics