Skip to main content
SpringerLink
Log in
Book cover

Vascular Mechanisms in CNS Trauma pp 255–267Cite as

SAH Models: Review, New Modification, and Prospective

  • Chapter
  • First Online:

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR,volume 5))

Abstract

Subarachnoid hemorrhage (SAH) is a devastating type of hemorrhagic stroke. It is characterized by spontaneous or traumatic bleeding in the subarachnoid space and is associated with a high rate of morbidity and mortality. A reproducible animal model of SAH that mimics the acute and delayed brain injury history after SAH will be an invaluable tool for exploring the underlying mechanisms of SAH-induced brain injury and evaluating potential therapeutic interventions. At present, a number of models have been developed, mainly the double injection model and the endovascular puncture model. While different species have been studied, rodents have become the most popular and widely utilized animal subjects. In this summary, we will explore in detail the various models and animal species. We will also introduce the emerging modified model, which was recently developed within the past 5 years, and discuss the prospective study.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
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

Learn about institutional subscriptions

References

  1. Ingall T, Asplund K, Mahonen M, Bonita R (2000) A multinational comparison of subarachnoid hemorrhage epidemiology in the WHO MONICA stroke study. Stroke 31:1054–1061

    Article  PubMed  CAS  Google Scholar 

  2. Venti M (2012) Subarachnoid and intraventricular hemorrhage. Front Neurol Neurosci 30:149–153

    Article  PubMed  Google Scholar 

  3. Connolly ES Jr, Rabinstein AA, Carhuapoma JR, Derdeyn CP, Dion J, Higashida RT, Hoh BL, Kirkness CJ, Naidech AM, Ogilvy CS, Patel AB, Thompson BG, Vespa P (2012) Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 43:1711–1737

    Article  PubMed  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

    Article  PubMed  CAS  Google Scholar 

  5. Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, Vajkoczy P, Wanke I, Bach D, Frey A, Marr A, Roux S, Kassell N (2011) Clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid haemorrhage undergoing surgical clipping: a randomised, double-blind, placebo-controlled phase 3 trial (CONSCIOUS-2). Lancet Neurol 10:618–625

    Article  PubMed  CAS  Google Scholar 

  6. Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, Vajkoczy P, Wanke I, Bach D, Frey A, Nowbakht P, Roux S, Kassell N (2012) Randomized trial of clazosentan in patients with aneurysmal subarachnoid hemorrhage undergoing endovascular coiling. Stroke 43:1463–1469

    Article  PubMed  CAS  Google Scholar 

  7. 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 

  8. 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 

  9. Crompton MR (1964) The pathogenesis of cerebral infarction following the rupture of cerebral berry aneurysms. Brain 87:491–510

    Article  PubMed  CAS  Google Scholar 

  10. Megyesi JF, Vollrath B, Cook DA, Findlay JM (2000) In vivo animal models of cerebral vasospasm: a review. Neurosurgery 46:448–460, discussion 460–441

    Article  PubMed  CAS  Google Scholar 

  11. Sehba FA, Bederson JB (2006) Mechanisms of acute brain injury after subarachnoid hemorrhage. Neurol Res 28:381–398

    Article  PubMed  CAS  Google Scholar 

  12. Marbacher S, Fandino J, Kitchen ND (2010) Standard intracranial in vivo animal models of delayed cerebral vasospasm. Br J Neurosurg 24:415–434

    Article  PubMed  Google Scholar 

  13. Brawley BW, Strandness DE Jr, Kelly WA (1968) The biphasic response of cerebral vasospasm in experimental subarachnoid hemorrhage. J Neurosurg 28:1–8

    Article  PubMed  CAS  Google Scholar 

  14. Nagai H, Suzuki Y, Sugiura M, Noda S, Mabe H (1974) Experimental cerebral vasospasm. 1: Factors contributing to early spasm. J Neurosurg 41:285–292

    Article  PubMed  CAS  Google Scholar 

  15. Asano T, Sano K (1977) Pathogenetic role of no-reflow phenomenon in experimental subarachnoid hemorrhage in dogs. J Neurosurg 46:454–466

    Article  PubMed  CAS  Google Scholar 

  16. Barry KJ, Gogjian MA, Stein BM (1979) Small animal model for investigation of subarachnoid hemorrhage and cerebral vasospasm. Stroke 10:538–541

    Article  PubMed  CAS  Google Scholar 

  17. Kader A, Krauss WE, Onesti ST, Elliott JP, Solomon RA (1990) Chronic cerebral blood flow changes following experimental subarachnoid hemorrhage in rats. Stroke 21:577–581

    Article  PubMed  CAS  Google Scholar 

  18. Bederson JB, Germano IM, Guarino L (1995) Cortical blood flow and cerebral perfusion pressure in a new noncraniotomy model of subarachnoid hemorrhage in the rat. Stroke 26:1086–1091, discussion 1091–1082

    Article  PubMed  CAS  Google Scholar 

  19. Veelken JA, Laing RJ, Jakubowski J (1995) The Sheffield model of subarachnoid hemorrhage in rats. Stroke 26:1279–1283, discussion 1284

    Article  PubMed  CAS  Google Scholar 

  20. Bederson JB, Levy AL, Ding WH, Kahn R, DiPerna CA, Jenkins AL III, Vallabhajosyula P (1998) Acute vasoconstriction after subarachnoid hemorrhage. Neurosurgery 42:352–360, discussion 360–352

    Article  PubMed  CAS  Google Scholar 

  21. Sugawara T, Ayer R, Jadhav V, Chen W, Tsubokawa T, Zhang JH (2008) Simvastatin attenuation of cerebral vasospasm after subarachnoid hemorrhage in rats via increased phosphorylation of Akt and endothelial nitric oxide synthase. J Neurosci Res 86:3635–3643

    Article  PubMed  CAS  Google Scholar 

  22. Prunell GF, Mathiesen T, Svendgaard NA (2004) Experimental subarachnoid hemorrhage: cerebral blood flow and brain metabolism during the acute phase in three different models in the rat. Neurosurgery 54:426–436, discussion 436–427

    Article  PubMed  Google Scholar 

  23. Alkan T, Tureyen K, Ulutas M, Kahveci N, Goren B, Korfali E, Ozluk K (2001) Acute and delayed vasoconstriction after subarachnoid hemorrhage: local cerebral blood flow, histopathology, and morphology in the rat basilar artery. Arch Physiol Biochem 109:145–153

    Article  PubMed  CAS  Google Scholar 

  24. Park IS, Meno JR, Witt CE, Suttle TK, Chowdhary A, Nguyen TS, Ngai AC, Britz GW (2008) Subarachnoid hemorrhage model in the rat: modification of the endovascular filament model. J Neurosci Methods 172:195–200

    Article  PubMed  Google Scholar 

  25. Schwartz AY, Masago A, Sehba FA, Bederson JB (2000) Experimental models of subarachnoid hemorrhage in the rat: a refinement of the endovascular filament model. J Neurosci Methods 96:161–167

    Article  PubMed  CAS  Google Scholar 

  26. Kamii H, Kato I, Kinouchi H, Chan PH, Epstein CJ, Akabane A, Okamoto H, Yoshimoto T (1999) Amelioration of vasospasm after subarachnoid hemorrhage in transgenic mice overexpressing CuZn-superoxide dismutase. Stroke 30:867–871, discussion 872

    Article  PubMed  CAS  Google Scholar 

  27. Altay O, Hasegawa Y, Sherchan P, Suzuki H, Khatibi NH, Tang J, Zhang JH (2012) Isoflurane delays the development of early brain injury after subarachnoid hemorrhage through sphingosine-related pathway activation in mice. Crit Care Med 40:1908–1913

    Article  PubMed  CAS  Google Scholar 

  28. Altay O, Suzuki H, Hasegawa Y, Caner B, Krafft PR, Fujii M, Tang J, Zhang JH (2012) Isoflurane attenuates blood–brain barrier disruption in ipsilateral hemisphere after subarachnoid hemorrhage in mice. Stroke 43:2513–2516

    Article  PubMed  CAS  Google Scholar 

  29. Simeone FA, Ryan KG, Cotter JR (1968) Prolonged experimental cerebral vasospasm. J Neurosurg 29:357–366

    Article  PubMed  CAS  Google Scholar 

  30. Simeone FA, Trepper PJ, Brown DJ (1972) Cerebral blood flow evaluation of prolonged experimental vasospasm. J Neurosurg 37:302–311

    Article  PubMed  CAS  Google Scholar 

  31. Schwartz AY, Sehba FA, Bederson JB (2000) Decreased nitric oxide availability contributes to acute cerebral ischemia after subarachnoid hemorrhage. Neurosurgery 47:208–214, discussion 214–205

    PubMed  CAS  Google Scholar 

  32. Lougheed WM, Tom M (1961) A method of introducing blood into the subarachnoid space in the region of the circle of Willis in dogs. Can J Surg 4:329–337

    PubMed  CAS  Google Scholar 

  33. McQueen JD, Jeanes LD (1964) Dehydration and rehydration of the brain with hypertonic urea and mannitol. J Neurosurg 21:118–128

    Article  PubMed  CAS  Google Scholar 

  34. McQueen JD, Jelsma LF (1967) Intracranial hypertension. Cerebrospinal fluid pressure rises following intracisternal infusions of blood components in dogs. Arch Neurol 16:501–508

    Article  PubMed  CAS  Google Scholar 

  35. Martins AN, Doyle TF, Newby N, Kobrine AI, Ramirez A (1975) The effect of a simulated subarachnoid hemorrhage on cerebral blood flow in the monkey. Stroke 6:664–672

    Article  PubMed  CAS  Google Scholar 

  36. Prunell GF, Mathiesen T, Svendgaard NA (2002) A new experimental model in rats for study of the pathophysiology of subarachnoid hemorrhage. Neuroreport 13:2553–2556

    Article  PubMed  Google Scholar 

  37. 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

    Article  PubMed  CAS  Google Scholar 

  38. Peters ND, Di Chiro G (1976) A model for spasm of the anterior cerebral artery. Stroke 7:243–247

    Article  PubMed  CAS  Google Scholar 

  39. Chow RW, Newton TH, Smith MC, Adams JE (1968) Cerebral vasospasm induced by subarachnoid blood and serotonin. An angiographic study. Invest Radiol 3:402–407

    Article  PubMed  CAS  Google Scholar 

  40. Echlin FA (1965) Spasm of basilar and vertebral arteries caused by experimental subarachnoid hemorrhage. J Neurosurg 23:1–11

    Article  PubMed  CAS  Google Scholar 

  41. Matz PG, Fujimura M, Lewen A, Morita-Fujimura Y, Chan PH (2001) Increased cytochrome c-mediated DNA fragmentation and cell death in manganese-superoxide dismutase-deficient mice after exposure to subarachnoid hemolysate. Stroke 32:506–515

    Article  PubMed  CAS  Google Scholar 

  42. Peerless SJ, Fox AJ, Komatsu K, Hunter IG (1982) Angiographic study of vasospasm following subarachnoid hemorrhage in monkeys. Stroke 13:473–479

    Article  PubMed  CAS  Google Scholar 

  43. Delgado-Zygmunt TJ, Arbab MA, Shiokawa Y, Svendgaard NA (1992) A primate model for acute and late cerebral vasospasm: angiographic findings. Acta Neurochir 118:130–136

    Article  PubMed  CAS  Google Scholar 

  44. Varsos VG, Liszczak TM, Han DH, Kistler JP, Vielma J, Black PM, Heros RC, Zervas NT (1983) Delayed cerebral vasospasm is not reversible by aminophylline, nifedipine, or papaverine in a “two-hemorrhage” canine model. J Neurosurg 58:11–17

    Article  PubMed  CAS  Google Scholar 

  45. Prunell GF, Mathiesen T, Diemer NH, Svendgaard NA (2003) Experimental subarachnoid hemorrhage: subarachnoid blood volume, mortality rate, neuronal death, cerebral blood flow, and perfusion pressure in three different rat models. Neurosurgery 52:165–175, discussion 175–166

    PubMed  Google Scholar 

  46. Lee JY, Huang DL, Keep R, Sagher O (2008) Characterization of an improved double hemorrhage rat model for the study of delayed cerebral vasospasm. J Neurosci Methods 168:358–366

    Article  PubMed  Google Scholar 

  47. Krafft PR, Bailey EL, Lekic T, Rolland WB, Altay O, Tang J, Wardlaw JM, Zhang JH, Sudlow CL (2012) Etiology of stroke and choice of models. Int J Stroke 7:398–406

    Article  PubMed  Google Scholar 

  48. Clark JF, Sharp FR (2006) Bilirubin oxidation products (boxes) and their role in cerebral vasospasm after subarachnoid hemorrhage. J Cereb Blood Flow Metab 26:1223–1233

    Article  PubMed  CAS  Google Scholar 

  49. Pyne GJ, Cadoux-Hudson TA, Clark JF (2001) Cerebrospinal fluid from subarachnoid haemorrhage patients causes excessive oxidative metabolism compared to vascular smooth muscle force generation. Acta Neurochir 143:59–62, discussion 62–53

    Article  PubMed  CAS  Google Scholar 

  50. Zhao W, Ujiie H, Tamano Y, Akimoto K, Hori T, Takakura K (1999) Sudden death in a rat subarachnoid hemorrhage model. Neurol Med Chir (Tokyo) 39:735–741, discussion 741–733

    Article  CAS  Google Scholar 

  51. Marbacher S, Andereggen L, Neuschmelting V, Widmer HR, von Gunten M, Takala J, Jakob SM, Fandino J (2012) A new rabbit model for the study of early brain injury after subarachnoid hemorrhage. J Neurosci Methods 208:138–145

    Article  PubMed  Google Scholar 

  52. Marbacher S, Sherif C, Neuschmelting V, Schlappi JA, Takala J, Jakob SM, Fandino J (2010) Extra-intracranial blood shunt mimicking aneurysm rupture: Intracranial-pressure-controlled rabbit subarachnoid hemorrhage model. J Neurosci Methods 191:227–233

    Article  PubMed  Google Scholar 

  53. Munoz-Sanchez MA, Egea-Guerrero JJ, Revuelto-Rey J, Moreno-Valladares M, Murillo-Cabezas F (2012) A new percutaneous model of subarachnoid haemorrhage in rats. J Neurosci Methods 211:88–93

    Article  PubMed  CAS  Google Scholar 

  54. Simard JM, Tosun C, Ivanova S, Kurland DB, Hong C, Radecki L, Gisriel C, Mehta R, Schreibman D, Gerzanich V (2012) Heparin reduces neuroinflammation and transsynaptic neuronal apoptosis in a model of subarachnoid hemorrhage. Transl Stroke Res 3:155–165

    Article  PubMed  CAS  Google Scholar 

  55. Dusick JR, Evans BC, Laiwalla A, Krahl S, Gonzalez NR (2011) A minimally-invasive rat model of subarachnoid hemorrhage and delayed ischemic injury. Surg Neurol Int 2:99

    Article  PubMed  Google Scholar 

  56. Lin CL, Calisaneller T, Ukita N, Dumont AS, Kassell NF, Lee KS (2003) A murine model of subarachnoid hemorrhage-induced cerebral vasospasm. J Neurosci Methods 123:89–97

    Article  PubMed  Google Scholar 

  57. Altay T, Smithason S, Volokh N, Rasmussen PA, Ransohoff RM, Provencio JJ (2009) A novel method for subarachnoid hemorrhage to induce vasospasm in mice. J Neurosci Methods 183:136–140

    Article  PubMed  Google Scholar 

  58. Solomon RA, Antunes JL, Chen RY, Bland L, Chien S (1985) Decrease in cerebral blood flow in rats after experimental subarachnoid hemorrhage: a new animal model. Stroke 16:58–64

    Article  PubMed  CAS  Google Scholar 

  59. Zhang JH, Badaut J, Tang J, Obenaus A, Hartman R, Pearce WJ (2012) The vascular neural network-a new paradigm in stroke pathophysiology. Nat Rev Neurol 8:711–716

    Article  PubMed  CAS  Google Scholar 

  60. Germanwala AV, Huang J, Tamargo RJ (2010) Hydrocephalus after aneurysmal subarachnoid hemorrhage. Neurosurg Clin N Am 21:263–270

    Article  PubMed  Google Scholar 

  61. Wang YM, Lin YJ, Chuang MJ, Lee TH, Tsai NW, Cheng BC, Lin WC, Su BY, Yang TM, Chang WN, Huang CC, Kung CT, Lee LH, Wang HC, Lu CH (2012) Predictors and outcomes of shunt-dependent hydrocephalus in patients with aneurysmal sub-arachnoid hemorrhage. BMC Surg 12:12

    Article  PubMed  Google Scholar 

  62. Kagerbauer SM, Rothoerl RD, Brawanski A (2007) Pituitary dysfunction after aneurysmal subarachnoid hemorrhage. Neurol Res 29:283–288

    Article  PubMed  CAS  Google Scholar 

  63. Suda N, Moriyama K, Ganburged G (2013) Effect of angiotensin II receptor blocker on experimental periodontitis in a mouse model of Marfan syndrome. Infect Immun 81(1):182–188

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology and Pharmacology, School of Medicine, Loma Linda University, Loma Linda, CA, 92354, USA

    John H. Zhang

  2. Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA

    Sheng Chen, Damon Klebe, Alexander Vakhmyanin & Mutsumi Fujii

Authors
  1. Sheng Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Damon Klebe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexander Vakhmyanin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mutsumi Fujii
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. John H. Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John H. Zhang .

Editor information

Editors and Affiliations

  1. Departments of Neurology and Radiology, Massachusetts General Hospital Harvard Medical School, Boston, Massachusetts, USA

    Eng H. Lo

  2. Department of Pediatrics, Massachusetts General Hospital Harvard Medical School, Boston, Massachusetts, USA

    Josephine Lok

  3. Department of Neurology, Massachusetts General Hospital Harvard Medical School, Boston, Massachusetts, USA

    MingMing Ning

  4. Department of Pediatrics, Massachusetts General Hospital Harbard Medical School, Boston, Massachusetts, USA

    Michael J. Whalen

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Chen, S., Klebe, D., Vakhmyanin, A., Fujii, M., Zhang, J.H. (2014). SAH Models: Review, New Modification, and Prospective. In: Lo, E., Lok, J., Ning, M., Whalen, M. (eds) Vascular Mechanisms in CNS Trauma. Springer Series in Translational Stroke Research, vol 5. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8690-9_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-8690-9_14

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-8689-3

  • Online ISBN: 978-1-4614-8690-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation