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The Non-human Primate Model of Cerebral Vasospasm

  • R. Loch Macdonald
Chapter
Part of the Springer Series in Translational Stroke Research book series (SSTSR)

Abstract

Cerebral vasospasm classically refers to narrowing of the large subarachnoid cerebral arteries occurring 3–14 days after blood clots are deposited in the subarachnoid space after subarachnoid hemorrhage (SAH) from any cause. It is most common after aneurysmal SAH because this process deposits the most dense and voluminous blood in the subarachnoid space and it is this blood clot that causes vasospasm. It is recommended that cerebral vasospasm be called angiographic vasospasm and to use this term to refer to the angiographic appearance of the cerebral arteries. The clinical consequences of angiographic vasospasm should be referred to as delayed cerebral ischemia (DCI). DCI is an important cause of morbidity and mortality after SAH and is usually associated with severe angiographic vasospasm. Animal models of angiographic vasospasm have been developed because of the difficulties modeling delayed vasospasm in vitro. These models use one of three techniques to simulate SAH: (1) an intracranial artery is punctured allowing blood to surround the artery; (2) an artery is surgically exposed and clotted autologous blood obtained from another site is placed around the artery; or (3) autologous blood from another site is injected into the subarachnoid space and allowed to surround the intracranial arteries. Each technique has advantages and disadvantages. In this chapter, we discuss the advantages and disadvantages of and methods for creation of SAH and angiographic vasospasm in non-human primates. Arterial diameters are easily quantified by angiography and SAH is created by frontal craniectomy, exposure of the intracranial arteries of the anterior circle of Willis and placement of autologous clotted blood around these arteries.

Keywords

Angiographic vasospasm Cerebral angiography Non-human primate Subarachnoid hemorrhage 

References

  1. 1.
    Fujii M, Yan J, Rolland WB, Soejima Y, Caner B, Zhang JH. Early brain injury, an evolving frontier in subarachnoid hemorrhage research. Transl Stroke Res. 2013;4:432–46.CrossRefGoogle Scholar
  2. 2.
    Macdonald RL. Delayed neurological deterioration after subarachnoid haemorrhage. Nat Rev Neurol. 2014;10:44–58.CrossRefGoogle Scholar
  3. 3.
    Dreier JP. The role of spreading depression, spreading depolarization and spreading ischemia in neurological disease. Nat Med. 2011;17:439–47.CrossRefGoogle Scholar
  4. 4.
    Stein SC, Browne KD, Chen XH, Smith DH, Graham DI. Thromboembolism and delayed cerebral ischemia after subarachnoid hemorrhage: an autopsy study. Neurosurgery. 2006;59:781–7.CrossRefGoogle Scholar
  5. 5.
    Budohoski KP, Czosnyka M, Kirkpatrick PJ, Smielewski P, Steiner LA, Pickard JD. Clinical relevance of cerebral autoregulation following subarachnoid haemorrhage. Nat Rev Neurol. 2013;9:152–63.CrossRefGoogle Scholar
  6. 6.
    Ostergaard L, Aamand R, Karabegovic S, et al. The role of the microcirculation in delayed cerebral ischemia and chronic degenerative changes after subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2013;33:1825–37.CrossRefGoogle Scholar
  7. 7.
    Zoerle T, Ilodigwe DC, Wan H, et al. Pharmacologic reduction of angiographic vasospasm in experimental subarachnoid hemorrhage: systematic review and meta-analysis. J Cereb Blood Flow Metab. 2012;32:1645–58.CrossRefGoogle Scholar
  8. 8.
    Yagi K, Lidington D, Wan H, et al. Therapeutically targeting tumor necrosis factor-alpha/sphingosine-1-phosphate signaling corrects myogenic reactivity in subarachnoid hemorrhage. Stroke. 2015;46:2260–70.CrossRefGoogle Scholar
  9. 9.
    Motterlini R, Gonzales A, Foresti R, Clark JE, Green CJ, Winslow RM. Heme oxygenase-1-derived carbon monoxide contributes to the suppression of acute hypertensive responses in vivo. Circ Res. 1998;83:568–77.CrossRefGoogle Scholar
  10. 10.
    Edvinsson L, Povlsen GK. Late cerebral ischaemia after subarachnoid haemorrhage: is cerebrovascular receptor upregulation the mechanism behind? Acta Physiol (Oxf). 2011;203:209–24.CrossRefGoogle Scholar
  11. 11.
    Sakadzic S, Lee J, Boas DA, Ayata C. High-resolution in vivo optical imaging of stroke injury and repair. Brain Res. 2015;1623:174–92.CrossRefGoogle Scholar
  12. 12.
    Macdonald RL, Weir B. Cerebral vasospasm, vol. 2001. San Diego: Academic; 2001.Google Scholar
  13. 13.
    Marbacher S, Fandino J, Kitchen ND. Standard intracranial in vivo animal models of delayed cerebral vasospasm. Br J Neurosurg. 2010;24:415–34.CrossRefGoogle Scholar
  14. 14.
    Schuller K, Buhler D, Plesnila N. A murine model of subarachnoid hemorrhage. J Vis Exp. 2013;(81):e50845.Google Scholar
  15. 15.
    Veelken JA, Laing RJ, Jakubowski J. The sheffield model of subarachnoid hemorrhage in rats. Stroke. 1995;26:1279–83.CrossRefGoogle Scholar
  16. 16.
    Bederson JB, Germano IM, Guarino L. Cortical blood flow and cerebral perfusion pressure in a new noncraniotomy model of subarachnoid hemorrhage in the rat. Stroke. 1995;26:1086–91.CrossRefGoogle Scholar
  17. 17.
    Megyesi JF, Vollrath B, Cook DA, Findlay JM. In vivo animal models of cerebral vasospasm: a review. Neurosurgery. 2000;46:448–60.CrossRefGoogle Scholar
  18. 18.
    Weir B, Erasmo R, Miller J, McIntyre J, Secord D, Mielke B. Vasospasm in response to repeated subarachnoid hemorrhages in the monkey. J Neurosurg. 1970;33:395–406.CrossRefGoogle Scholar
  19. 19.
    Espinosa F, Weir B, Shnitka T, Overton T, Boisvert D. A randomized placebo-controlled double-blind trial of nimodipine after SAH in monkeys. Part 2: pathological findings. J Neurosurg. 1984;60:1176–85.CrossRefGoogle Scholar
  20. 20.
    Fathi AR, Bakhtian KD, Marbacher S, Fandino J, Pluta RM. Blood clot placement model of subarachnoid hemorrhage in non-human primates. Acta Neurochir Suppl. 2015;120:343–6.PubMedGoogle Scholar
  21. 21.
    Pluta RM, Bacher J, Skopets B, Hoffmann V. A non-human primate model of aneurismal subarachnoid hemorrhage (SAH). Transl Stroke Res. 2014;5:681–91.CrossRefGoogle Scholar
  22. 22.
    Titova E, Ostrowski RP, Zhang JH, Tang J. Experimental models of subarachnoid hemorrhage for studies of cerebral vasospasm. Neurol Res. 2009;31:568–81.CrossRefGoogle Scholar
  23. 23.
    Macdonald RL, Zhang J, Sima B, Johns L. Papaverine-sensitive vasospasm and arterial contractility and compliance after subarachnoid hemorrhage in dogs. Neurosurgery. 1995;37:962–7.CrossRefGoogle Scholar
  24. 24.
    Rothberg CS, Weir B, Overton TR. Treatment of subarachnoid hemorrhage with sodium nitroprusside and phenylephrine: an experimental study. Neurosurgery. 1979;5:588–95.CrossRefGoogle Scholar
  25. 25.
    Espinosa F, Weir B, Overton T, Castor W, Grace M, Boisvert D. A randomized placebo-controlled double-blind trial of nimodipine after SAH in monkeys. Part 1: clinical and radiological findings. J Neurosurg. 1984;60:1167–75.CrossRefGoogle Scholar
  26. 26.
    Steinke DE, Weir BK, Findlay JM, Tanabe T, Grace M, Krushelnycky BW. A trial of the 21-aminosteroid u74006f in a primate model of chronic cerebral vasospasm. Neurosurgery. 1989;24:179–86.CrossRefGoogle Scholar
  27. 27.
    Findlay JM, Weir BK, Gordon P, Grace M, Baughman R. Safety and efficacy of intrathecal thrombolytic therapy in a primate model of cerebral vasospasm. Neurosurgery. 1989;24:491–8.CrossRefGoogle Scholar
  28. 28.
    Fathi AR, Pluta RM, Bakhtian KD, Qi M, Lonser RR. Reversal of cerebral vasospasm via intravenous sodium nitrite after subarachnoid hemorrhage in primates. J Neurosurg. 2011;115:1213–20.CrossRefGoogle Scholar
  29. 29.
    Hino A, Weir BK, Macdonald RL, Thisted RA, Kim CJ, Johns LM. Prospective, randomized, double-blind trial of bq-123 and bosentan for prevention of vasospasm following subarachnoid hemorrhage in monkeys. J Neurosurg. 1995;83:503–9.CrossRefGoogle Scholar
  30. 30.
    Findlay JM, Kassell NF, Weir BK, et al. A randomized trial of intraoperative, intracisternal tissue plasminogen activator for the prevention of vasospasm. Neurosurgery. 1995;37:168–76.CrossRefGoogle Scholar
  31. 31.
    Macdonald RL, Kakarieka A, Mayer SA, et al. Prevention of cerebral vasospasm after aneurysmal subarachnoid hemorrhage with clazosentan, an endothelin receptor antagonist. Neurosurgery. 2006;59:453. (Abstract).CrossRefGoogle Scholar
  32. 32.
    Oldfield EH, Loomba JJ, Monteith SJ, et al. Safety and pharmacokinetics of sodium nitrite in patients with subarachnoid hemorrhage: a phase IIa study. J Neurosurg. 2013;119:634–41.CrossRefGoogle Scholar
  33. 33.
    Fisher M, Feuerstein G, Howells DW, et al. Update of the stroke therapy academic industry roundtable preclinical recommendations. Stroke. 2009;40:2244–50.CrossRefGoogle Scholar
  34. 34.
    Sasaki E. Prospects for genetically modified non-human primate models, including the common marmoset. Neurosci Res. 2015;93:110–5.CrossRefGoogle Scholar
  35. 35.
    van der Worp HB, Howells DW, Sena ES, et al. Can animal models of disease reliably inform human studies? PLoS Med. 2010;7:e1000245.CrossRefGoogle Scholar
  36. 36.
    Capitanio JP, Emborg ME. Contributions of non-human primates to neuroscience research. Lancet. 2008;371:1126–35.CrossRefGoogle Scholar
  37. 37.
    (STAIR) TSTAIRT. Recommendations for standards regarding preclinical neuroprotective and restorative drug development. Stroke. 1999;30:2752–8.CrossRefGoogle Scholar
  38. 38.
    Eberle R, Hilliard J. The simian herpesviruses. Infect Agents Dis. 1995;4:55–70.PubMedGoogle Scholar
  39. 39.
    DeMarcus TA, Tipple MA, Ostrowski SR. Us policy for disease control among imported nonhuman primates. J Infect Dis. 1999;179(Suppl 1):S281–S2.CrossRefGoogle Scholar
  40. 40.
    Sughrue ME, Mocco J, Mack WJ, et al. Bioethical considerations in translational research: primate stroke. Am J Bioeth. 2009;9:3–12.CrossRefGoogle Scholar
  41. 41.
    Lapchak PA, Zhang JH, Noble-Haeusslein LJ. Rigor guidelines: escalating stair and steps for effective translational research. Transl Stroke Res. 2013;4:279–85.CrossRefGoogle Scholar
  42. 42.
    Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG. Animal research: reporting in vivo experiments—the arrive guidelines. J Cereb Blood Flow Metab. 2011;31:991–3.CrossRefGoogle Scholar
  43. 43.
    Zhang X, Hintze TH. Camp signal transduction cascade, a novel pathway for the regulation of endothelial nitric oxide production in coronary blood vessels. Arterioscler Thromb Vasc Biol. 2001;21:797–803.CrossRefGoogle Scholar
  44. 44.
    Macdonald RL, Curry DJ, Aihara Y, Zhang ZD, Jahromi BS, Yassari R. Magnesium and experimental vasospasm. J Neurosurg. 2004;100:106–10.CrossRefGoogle Scholar
  45. 45.
    Elisevich K, Cunningham IA, Assis L. Size estimation and magnification error in radiographic imaging: implications for classification of arteriovenous malformations. AJNR Am J Neuroradiol. 1995;16:531–8.PubMedGoogle Scholar
  46. 46.
    Macdonald RL, Zhang J, Marton LS, Weir B. Effects of cell-permeant calcium chelators on contractility in monkey basilar artery. J Neurotrauma. 1999;16:37–47.CrossRefGoogle Scholar
  47. 47.
    Hino A, Tokuyama Y, Kobayashi M, et al. Increased expression of endothelin B receptor mRNA following subarachnoid hemorrhage in monkeys. J Cereb Blood Flow Metab. 1996;16:688–97.CrossRefGoogle Scholar
  48. 48.
    Aihara Y, Jahromi BS, Yassari R, Sayama T, Macdonald RL. Effects of a nitric oxide donor on and correlation of changes in cyclic nucleotide levels with experimental vasospasm. Neurosurgery. 2003;52:661–7.CrossRefGoogle Scholar
  49. 49.
    Ono S, Zhang ZD, Marton LS, et al. Heme oxygenase-1 and ferritin are increased in cerebral arteries after subarachnoid hemorrhage in monkeys. J Cereb Blood Flow Metab. 2000;20:1066–76.CrossRefGoogle Scholar
  50. 50.
    Macdonald RL, Weir BK, Grace MG, Martin TP, Doi M, Cook DA. Morphometric analysis of monkey cerebral arteries exposed in vivo to whole blood, oxyhemoglobin, methemoglobin, and bilirubin. Blood Vessels. 1991;28:498–510.PubMedGoogle Scholar
  51. 51.
    Cook DJ, Kan S, Ai J, Kasuya H, Macdonald RL. Cisternal sustained release dihydropyridines for subarachnoid hemorrhage. Curr Neurovasc Res. 2012;9:139–48.CrossRefGoogle Scholar
  52. 52.
    Macdonald RL, Zhang ZD, Curry D, et al. Intracisternal sodium nitroprusside fails to prevent vasospasm in nonhuman primates. Neurosurgery. 2002;51:761–8.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • R. Loch Macdonald
    • 1
    • 2
    • 3
  1. 1.Division of NeurosurgerySt. Michael’s HospitalTorontoCanada
  2. 2.Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre for Biomedical ScienceLi Ka Shing Knowledge Institute, St. Michael’s HospitalTorontoCanada
  3. 3.Department of SurgeryUniversity of TorontoTorontoCanada

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