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Inflammation in Subarachnoid Hemorrhage and Delayed Deterioration Associated with Vasospasm: A Review

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Cerebral Vasospasm: Neurovascular Events After Subarachnoid Hemorrhage

Part of the book series: Acta Neurochirurgica Supplement ((NEUROCHIRURGICA,volume 115))

Abstract

Delayed deterioration associated with vasospasm (DDAV) after subarachnoid hemorrhage (SAH), (often called vasospasm) continues to be both a difficult entity to treat and a leading cause of morbidity in patients. Until recently, attention was focused on alleviating the vascular spasm. Recent evidence shows that vascular spasm may not account for all the morbidity of DDAV. There is renewed interest in looking for other potential targets for therapy. Inflammation has become a promising area of research for new treatments. This review explores the evidence that inflammation is a driver of DDAV by asking three questions: (1) If inflammation is important in the pathogenesis of the disease, what part or parts of the inflammatory response are involved? (2) When does inflammation occur in SAH? (3) In what compartment of the skull does the inflammation occur, the cerebrospinal fluid and meninges, the cerebral arteries, or the brain itself?

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References

  1. Bianchi ME (2007) DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 81:1–5

    Article  PubMed  CAS  Google Scholar 

  2. Chaichana KL, Levy AP, Miller-Lotan R, Shakur S, Tamargo RJ (2007) Haptoglobin 2–2 genotype determines chronic vasospasm after experimental subarachnoid hemorrhage. Stroke 38:3266–3271

    Article  PubMed  CAS  Google Scholar 

  3. Clark JF, Reilly M, Sharp FR (2002) Oxidation of bilirubin produces compounds that cause prolonged vasospasm of rat cerebral vessels: a contributor to subarachnoid hemorrhage-induced vasospasm. J Cereb Blood Flow Metab 22:472–478

    Article  PubMed  CAS  Google Scholar 

  4. 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 

  5. Clatterbuck RE, Gailloud P, Ogata L, Gebremariam A, Dietsch GN, Murphy KJ, Tamargo RJ (2003) Prevention of cerebral vasospasm by a humanized anti-CD11/CD18 monoclonal antibody administered after experimental subarachnoid hemorrhage in nonhuman primates. J Neurosurg 99:376–382

    Article  PubMed  CAS  Google Scholar 

  6. Clatterbuck RE, Oshiro EM, Hoffman PA, Dietsch GN, Pardoll DM, Tamargo RJ (2002) Inhibition of vasospasm with lymphocyte function-associated antigen-1 monoclonal antibody in a femoral artery model in rats. J Neurosurg 97:676–682

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  8. Delves PJ, Roitt IM (2000) The immune system. N Engl J Med 343:37–49

    Article  PubMed  CAS  Google Scholar 

  9. Eiserich JP, Baldus S, Brennan ML, Ma W, Zhang C, Tousson A, Castro L, Lusis AJ, Nauseef WM, White CR, Freeman BA (2002) Myeloperoxidase, a leukocyte-derived vascular NO oxidase. Science 296:2391–2394

    Article  PubMed  CAS  Google Scholar 

  10. Etminan N, Vergouwen MD, Ilodigwe D, Macdonald RL (2011) Effect of pharmaceutical treatment on vasospasm, delayed cerebral ischemia, and clinical outcome in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. J Cereb Blood Flow Metab 31:1443–1451

    Article  PubMed  CAS  Google Scholar 

  11. Eugenin EA, Eckardt D, Theis M, Willecke K, Bennett MV, Saez JC (2001) Microglia at brain stab wounds express connexin 43 and in vitro form functional gap junctions after treatment with interferon-gamma and tumor necrosis factor-alpha. Proc Natl Acad Sci USA 98:4190–4195

    Article  PubMed  CAS  Google Scholar 

  12. Fassbender K, Schneider S, Bertsch T, Schlueter D, Fatar M, Ragoschke A, Kuhl S, Kischka U, Hennerici M (2000) Temporal profile of release of interleukin-1beta in neurotrauma. Neurosci Lett 284:135–138

    Article  PubMed  CAS  Google Scholar 

  13. Gaetani P, Tartara F, Pignatti P, Tancioni F, Rodriguez y Baena R, De Benedetti F (1998) Cisternal CSF levels of cytokines after subarachnoid hemorrhage. Neurol Res 20:337–342

    PubMed  CAS  Google Scholar 

  14. Gallia GL, Tamargo RJ (2006) Leukocyte-endothelial cell interactions in chronic vasospasm after subarachnoid hemorrhage. Neurol Res 28:750–758

    Article  PubMed  CAS  Google Scholar 

  15. Gao J, Wang H, Sheng H, Lynch JR, Warner DS, Durham L, Vitek MP, Laskowitz DT (2006) A novel apoE-derived therapeutic reduces vasospasm and improves outcome in a murine model of subarachnoid hemorrhage. Neurocrit Care 4:25–31

    Article  PubMed  CAS  Google Scholar 

  16. Gentleman SM, Leclercq PD, Moyes L, Graham DI, Smith C, Griffin WST, Nicoll JAR (2004) Long-term intracerebral inflammatory response after traumatic brain injury. Forensic Sci Int 146:97–104

    Article  PubMed  CAS  Google Scholar 

  17. Haley EC Jr, Kassell NF, Torner JC, Truskowski LL, Germanson TP (1994) A randomized trial of two doses of nicardipine in aneurysmal subarachnoid hemorrhage. A report of the Cooperative Aneurysm Study. J Neurosurg 80:788–796

    Article  PubMed  Google Scholar 

  18. Handa Y, Kabuto M, Kobayashi H, Kawano H, Takeuchi H, Hayashi M (1991) The correlation between immunological reaction in the arterial wall and the time course of the development of cerebral vasospasm in a primate model. Neurosurgery 28:542–549

    Article  PubMed  CAS  Google Scholar 

  19. Hansen-Schwartz J (2004) Cerebral vasospasm: a consideration of the various cellular mechanisms involved in the pathophysiology. Neurocrit Care 1:235–246

    Article  PubMed  CAS  Google Scholar 

  20. Hansen-Schwartz J, Vajkoczy P, Macdonald RL, Pluta RM, Zhang JH (2007) Cerebral vasospasm: looking beyond vasoconstriction. Trends Pharmacol Sci 28:252–256

    Article  PubMed  CAS  Google Scholar 

  21. Hendryk S, Jarzab B, Josko J (2004) Increase of the IL-1 beta and IL-6 levels in CSF in patients with vasospasm following aneurysmal SAH. Neuroendocrinol Lett 25:141–147

    PubMed  CAS  Google Scholar 

  22. Hughes JT, Schianchi PM (1978) Cerebral artery spasm. A histological study at necropsy of the blood vessels in cases of subarachnoid hemorrhage. J Neurosurg 48:515–525

    Article  PubMed  CAS  Google Scholar 

  23. Iuliano BA, Pluta RM, Jung C, Oldfield EH (2004) Endothelial dysfunction in a primate model of cerebral vasospasm. J Neurosurg 100:287–294

    Article  PubMed  Google Scholar 

  24. Khurana VG, Fox DJ, Meissner I, Meyer FB, Spetzler RF (2006) Update on evidence for a genetic predisposition to cerebral vasospasm. Neurosurg Focus 21:E3

    Article  PubMed  Google Scholar 

  25. Kikuchi T, Okuda Y, Kaito N, Abe T (1995) Cytokine production in cerebrospinal fluid after subarachnoid haemorrhage. Neurol Res 17:106–108

    PubMed  CAS  Google Scholar 

  26. Kwan AL, Solenski NJ, Kassell NF, Lee KS (1997) Inhibition of nitric oxide generation and lipid peroxidation attenuates hemolysate-induced injury to cerebrovascular endothelium. Acta Neurochir (Wien) 139:240–247

    Article  CAS  Google Scholar 

  27. Ma CX, Yin WN, Cai BW, Wu J, Wang JY, He M, Sun H, Ding JL, You C (2009) Toll-like receptor 4/nuclear factor-kappa B signaling detected in brain after early subarachnoid hemorrhage. Chin Med J (Engl) 122:1575–1581

    CAS  Google Scholar 

  28. Macdonald RL, Kassell NF, Mayer S, Ruefenacht D, Schmiedek P, Weidauer S, Frey A, Roux S, Pasqualin A, CONSCIOUS-1 Investigators (2008) Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1): randomized, double-blind, placebo-controlled phase 2 dose-finding trial. Stroke 39:3015–3021

    Article  PubMed  CAS  Google Scholar 

  29. Maiuri F, Gallicchio B, Donati P, Carandente M (1987) The blood leukocyte count and its prognostic significance in subarachnoid hemorrhage. J Neurosurg Sci 31:45–48

    PubMed  CAS  Google Scholar 

  30. McGirt MJ, Lynch JR, Blessing R, Warner DS, Friedman AH, Laskowitz DT (2002) Serum von Willebrand factor, matrix metalloproteinase-9, and vascular endothelial growth factor levels predict the onset of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Neurosurgery 51:1128–1134

    Article  PubMed  Google Scholar 

  31. McGirt MJ, Mavropoulos JC, McGirt LY, Alexander MJ, Friedman AH, Laskowitz DT, Lynch JR (2003) Leukocytosis as an independent risk factor for cerebral vasospasm following aneurysmal subarachnoid hemorrhage. J Neurosurg 98:1222–1226

    Article  PubMed  Google Scholar 

  32. Mesis RG, Wang H, Lombard FW, Yates R, Vitek MP, Borel CO, Warner DS, Laskowitz DT (2006) Dissociation between vasospasm and functional improvement in a murine model of subarachnoid hemorrhage. Neurosurg Focus 21:E4

    Article  PubMed  Google Scholar 

  33. Minami N, Tani E, Yokota M, Maeda Y, Yamaura I (1991) Immunohistochemistry of leukotriene C4 in experimental cerebral vasospasm. Acta Neuropathol 81:401–407

    Article  PubMed  CAS  Google Scholar 

  34. Nam DH, Kim JS, Hong SC, Lee WH, Lee JI, Shin HJ, Park K, Eoh W, Han DH, Kim JH (2001) Expression of interleukin-1 beta in lipopolysaccharide stimulated monocytes derived from patients with aneurysmal subarachnoid hemorrhage is correlated with cerebral vasospasm. Neurosci Lett 312:41–44

    Article  PubMed  CAS  Google Scholar 

  35. Neil-Dwyer G, Cruickshank J (1974) The blood leucocyte count and its prognostic significance in subarachnoid haemorrhage. Brain 97:79–86

    Article  PubMed  CAS  Google Scholar 

  36. Ng WH, Moochhala S, Yeo TT, Ong PL, Ng PY (2001) Nitric oxide and subarachnoid hemorrhage: elevated level in cerebrospinal fluid and their implications. Neurosurgery 49:622–626

    PubMed  CAS  Google Scholar 

  37. Niikawa S, Hara S, Ohe N, Miwa Y, Ohkuma A (1997) Correlation between blood parameters and symptomatic vasospasm in subarachnoid hemorrhage patients. Neurol Med Chir 37:881–884

    Article  CAS  Google Scholar 

  38. 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 142:83–90

    Article  CAS  Google Scholar 

  39. Pellettieri L, Carlson CA, Lindholm L (1981) Is the vasospasm following subarachnoidal hemorrhage an immunoreactive disease? Experientia 37:1170–1171

    Article  PubMed  CAS  Google Scholar 

  40. Pluta RM, Oldfield EH (2006) Sodium nitrite as a therapeutic agent for central nervous system diseases. Surg Neurol 66:5–7

    Article  PubMed  Google Scholar 

  41. Pluta RM, Thompson BG, Afshar JK, Boock RJ, Iuliano B, Oldfield EH (2001) Nitric oxide and vasospasm. Acta Neurochir Suppl 77:67–72

    PubMed  CAS  Google Scholar 

  42. Pluta RM, Zauner A, Morgan JK, Muraszko KM, Oldfield EH (1992) Is vasospasm related to proliferative arteriopathy? J Neurosurg 77:740–748

    Article  PubMed  CAS  Google Scholar 

  43. Polin RS, Bavbek M, Shaffrey ME, Billups K, Bogaev CA, Kassell NF, Lee KS (1998) Detection of soluble E-selectin, ICAM-1, VCAM-1, and L-selectin in the cerebrospinal fluid of patients after subarachnoid hemorrhage. J Neurosurg 89:559–567

    Article  PubMed  CAS  Google Scholar 

  44. Pradilla G, Thai QA, Legnani FG, Hsu W, Kretzer RM, Wang PP, Tamargo RJ (2004) Delayed intracranial delivery of a nitric oxide donor from a controlled-release polymer prevents experimental cerebral vasospasm in rabbits. Neurosurgery 55:1393–1399

    Article  PubMed  Google Scholar 

  45. Provencio JJ, Altay T, Smithason S, Moore SK, Ransohoff RM (2011) Depletion of Ly6G/C(+) cells ameliorates delayed cerebral vasospasm in subarachnoid hemorrhage. J Neuroimmunol 232:94–100

    Article  PubMed  CAS  Google Scholar 

  46. Provencio JJ, Fu X, Siu A, Rasmussen PA, Hazen SL, Ransohoff RM (2010) CSF neutrophils are implicated in the development of vasospasm in subarachnoid hemorrhage. Neurocrit Care 12:244–251

    Article  PubMed  CAS  Google Scholar 

  47. Pyne-Geithman GJ, Morgan CJ, Wagner K, Dulaney EM, Carrozzella J, Kanter DS, Zuccarello M, Clark JF (2005) Bilirubin production and oxidation in CSF of patients with cerebral vasospasm after subarachnoid hemorrhage. J Cereb Blood Flow Metab 25:1070–1077

    Article  PubMed  CAS  Google Scholar 

  48. Roy A, Rozanov C, Mokashi A, Daudu P, Al-mehdi AB, Shams H, Lahiri S (2000) Mice lacking in gp91 phox subunit of NAD(P)H oxidase showed glomus cell [Ca(2+)](i) and respiratory responses to hypoxia. Brain Res 872:188–193

    Article  PubMed  CAS  Google Scholar 

  49. Sabri M, Ai J, Macdonald RL (2011) Nitric oxide related pathophysiological changes following subarachnoid haemorrhage. Acta Neurochir Suppl 110:105–109

    Article  PubMed  Google Scholar 

  50. Sehba FA, Pluta RM, Zhang JH (2011) Metamorphosis of subarachnoid hemorrhage research: from delayed vasospasm to early brain injury. Mol Neurobiol 43:27–40

    Article  PubMed  CAS  Google Scholar 

  51. Sela S, Shurtz-Swirski R, Awad J, Shapiro G, Nasser L, Shasha SM, Kristal B (2002) The involvement of peripheral polymorphonuclear leukocytes in the oxidative stress and inflammation among cigarette smokers. Isr Med Assoc J 4:1015–1019

    PubMed  Google Scholar 

  52. Stein SC, Levine JM, Nagpal S, LeRoux PD (2006) Vasospasm as the sole cause of cerebral ischemia: how strong is the evidence? Neurosurg Focus 21:E2

    Article  PubMed  Google Scholar 

  53. Tekkok IH, Tekkok S, Ozcan OE, Erbengi T, Erbengi A (1994) Preventive effect of intracisternal heparin for proliferative angiopathy after experimental subarachnoid haemorrhage in rats. Acta Neurochir (Wien) 127:112–117

    Article  CAS  Google Scholar 

  54. Vieweg U, Schramm J, Urbach H (1999) Platelet-derived growth factor (PDGF-AB) like immune reactivity in serum and in cerebral spinal fluid following experimental subarachnoid haemorrhage in dogs. Acta Neurochir 141:861–865

    Article  CAS  Google Scholar 

  55. Wang L, Shi JX, Yin HX, Ma CY, Zhang QR (2005) The influence of subarachnoid hemorrhage on neurons: an animal model. Ann Clin Lab Sci 35:79–85

    PubMed  Google Scholar 

  56. Yamaguchi M, Zhou C, Nanda A, Zhang JH (2004) Ras protein contributes to cerebral vasospasm in a canine double-hemorrhage model. Stroke 35:1750–1755

    Article  PubMed  CAS  Google Scholar 

  57. Yang MF, Sun BL, Xia ZL, Zhu LZ, Qiu PM, Zhang SM (2003) Alleviation of brain edema by L-arginine following experimental subarachnoid hemorrhage in a rat model. Clin Hemorheol Microcirc 29:437–443

    PubMed  CAS  Google Scholar 

  58. Yatsushige H, Yamaguchi M, Zhou C, Calvert JW, Zhang JH, Yatsushige H, Yamaguchi M, Zhou C, Calvert JW, Zhang JH (2005) Role of c-Jun N-terminal kinase in cerebral vasospasm after experimental subarachnoid hemorrhage. Stroke 36:1538–1543

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

I would like to acknowledge David Schumick for developing the illustration.

Financial Disclosure

This work was supported by a grant from the National Institutes of Health (K08-NS051350 J.J.P.) and the Cleveland Clinic Cerebrovascular Center (Institutional Support J.J.P.).

Conflicts of Interest Statement

I declare that I have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurology, Neuroinflammation Research and Cerebrovascular Centers, Cleveland Clinic, NC30, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    J. Javier Provencio M.D.

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  1. J. Javier Provencio M.D.
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Correspondence to J. Javier Provencio M.D. .

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Editors and Affiliations

  1. , Department of Neurosurgery, University of Cincinnati, Stetson, Suite 2200 260, Cincinnati, 45267-0515, Ohio, USA

    Mario Zuccarello

  2. College of Medicine, Department of Neurology, University of Cincinnati, Albert Sabin Way 231MSB room 1, Cincinnati, 46267-0536, Ohio, USA

    Joseph F. Clark

  3. College of Medicine, Dept. of Neurology and Neurosurgery, University of Cincinnati, Albert Sabin Way 231ML0517, Cincinnati, 45267-0517, Ohio, USA

    Gail Pyne-Geithman

  4. College of Medicine, Dept. of Neurosurgery, University of Cincinnati, Stetson St. Suite 260ML0515, Cincinnati, 45219, Ohio, USA

    Norberto Andaluz

  5. College of Medicine, Dept. of Neurosurgery, University of Cincinnati, Stetson, Suite 2200 260, Cincinnati, 45219, Ohio, USA

    Jed A. Hartings

  6. , Dept. of Emergency Medicine, University of Cincinnati, Albert Sabin Way 231ML0769, Cincinnati, 45267-0769, Ohio, USA

    Opeolu M. Adeoye

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Provencio, J.J. (2013). Inflammation in Subarachnoid Hemorrhage and Delayed Deterioration Associated with Vasospasm: A Review. In: Zuccarello, M., Clark, J., Pyne-Geithman, G., Andaluz, N., Hartings, J., Adeoye, O. (eds) Cerebral Vasospasm: Neurovascular Events After Subarachnoid Hemorrhage. Acta Neurochirurgica Supplement, vol 115. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1192-5_42

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  • DOI: https://doi.org/10.1007/978-3-7091-1192-5_42

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