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Neurology Research International
Volume 2013 (2013), Article ID 972417, 11 pages
http://dx.doi.org/10.1155/2013/972417
Review Article

Nitric Oxide in Cerebral Vasospasm: Theories, Measurement, and Treatment

1Vanderbilt University, School of Medicine, 121 Medical Center Drive, Nashville, TN 37232, USA
2Department of Neurological Surgery, Vanderbilt University, School of Medicine, Medical Center Drive, Nashville, TN 37232, USA

Received 7 November 2012; Revised 23 May 2013; Accepted 28 May 2013

Academic Editor: Jeff Bronstein

Copyright © 2013 Michael Siuta et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. N. F. Kassell, T. Sasaki, A. R. T. Colohan, and G. Nazar, “Cerebral vasospasm following aneurysmal subarachnoid hemorrhage,” Stroke, vol. 16, no. 4, pp. 562–572, 1985. View at Scopus
  2. J. Hansen-Schwartz, P. Vajkoczy, R. L. Macdonald, R. M. Pluta, and J. H. Zhang, “Cerebral vasospasm: looking beyond vasoconstriction,” Trends in Pharmacological Sciences, vol. 28, no. 6, pp. 252–256, 2007. View at Publisher · View at Google Scholar · View at Scopus
  3. R. M. Pluta, J. H. Zhang, J. Hansen-Schwartz et al., “Cerebral vasospasm following subarachnoid hemorrhage: time for a new world of thought,” Neurological Research, vol. 31, no. 2, pp. 151–158, 2009. View at Publisher · View at Google Scholar · View at Scopus
  4. R. M. Pluta, “Delayed cerebral vasospasm and nitric oxide: review, new hypothesis, and proposed treatment,” Pharmacology & Therapeutics, vol. 105, no. 1, pp. 23–56, 2005. View at Publisher · View at Google Scholar · View at Scopus
  5. G. J. Velat, M. M. Kimball, J. D. Mocco, and B. L. Hoh, “Vasospasm after aneurysmal subarachnoid hemorrhage: review of randomized controlled trials and meta-analyses in the literature,” World Neurosurgery, vol. 76, no. 5, pp. 446–454, 2011. View at Publisher · View at Google Scholar · View at Scopus
  6. J. P. Dreier, C. Drenckhahn, J. Woitzik, et al., “Spreading ischemia after aneurysmal subarachnoid hemorrhage,” Acta Neurochirurgica, vol. 115, pp. 125–129, 2013.
  7. S. Nishizawa, “The roles of early brain injury in cerebral vasospasm following subarachnoid hemorrhage: from clinical and scientific aspects,” Acta Neurochirurgica, vol. 115, pp. 207–211, 2013.
  8. T. Sasaki and Y. Kikkawa, “Proposed mechanism of cerebral vasospasm: our hypothesis and current topics,” Acta Neurochirurgica, vol. 115, pp. 53–56, 2013.
  9. M. K. Winkler, Y. Chassidim, S. Lublinsky, et al., “Impaired neurovascular coupling to ictal epileptic activity and spreading depolarization in a patient with subarachnoid hemorrhage: possible link to blood-brain barrier dysfunction,” Epilepsia, vol. 53, supplement 6, pp. 22–30, 2012.
  10. U. Förstermann and T. Münzel, “Endothelial nitric oxide synthase in vascular disease,” Circulation, vol. 113, no. 13, pp. 1708–1714, 2006. View at Publisher · View at Google Scholar
  11. M. Sabri, J. Ai, B. Knight et al., “Uncoupling of endothelial nitric oxide synthase after experimental subarachnoid hemorrhage,” Journal of Cerebral Blood Flow and Metabolism, vol. 31, no. 1, pp. 190–199, 2011. View at Publisher · View at Google Scholar · View at Scopus
  12. L. Edvinsson and D. N. Krause, Cerebral Blood Flow and Metabolism, Lippincott Williams & Wilkins, Philadelphia, Pa, USA, 2nd edition, 2002.
  13. C. Nathan and Q.-W. Xie, “Nitric oxide synthases: roles, tolls, and controls,” Cell, vol. 78, no. 6, pp. 915–918, 1994. View at Publisher · View at Google Scholar · View at Scopus
  14. S. Milstien and Z. Katusic, “Oxidation of tetrahydrobiopterin by peroxynitrite: implications for vascular endothelial function,” Biochemical and Biophysical Research Communications, vol. 263, no. 3, pp. 681–684, 1999. View at Publisher · View at Google Scholar · View at Scopus
  15. S. M. Morris Jr. and T. R. Billiar, “New insights into the regulation of inducible nitric oxide synthesis,” American Journal of Physiology, vol. 266, no. 6, pp. E829–E839, 1994. View at Scopus
  16. R. M. Pluta, B. G. Thompson, T. M. Dawson, S. H. Snyder, R. J. Boock, and E. H. Oldfield, “Loss of nitric oxide synthase immunoreactivity in cerebral vasospasm,” Journal of Neurosurgery, vol. 84, no. 4, pp. 648–654, 1996. View at Scopus
  17. K. Cosby, K. S. Partovi, J. H. Crawford et al., “Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation,” Nature Medicine, vol. 9, no. 12, pp. 1498–1505, 2003. View at Publisher · View at Google Scholar · View at Scopus
  18. A. R. Fathi, R. M. Pluta, K. D. Bakhtian, M. Qi, and R. R. Lonser, “Reversal of cerebral vasospasm via intravenous sodium nitrite after subarachnoid hemorrhage in primates: laboratory investigation,” Journal of Neurosurgery, vol. 115, no. 6, pp. 1213–1220, 2011. View at Publisher · View at Google Scholar · View at Scopus
  19. R. M. Pluta, E. H. Oldfield, K. D. Bakhtian et al., “Safety and feasibility of long-term intravenous sodium nitrite infusion in healthy volunteers,” PLoS ONE, vol. 6, no. 1, Article ID e14504, 2011. View at Publisher · View at Google Scholar · View at Scopus
  20. R. M. Pluta, A. Dejam, G. Grimes, M. T. Gladwin, and E. H. Oldfield, “Nitrite infusions to prevent delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage,” Journal of the American Medical Association, vol. 293, no. 12, pp. 1477–1484, 2005. View at Publisher · View at Google Scholar · View at Scopus
  21. R. E. Ayer and J. H. Zhang, “Oxidative stress in subarachnoid haemorrhage: significance in acute brain injury and vasospasm,” Acta Neurochirurgica, vol. 104, pp. 33–41, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. F. Marzatico, P. Gaetani, V. Silvani, D. Lombardi, E. Sinforiani, and R. Baena, “Experimental isobaric subarachnoid hemorrhage: regional mitochondrial function during the acute and late phase,” Surgical Neurology, vol. 34, no. 5, pp. 294–300, 1990. View at Publisher · View at Google Scholar · View at Scopus
  23. R. Rodriguez y Baena, P. Gaetani, V. Silvani, G. Spanu, and F. Marzatico, “Effect of nimodipine on mitochondrial respiration in different rat brain areas after subarachnoid haemorrhage,” Acta Neurochirurgica, vol. 43, pp. 177–181, 1988. View at Scopus
  24. F. Marzatico, P. Gaetani, R. Rodriguez y Baena, V. Silvani, P. Paoletti, and G. Benzi, “Bioenergetics of different brain areas after experimental subarachnoid hemorrhage in rats,” Stroke, vol. 19, no. 3, pp. 378–384, 1988. View at Scopus
  25. K. Rejdak, A. Petzold, M. A. Sharpe et al., “Cerebrospinal fluid nitrite/nitrate correlated with oxyhemoglobin and outcome in patients with subarachnoid hemorrhage,” Journal of the Neurological Sciences, vol. 219, no. 1-2, pp. 71–76, 2004. View at Publisher · View at Google Scholar · View at Scopus
  26. K. Takenaka, N. F. Kassell, P. L. Foley, K. S. Lee, and J. J. Marshall, “Oxyhemoglobin-induced cytotoxicity and arachidonic acid release in cultured bovine endothelial cells,” Stroke, vol. 24, no. 6, pp. 839–845, 1993. View at Scopus
  27. J. M. C. Gutteridge, “Iron promoters of the Fenton reaction and lipid peroxidation can be released from haemoglobin by peroxides,” FEBS Letters, vol. 201, no. 2, pp. 291–295, 1986. View at Scopus
  28. H. P. Misra and I. Fridovich, “The generation of superoxide radical during the autoxidation of hemoglobin,” The Journal of Biological Chemistry, vol. 247, no. 21, pp. 6960–6962, 1972. View at Scopus
  29. P. J. Kuhlencordt, R. Gyurko, F. Han et al., “Accelerated atherosclerosis, aortic aneurysm formation, and ischemic heart disease in apolipoprotein E/endothelial nitric oxide synthase double-knockout mice,” Circulation, vol. 104, no. 4, pp. 448–454, 2001. View at Scopus
  30. A. S. Dumont, R. J. Dumont, M. M. Chow et al., “Cerebral vasospasm after subarachnoid hemorrhage: putative role of inflammation,” Neurosurgery, vol. 53, no. 1, pp. 123–135, 2003. View at Scopus
  31. M. Kurzelewski, E. Czarnowska, and A. Berȩsewicz, “Superoxide- and nitric oxide-derived species mediate endothelial dysfunction, endothelial glycocalyx disruption, and enhanced neutrophil adhesion in the post-ischemic guinea-pig heart,” Journal of Physiology and Pharmacology, vol. 56, no. 2, pp. 163–178, 2005. View at Scopus
  32. F. A. Sehba and J. B. Bederson, “Nitric oxide in early brain injury after subarachnoid hemorrhage,” Acta Neurochirurgica, vol. 110, part 1, pp. 99–103, 2011. View at Scopus
  33. F. A. Sehba, A. Y. Schwartz, I. Chereshnev, and J. B. Bederson, “Acute decrease in cerebral nitric oxide levels after subarachnoid hemorrhage,” Journal of Cerebral Blood Flow and Metabolism, vol. 20, no. 3, pp. 604–611, 2000. View at Scopus
  34. W. H. Ng, S. Moochhala, T. T. Yeo, P. L. Ong, and P. Y. Ng, “Nitric oxide and subarachnoid hemorrhage: elevated levels in cerebrospinal fluid and their implications,” Neurosurgery, vol. 49, no. 3, pp. 622–627, 2001. View at Scopus
  35. A. Khaldi, A. Zauner, M. Reinert, J. J. Woodward, and M. R. Bullock, “Measurement of nitric oxide and brain tissue oxygen tension in patients after severe subarachnoid hemorrhage,” Neurosurgery, vol. 49, no. 1, pp. 33–40, 2001. View at Scopus
  36. M. Suzuki, H. Asahara, S. Endo et al., “Increased levels of nitrite/nitrate in the cerebrospinal fluid of patients with subarachnoid hemorrhage,” Neurosurgical Review, vol. 22, no. 2-3, pp. 96–98, 1999. View at Publisher · View at Google Scholar · View at Scopus
  37. C. S. Jung, E. H. Oldfield, J. Harvey-White et al., “Association of an endogenous inhibitor of nitric oxide synthase with cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage,” Journal of Neurosurgery, vol. 107, no. 5, pp. 945–950, 2007. View at Publisher · View at Google Scholar · View at Scopus
  38. A. Woszczyk, W. Deinsberger, and D. K. Böker, “Nitric oxide metabolites in cisternal CSF correlate with cerebral vasospasm in patients with a subarachnoid haemorrhage,” Acta Neurochirurgica, vol. 145, no. 4, pp. 257–264, 2003. View at Publisher · View at Google Scholar · View at Scopus
  39. A. K. Vellimana, E. Milner, T. D. Azad et al., “Endothelial nitric oxide synthase mediates endogenous protection against subarachnoid hemorrhage-induced cerebral vasospasm,” Stroke, vol. 42, no. 3, pp. 776–782, 2011. View at Publisher · View at Google Scholar · View at Scopus
  40. O. W. Sakowitz, S. Wolfrum, A. S. Sarrafzadeh, J. F. Stover, W. R. Lanksch, and A. W. Unterberg, “Temporal profiles of extracellular nitric oxide metabolites following aneurysmal subarachnoid hemorrhage,” Acta Neurochirurgica, vol. 81, pp. 351–354, 2002. View at Scopus
  41. F. Staub, R. Graf, P. Gabel, M. Köchling, N. Klug, and W.-D. Heiss, “Multiple interstitial substances measured by microdialysis in patients with subarachnoid hemorrhage,” Neurosurgery, vol. 47, no. 5, pp. 1106–1116, 2000. View at Scopus
  42. A. Khaldi, A. Zauner, M. Reinert, J. J. Woodward, and M. R. Bullock, “Measurement of nitric oxide and brain tissue oxygen tension in patients after severe subarachnoid hemorrhage,” Neurosurgery, vol. 49, no. 1, pp. 33–40, 2001. View at Scopus
  43. M. Reinert, A. Zauner, A. Khaldi, et al., “Microdialysis nitric oxide levels and brain tissue oxygen tension in patients with subarachnoid hemorrhage,” Acta Neurochirurgica, vol. 77, pp. 155–157, 2001. View at Scopus
  44. F. Staub, R. Graf, P. Gabel, M. Köchling, N. Klug, and W.-D. Heiss, “Multiple interstitial substances measured by microdialysis in patients with subarachnoid hemorrhage,” Neurosurgery, vol. 47, no. 5, pp. 1106–1116, 2000. View at Scopus
  45. R. M. Starke, G. H. Kim, R. J. Komotar et al., “Endothelial nitric oxide synthase gene single-nucleotide polymorphism predicts cerebral vasospasm after aneurysmal subarachnoid hemorrhage,” Journal of Cerebral Blood Flow and Metabolism, vol. 28, no. 6, pp. 1204–1211, 2008. View at Publisher · View at Google Scholar · View at Scopus
  46. N. U. Ko, P. Rajendran, H. Kim et al., “Endothelial nitric oxide synthase polymorphism (-786T→C) and increased risk of angiographic vasospasm after aneurysmal subarachnoid hemorrhage,” Stroke, vol. 39, no. 4, pp. 1103–1108, 2008. View at Publisher · View at Google Scholar · View at Scopus
  47. J. Claassen, G. L. Bernardini, K. Kreiter et al., “Effect of cisternal and ventricular blood on risk of delayed cerebral ischemia after subarachnoid hemorrhage,” Stroke, vol. 32, no. 9, pp. 2012–2020, 2001. View at Scopus
  48. C. D. Reiter, X. Wang, J. E. Tanus-Santos et al., “Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease,” Nature Medicine, vol. 8, no. 12, pp. 1383–1389, 2002. View at Publisher · View at Google Scholar · View at Scopus
  49. T. Tanishima, “Cerebral vasospasm: contractile activity of hemoglobin in isolated canine basilar arteries,” Journal of Neurosurgery, vol. 53, no. 6, pp. 787–793, 1980. View at Scopus
  50. D. A. Wink and J. B. Mitchell, “Chemical biology of nitric oxide: insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide,” Free Radical Biology and Medicine, vol. 25, no. 4-5, pp. 434–456, 1998. View at Publisher · View at Google Scholar · View at Scopus
  51. J. F. Clark, M. Reilly, and F. R. Sharp, “Oxidation of bilirubin produces compounds that cause prolonged vasospasm of rat cerebral vessels: a contributor to subarachnoid hemorrhage-induced vasospasm,” Journal of Cerebral Blood Flow and Metabolism, vol. 22, no. 4, pp. 472–478, 2002. View at Scopus
  52. T. S. Tierney, G. Pradilla, P. P. Wang, R. E. Clatterbuck, and R. J. Tamargo, “Intracranial delivery of the nitric oxide donor diethylenetriamine/nitric oxide from a controlled-release polymer: toxicity in cynomolgus monkeys,” Neurosurgery, vol. 58, no. 5, pp. 952–960, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. M. Sabri, J. Ai, P. A. Marsden, and R. L. Macdonald, “Simvastatin re-couples dysfunctional endothelial nitric oxide synthase in experimental subarachnoid hemorrhage,” PLoS ONE, vol. 6, no. 2, Article ID e17062, 2011. View at Publisher · View at Google Scholar · View at Scopus
  54. K. Sydow and T. Münzel, “ADMA and oxidative stress,” Atherosclerosis Supplements, vol. 4, no. 4, pp. 41–51, 2003. View at Publisher · View at Google Scholar · View at Scopus
  55. G. S. Allen, “Cerebral arterial spasm. Part 8: the treatment of delayed cerebral arterial spasm in human being,” Surgical Neurology, vol. 6, no. 2, pp. 71–80, 1976. View at Scopus
  56. J. Pachl, P. Haninec, T. Tencer et al., “The effect of subarachnoid sodium nitroprusside on the prevention of vasospasm in subarachnoid haemorrhage,” Acta Neurochirurgica, no. 95, pp. 141–145, 2005. View at Publisher · View at Google Scholar · View at Scopus
  57. J. E. Thomas and G. McGinnis, “Safety of intraventricular sodium nitroprusside and thiosulfate for the treatment of cerebral vasospasm in the intensive care unit setting,” Stroke, vol. 33, no. 2, pp. 486–492, 2002. View at Publisher · View at Google Scholar · View at Scopus
  58. R. Kumar, A. Pathak, S. N. Mathuriya, and N. Khandelwal, “Intraventricular sodium nitroprusside therapy: a future promise for refractory subarachnoid hemorrhage-induced vasospasm,” Neurology India, vol. 51, no. 2, pp. 197–202, 2003. View at Scopus
  59. A. Raabe, H. Vatter, M. Zimmermann, and V. Seifert, “Reversal of tissue hypoxia by a single intraventricular dose of sodium nitroprusside in a patient with severe medically refractory cerebral vasospasm after subarachnoid haemorrhage,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 72, no. 1, pp. 123–124, 2002. View at Publisher · View at Google Scholar · View at Scopus
  60. A. Raabe, M. Zimmermann, M. Setzer et al., “Effect of intraventricular sodium nitroprusside on cerebral hemodynamics and oxygenation in poor-grade aneurysm patients with severe, medically refractory vasospasm,” Neurosurgery, vol. 50, no. 5, pp. 1006–1014, 2002. View at Publisher · View at Google Scholar · View at Scopus
  61. A. Pathak, S. N. Mathuriya, N. Khandelwal, and K. Verma, “Intermittent low dose intrathecal sodium nitroprusside therapy for treatment of symptomatic aneurysmal SAH-induced vasospasm,” British Journal of Neurosurgery, vol. 17, no. 4, pp. 306–310, 2003. View at Publisher · View at Google Scholar · View at Scopus
  62. R. L. Macdonald, Z.-D. Zhang, D. Curry et al., “Intracisternal sodium nitroprusside fails to prevent vasospasm in nonhuman primates,” Neurosurgery, vol. 51, no. 3, pp. 761–770, 2002. View at Publisher · View at Google Scholar · View at Scopus
  63. K. Nakao, H. Murata, K. Kanamaru, and S. Waga, “Effects of nitroglycerin on vasospasm and cyclic nucleotides in a primate model of subarachnoid hemorrhage,” Stroke, vol. 27, no. 10, pp. 1882–1888, 1996. View at Scopus
  64. J. G. Frazee, S. L. Giannotta, and W. E. Stern, “Intravenous nitroglycerin for the treatment of chronic cerebral vasoconstriction in the primate,” Journal of Neurosurgery, vol. 55, no. 6, pp. 865–868, 1981. View at Scopus
  65. K. Kanamaru, B. K. A. Weir, J. M. Findlay, C. A. Krueger, and D. A. Cook, “Pharmacological studies on relaxation of spastic primate cerebral arteries in subarachnoid hemorrhage,” Journal of Neurosurgery, vol. 71, no. 6, pp. 909–915, 1989. View at Scopus
  66. S. R. Ramdurg, A. Suri, D. Gupta et al., “Magnetic resonance imaging evaluation of subarachnoid hemorrhage in rats and the effects of intracisternal injection of papaverine and nitroglycerine in the management of cerebral vasospasm,” Neurology India, vol. 58, no. 3, pp. 377–383, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. Y. Tanaka, T. Masuzawa, M. Saito, et al., “Combined administration of fasudil hydrochloride and nitroglycerin for treatment of cerebral vasospasm,” Acta Neurochirurgica, vol. 77, pp. 205–207, 2001. View at Scopus
  68. Y. Ito, E. Isotani, Y. Mizuno, H. Azuma, and K. Hirakawa, “Effective improvement of the cerebral vasospasm after subarachnoid hemorrhage with low-dose nitroglycerin,” Journal of Cardiovascular Pharmacology, vol. 35, no. 1, pp. 45–50, 2000. View at Publisher · View at Google Scholar · View at Scopus
  69. W. S. Lesley, A. Lazo, J. C. Chaloupka, and J. B. Weigele, “Successful treatment of cerebral vasospasm by use of transdermal nitroglycerin ointment (Nitropaste),” American Journal of Neuroradiology, vol. 24, no. 6, pp. 1234–1236, 2003. View at Scopus
  70. M. Reinert, R. Wiest, L. Barth, R. Andres, C. Ozdoba, and R. Seiler, “Transdermal nitroglycerin in patients with subarachnoid hemorrhage,” Neurological Research, vol. 26, no. 4, pp. 435–439, 2004. View at Publisher · View at Google Scholar · View at Scopus
  71. A. R. Fathi, K. D. Bakhtian, and R. M. Pluta, “The role of nitric oxide donors in treating cerebral vasospasm after subarachnoid hemorrhage,” Acta Neurochirurgica, vol. 110, part 1, pp. 93–97, 2011. View at Scopus
  72. O. M. Qahwash, A. Alaraj, V. Aletich, F. T. Charbel, and S. Amin-Hanjani, “Safety of early endovascular catheterization and intervention through extracranial-intracranial bypass grafts,” Journal of Neurosurgery, vol. 116, no. 1, pp. 201–207, 2012. View at Publisher · View at Google Scholar · View at Scopus
  73. A. R. Fathi, S. Marbacher, T. Graupner et al., “Continuous intrathecal glyceryl trinitrate prevents delayed cerebral vasospasm in the single-SAH rabbit model in vivo,” Acta Neurochirurgica, vol. 153, no. 8, pp. 1669–1675, 2011. View at Publisher · View at Google Scholar · View at Scopus
  74. E. W. Wolf, A. Banerjee, J. Soble-Smith, F. C. Dohan Jr., R. P. White, and J. T. Robertson, “Reversal of cerebral vasospasm using an intrathecally administered nitric oxide donor,” Journal of Neurosurgery, vol. 89, no. 2, pp. 279–288, 1998. View at Scopus
  75. V. Malik, V. V. Holobotovskyy, J. K. Phillips, D. J. Mckitrick, and L. F. Arnolda, “Intrathecal cGMP elicits pressor responses and maintains mean blood pressure during haemorrhage in anaesthetized rats,” The Journal of Physiology, vol. 581, no. 2, pp. 543–552, 2007. View at Publisher · View at Google Scholar · View at Scopus
  76. B. H. Han, A. K. Vellimana, M.-L. Zhou, et al., “Phosphodiesterase 5 inhibition attenuates cerebral vasospasm and improves functional recovery after experimental subarachnoid hemorrhage,” Neurosurgery, vol. 70, no. 1, pp. 178–187, 2012. View at Publisher · View at Google Scholar
  77. E. Koktekir, Y. Erdem, M. Akif Bayar, C. Gokcek, M. Karatay, and C. Kilic, “A new approach to the treatment of cerebral vasospasm: the angiographic effects of tadalafil on experimental vasospasm,” Acta Neurochirurgica, vol. 152, no. 3, pp. 463–469, 2010. View at Publisher · View at Google Scholar · View at Scopus
  78. D. S. Bredt, C. D. Ferris, and S. H. Snyder, “Nitric oxide synthase regulatory sites. Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/calmodulin protein kinase; identification of flavin and calmodulin binding sites,” The Journal of Biological Chemistry, vol. 267, no. 16, pp. 10976–10981, 1992. View at Scopus
  79. S. Dimmeler, E. Dernbach, and A. M. Zeiher, “Phosphorylation of the endothelial nitric oxide synthase at Ser-1177 is required for VEGF-induced endothelial cell migration,” FEBS Letters, vol. 477, no. 3, pp. 258–262, 2000. View at Publisher · View at Google Scholar · View at Scopus
  80. P. F. Mount, B. E. Kemp, and D. A. Power, “Regulation of endothelial and myocardial NO synthesis by multi-site eNOS phosphorylation,” Journal of Molecular and Cellular Cardiology, vol. 42, no. 2, pp. 271–279, 2007. View at Publisher · View at Google Scholar · View at Scopus
  81. M. J. McGirt, G. Pradilla, F. G. Legnani et al., “Systemic administration of simvastatin after the onset of experimental subarachnoid hemorrhage attenuates cerebral vasospasm,” Neurosurgery, vol. 58, no. 5, pp. 945–951, 2006. View at Publisher · View at Google Scholar · View at Scopus
  82. T. Sugawara, V. Jadhav, R. Ayer, and J. Zhang, “Simvastatin attenuates cerebral vasospasm and improves outcomes by upregulation of PI3K/Akt pathway in a rat model of subarachnoid hemorrhage,” Acta Neurochirurgica, vol. 102, pp. 391–394, 2008. View at Publisher · View at Google Scholar · View at Scopus
  83. M.-Y. Tseng, M. Czosnyka, H. Richards, J. D. Pickard, and P. J. Kirkpatrick, “Effects of acute treatment with pravastatin on cerebral vasospasm, autoregulation, and delayed ischemic deficits after aneurysmal subarachnoid hemorrhage,” Stroke, vol. 36, no. 8, pp. 1627–1632, 2005. View at Publisher · View at Google Scholar · View at Scopus
  84. A. H. Kramer, “Statins in the management of aneurysmal subarachnoid hemorrhage: an overview of animal research, observational studies, randomized controlled trials and meta-analyses,” Acta Neurochirurgica, vol. 110, part 2, pp. 193–201, 2011. View at Scopus
  85. M. Y. Tseng, “Summary of evidence on immediate statins therapy following aneurysmal subarachnoid hemorrhage,” Neurocritical Care, vol. 15, no. 2, pp. 298–301, 2011. View at Publisher · View at Google Scholar · View at Scopus
  86. A. H. Kramer and J. J. Fletcher, “Statins in the management of patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis,” Neurocritical Care, vol. 12, no. 2, pp. 285–296, 2010. View at Publisher · View at Google Scholar · View at Scopus
  87. A. V. R. Santhanam and Z. S. Katusic, “Erythropoietin and cerebral vascular protection: role of nitric oxide,” Acta Pharmacologica Sinica, vol. 27, no. 11, pp. 1389–1394, 2006. View at Publisher · View at Google Scholar · View at Scopus
  88. A. V. R. Santhanam, L. A. Smith, M. Akiyama, A. G. Rosales, K. R. Bailey, and Z. S. Katusic, “Role of endothelial NO synthase phosphorylation in cerebrovascular protective effect of recombinant erythropoietin during subarachnoid hemorrhage-induced cerebral vasospasm,” Stroke, vol. 36, no. 12, pp. 2731–2737, 2005. View at Publisher · View at Google Scholar · View at Scopus
  89. M. Y. Tseng, P. J. Hutchinson, H. K. Richards et al., “Acute systemic erythropoietin therapy to reduce delayed ischemic deficits following aneurysmal subarachnoid hemorrhage: a phase II randomized, double-blind, placebo-controlled trial. Clinical article,” Journal of Neurosurgery, vol. 111, no. 1, pp. 171–180, 2009. View at Publisher · View at Google Scholar · View at Scopus
  90. M. Y. Tseng, P. J. Hutchinson, and P. J. Kirkpatrick, “Interaction of neurovascular protection of erythropoietin with age, sepsis, and statin therapy following aneurysmal subarachnoid hemorrhage,” Journal of Neurosurgery, vol. 112, no. 6, pp. 1235–1239, 2010. View at Publisher · View at Google Scholar · View at Scopus
  91. J. D. Turner, A. Mammis, and C. J. Prestigiacomo, “Erythropoietin for the treatment of subarachnoid hemorrhage: a review,” World Neurosurgery, vol. 73, no. 5, pp. 500–507, 2010. View at Publisher · View at Google Scholar · View at Scopus
  92. T. A. Sullivan, E. E. Geisert, J. P. Templeton, and T. S. Rex, “Dose-dependent treatment of optic nerve crush by exogenous systemic mutant erythropoietin,” Experimental Eye Research, vol. 96, no. 1, pp. 36–41, 2012. View at Publisher · View at Google Scholar · View at Scopus
  93. Z. P. Wang, H. S. Chen, and F. X. Wang, “Influence of plasma and cerebrospinal fluid levels of endothelin-1 and No in reducing cerebral vasospasm after subarachnoid hemorrhage during treatment with mild hypothermia, in a dog model,” Cell Biochemistry and Biophysics, vol. 61, no. 1, pp. 137–143, 2011. View at Publisher · View at Google Scholar · View at Scopus
  94. K. Osuka, Y. Watanabe, M. Yasuda, and M. Takayasu, “Adiponectin activates endothelial nitric oxide synthase through AMPK signaling after subarachnoid hemorrhage,” Neuroscience Letters, vol. 514, no. 1, pp. 2–5, 2012. View at Publisher · View at Google Scholar · View at Scopus
  95. V. G. Khurana, L. A. Smith, T. A. Baker, D. Eguchi, T. O'Brien, and Z. S. Katusic, “Protective vasomotor effects of in vivo recombinant endothelial nitric oxide synthase gene expression in a canine model of cerebral vasospasm,” Stroke, vol. 33, no. 3, pp. 782–789, 2002. View at Publisher · View at Google Scholar · View at Scopus
  96. H. Onoue, M. Tsutsui, L. Smith, A. Stelter, T. O'Brien, and Z. S. Katusic, “Expression and function of recombinant endothelial nitric oxide synthase gene in canine basilar artery after experimental subarachnoid hemorrhage,” Stroke, vol. 29, no. 9, pp. 1959–1966, 1998. View at Scopus
  97. M. Stoodley, C. C. Weihl, Z.-D. Zhang et al., “Effect of adenovirus-mediated nitric oxide synthase gene transfer on vasospasm after experimental subarachnoid hemorrhage,” Neurosurgery, vol. 46, no. 5, pp. 1193–1203, 2000. View at Scopus
  98. V. G. Khurana, L. A. Smith, D. A. Weiler, et al., “Adenovirus-mediated gene transfer to human cerebral arteries,” Journal of Cerebral Blood Flow & Metabolism, vol. 20, no. 9, pp. 1360–1371, 2000. View at Publisher · View at Google Scholar
  99. M. Tsutsui, H. Onoue, Y. Iida, L. Smith, T. O'Brien, and Z. S. Katusic, “Effects of recombinant eNOS gene expression on reactivity of small cerebral arteries,” American Journal of Physiology, vol. 278, no. 2, pp. H420–H427, 2000. View at Scopus
  100. N. Egemen, R. K. Turker, U. Sanlidilek et al., “The effect of intrathecal sodium nitroprusside on severe chronic vasospasm,” Neurological Research, vol. 15, no. 5, pp. 310–315, 1993. View at Scopus
  101. L. F. Hirsh, “Intra-arterial nitroprusside treatment of acute experimental vasospasm,” Stroke, vol. 11, no. 6, pp. 601–605, 1980. View at Scopus
  102. C. S. Rothberg, B. Weir, and T. R. Overton, “Treatment of subarachnoid hemorrhage with sodium nitroprusside and phenylephrine: an experimental study,” Neurosurgery, vol. 5, no. 5, pp. 588–595, 1979. View at Scopus
  103. J. E. Thomas and R. H. Rosenwasser, “Reversal of severe cerebral vasospasm in three patients after aneurysmal subarachnoid hemorrhage: initial observations regarding the use of intraventricular sodium nitroprusside in humans,” Neurosurgery, vol. 44, no. 1, pp. 48–58, 1999. View at Publisher · View at Google Scholar · View at Scopus
  104. J. E. Thomas, R. H. Rosenwasser, R. A. Armonda, J. Harrop, W. Mitchell, and I. Galaria, “Safety of intrathecal sodium nitroprusside for the treatment and prevention of refractory cerebral vasospasm and ischemia in humans,” Stroke, vol. 30, no. 7, pp. 1409–1416, 1999. View at Scopus
  105. G. Pradilla, Q.-A. Thai, F. G. Legnani et al., “Delayed intracranial delivery of a nitric oxide donor from a controlled-release polymer prevents experimental cerebral vasospasm in rabbits,” Neurosurgery, vol. 55, no. 6, pp. 1393–1400, 2004. View at Publisher · View at Google Scholar · View at Scopus
  106. A. H. Kramer, “Statins in the management of aneurysmal subarachnoid hemorrhage—not (yet) a standard of care,” Stroke, vol. 40, no. 3, pp. e80–e82, 2009. View at Publisher · View at Google Scholar · View at Scopus