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Vol. 20, No. 6, 2005
Issue release date: November 2005

Hyperbaric Oxygen Therapy of Cerebral Ischemia

Helms A.K. · Whelan H.T. · Torbey M.T.
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Background: Hyperbaric oxygen (HBO) therapy of cerebral ischemia has been evaluated in a number of human and animal studies; however, there is presently no consensus on its efficacy. Methods: We present a review of animal and human studies on HBO therapy of cerebral ischemia as well as present potential mechanisms of action of HBO. Results: Animal studies of HBO have shown promise by reducing infarct size and improving neurologic outcome. HBO has also been shown to inhibit inflammation and apoptosis after cerebral ischemia. Early reports in humans also suggested benefit in stroke patients treated with HBO. Recent randomized, controlled human studies, however, have not shown benefit, although all were limited by small sample size. Important differences between animal and human studies suggest HBO might be more effective in stroke within the first few hours and at a pressure of 2–3 ATA. Conclusions: The clinical usefulness of HBO in the treatment of cerebral ischemia is not yet certain. Attention to emerging pathophysiologic data should be taken into consideration in design of any future clinical trials of HBO in acute ischemic stroke.

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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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  1. Nighoghossian N, Trouillas P: Hyperbaric oxygen in the treatment of acute ischemic stroke: an unsettled issue. J Neurol Sci 1997;150:27–31.
  2. The alternative therapy evaluation committee for the insurance corporation of British Columbia: a review of the scientific evidence on the treatment of traumatic brain injuries and strokes with hyperbaric oxygen. Brain Injury 2003;3:225–236.

    External Resources

  3. Kindwall EP: A history of hyperbaric medicine; in Kindwall EP, Whelan HT (eds): Hyperbaric Medicine Practice. Flagstaff, Best Publishing, 1999.
  4. Hammarlund C: The physiologic effects of hyperbaric oxygenation; in: Kindwall EP, Whelan HT (eds): Hyperbaric Medicine Practice. Flagstaff, Best Publishing, 1999.
  5. Smithe G, Lawrence DD, Renfrew S, Ledingham I, Sharp GR: Preservation of cerebral cortical activity by breathing oxygen at 2 ATA pressure during cerebral ischemia. Surg Gynecol Obstet 1961;113:13–16.
  6. Sunami K, Takeda Y, Hashimoto M, Hirakawa M: Hyperbaric oxygen reduces infarct volume in rats by increasing oxygen supply to the ischemic periphery. Crit Care Med 2000;28:2831–2836.
  7. Chang CF, Niu KC, Hoffer BJ, Wang Y, Borlongan CV: Hyperbaric oxygen therapy for treatment of postischemic stroke in adult rats. Exp Neurol 2000;166:298–306.
  8. Rosenthal RE, Silbergleit R, Hof PR, Haywood Y, Fiskum G: Hyperbaric oxygen reduces neuronal death and improves neurological outcome after canine cardiac arrest. Stroke 2003;34:1311–1316.
  9. Demchenko IT, Luchakow YI, Moskvin AN, Gutsaeva DR, Allen BW, Thalmann ED, Piantadosi CA: Cerebral blood flow and brain oxygenation in rats breathing oxygen under pressure. J Cereb Blood Flow Metab. March 23, 2005, pp 1–13 (Epub ahead of print).
  10. Yang Z, Camporesi C, Yang X, Wang J, Bosco G, Lok J, Gorji R, Schelper RL, Camporesi EM: Hyperbaric oxygenation mitigates focal cerebral injury and reduces striatal dopamine release in a rat model of transient middle cerebral artery occlusion. Eur J App Physiol 2002;87:101–107.
  11. Weinstein PR, Hameroff SR, Johnson PC, Anderson GG: Effect of hyperbaric oxygen therapy or dimethyl sulfoxide on cerebral ischemia in unanesthetized gerbils. Neurosurgery 1986;18:528–532.
  12. Kondo A, Baba S, Iwaki T, Harai H, Koga H, Kimura T, Takmatsu J: Hyperbaric oxygenation prevents delayed neuronal death following transient ischaemia in the gerbil hippocampus. Neuropath Appl Neurobiol 1996;22:350–360.
  13. Yin D, Zhou C, Kusaka I, Calvert JW, Parent AD, Nanda A, Zhang JH: Inhibition of apoptosis by hyperbaric oxygen in a rat focal cerebral ischemic model. J Cereb Blood Flow Metab 2003;23:855–864.
  14. Veltkamp R, Siebing DA, Heiland S, Schoenffeldt-Varas P, Veltkamp C, Schwaninger M, Schwab S: Hyperbaric oxygen induces rapid protection against focal cerebral ischemia. Brain Res 2005;1037:134–138.
  15. Calvert JW, Yin W, Patel M, Badr A, Mychaskiw G, Parent AD, Zhang JH: Hyperbaric oxygenation prevented brain injury induced by hypoxia-ischemia in a neonatal rat model. Brain Res 2002;951:1–8.
  16. Atochin DN, Fisher D, Demchenko IT, Thom SR: Neutrophil sequestration and the effect of hyperbaric oxygen in a rat model of temporary middle cerebral artery occlusion. Undersea Hyperb Med 2000;27:185–190.
  17. Miljkovic-Lolic M, Silbergleit R, Fiskum G, Rosenthal RE: Neuroprotective effects of hyperbaric oxygen treatment in experimental focal cerebral ischemia are associated with reduced brain leukocyte myeloperoxidase activity. Brain Res 2003;971:90–94.
  18. Wada K, Ito M, Miyazawa T, Katoh H, Nawashiro H, Shima K, Chigasaki H: Repeated hyperbaric oxygen induces ischemic tolerance in gerbil hippocampus. Brain Res 1996;740:15–20.
  19. Wada K, Miyazawa T, Nomura N, Nawashiro H, Shima K: Preferential conditions for and possible mechanisms of induction of ischemic tolerance by repeated hyperbaric oxygenation in gerbil hippocampus. Neurosurgery 2001;49:160–167.
  20. Dong H, Xiong L, Zhu Z, Chen S, Hou L, Sakabe T: Preconditioning with hyperbaric oxygen and hyperoxia induces tolerance against spinal cord ischemia in rabbits. Anesthesiology 2002;96:907–912.
  21. Wada K, Kiyazawa T, Nomura N, Yano A, Tsuzuki N, Nawashiro H, Shima K: Mn-SOD and Bcl-2 expression after repeated hyperbaric oxygenation. Acta Neurochir Suppl 2000;76:285–290.
  22. Ostrowski RP, Colohan ART, Zhang JH: Mechanisms of hyperbaric oxygen-induces neuroprotection in a rat model of subarachnoid hemorrhage. J Cereb Blood Flow Metab 2005;25:554–571.
  23. Mink RB, Dutka AJ: Hyperbaric oxygen after global cerebral ischemia in rabbits reduces brain vascular permeability and blood flow. Stroke 1995;26:2307–2312.
  24. Jean W, Spellman SR, Nussbaum ES, Low WC: Reperfusion injury after focal cerebral ischemia: the role of inflammation and the therapeutic horizon. Neurosurgery 1998;43:1382–1396.
  25. Kataoka H, Kim S-W, Plasnila N: Leukocyte-endothelium interactions during permanent focal cerebral ischemia in mice. J Cereb Blood Flow Metab 2004;24:668–676.
  26. Pozzilli C, Lenzi GL, Argentino C, Bozzao L, Rasura M, Giubilei F, Fieschi C: Peripheral white blood cell count in cerebral ischemic infarction. Acta Neurol Scand 1985;71:396–400.
  27. Zhang Rl, Chopp M, Jiang N, Tang WX, Prostak J, Manning AM, Anderson DC: Anti-intercellular adhesion molecule-1 antibody reduces ischemic cell damage after transient but not permanent middle cerebral artery occlusion in the wistar rat. Stroke 1995;26:1438–1443.
  28. Matsuo Y, Onodera H, Shiga Y, Nakamura M, Ninomiya M, Kihara T, Kogure K: Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion. Stroke 1994;25:1469–1475.
  29. Bowes M, Zivin J, Tothlein R: Monoclonal antibody to the ICAM-1 adhesion site reduces neurological damage in a rabbit cerebral embolism stroke model. Exp Neurol 1993;119:215–219.
  30. Chopp M, Zhang R, Chen H, Li Y, Jiang N, Rusche JR: Postischemic administration of an anti-Mac-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in rats. Stroke 1994;25:869–876.
  31. Chopp M, Li Y, Jiang N, Zhang RL, Prostak J: Antibodies against adhesion molecules reduce apoptosis after transient middle cerebral artery occlusion in rat brain. J Cereb Blood Flow Metab 1996;16:578–584.
  32. Buras JA, Stahl GL, Svoboda KH, Reenstra WR: Hyperbaric oxygen downregulates ICAM-1 expression induced by hypoxia and hypoglycemia: the role of NOS. Am J Physiol Cell Physiol 2000;278:C292–C302.
  33. Bayati S, Russell RC, Roth AC: Stimulation of angiogenesis to improve the viability of prefabricated flaps. Plast Reconstruct Surg 1998;101:1290–1295.
  34. Zhao LL, Davidson JB, Wee SC, Rothe SI, Mustoe TA: Effect of hyperbaric oxygen and growth factors on rabbit ear ischemic ulcers. Arch Surg 1994;139:1043–1049.

    External Resources

  35. Chuba PJ, Aronin P, Bhambhani K, Eichenhorn M, Zamarano L, Cianci P, Muhlbauer M, Porter AT, Fontanesi J: Hyperbaric oxygen therapy for radiation-induced brain injury in children. Cancer 1997;80:2005–2012.
  36. Kohshi K, Imada H, Nomoto S, Yamaguchi R, Abe H, Yamamoto H: Successful treatment of radiation-induced brain necrosis by hyperbaric oxygen therapy. J Neurol Sci 2003;209:115–117.
  37. Omae T, Ibayashi S, Kusuda K, Nakamura H, Yagi H, Fujishima M: Effects of high atmospheric pressure and oxygen on middle cerebral blood flow velocity in humans measured by transcranial doppler. Stroke 1998;29:94–97.
  38. Zhilyaev SY, Moskvin AN, Platonova TF, Gutsaeva DR, Churilina IV, Demchenko IT: Hyperoxic vasoconstriction in the brain is mediated by inactivation of nitric oxide by superoxide anions. Neurosci Behav Phys 2003;33:783–787.
  39. Sukoff MH, Ragatz RE: Hyperbaric oxygenation for the treatment of acute cerebral edema. Neurosurgery 1982;10:29–38.
  40. Rockswold SB, Rockswold GL, Vargo JM, Erickson CA, Sutton RL, Bergman TA, Biros MH: Effects of hyperbaric oxygenation therapy on cerebral metabolism and intracranial pressure in severely brain injured patients. J Neurosurg 2001;95:544–546.
  41. Kindwall EP: Contraindications and side effects to hyperbaric oxygen treatment; in Kindwall EP, Whelan HT (eds): Hyperbaric Medicine Practice. Flagstaff, Best Publishing, 1999.
  42. Balentine JD: Selective vulnerability of the central nervous system to hyperbaric oxygen. Adv Exp Med Biol 1973;37A:293–298.
  43. Elayan IM, Axley MJ, Prasad PV, Ahlers ST, Auker CR: Effect of hyperbaric oxygen treatment on nitric oxide and oxygen free radicals in rat brain. J Neurophysiol 2000;83:2022–2029.
  44. Narkowicz CK, Vial JH, McCartney PW: Hyperbaric oxygen therapy increases free radical levels in the blood of humans. Free Radic Res Commun 1993;19:71–80.
  45. Jamieson D: Oxygen toxicity and reactive oxygen metabolites in mammals. Free Radic Biol Med 1989;7:87–108.
  46. Torbati D, Church DF, Keller JM, Pryor WA: Free radical generation in the brain precedes hyperbaric oxygen-induced convulsions. Free Radic Biol Med 1992;13:101–106.
  47. Hink J, Jansen E: Are superoxide and/or hydrogen peroxide responsible for some of the beneficial effects of hyperbaric oxygen therapy? Med Hypotheses 2001;57:764–769.
  48. Noda Y, MeGeer PL, McGeer EG: Lipid peroxide distribution in brain and the effect of hyperbaric oxygen. J Neurochem 1983;40:1329–1332.
  49. Hjelde A, Hjelstuen M, Haraldseth O, Martin JD, Thom SR, Brubakk AO: Hyperbaric oxygen and neutrophil accumulation/tissue damage during permanent focal cerebral ischaemia in rats. Eur J Appl Physiol 2002;86:401–405.
  50. Mink RB, Dutka AJ: Hyperbaric oxygen after global cerebral ischemia in rabbits does not promote brain lipid peroxidation. Crit Care Med 1995;23:1398–1404.
  51. Schäbitz WR, Schade H, Heiland S, Kollmar R, Bardutsky J, Henninger N, Müller H, Carl U, Toyokuni S, Sommer C, Schwab S: Neuroprotection by hyperbaric oxygenation after experimental focal cerebral ischemia monitored by MRI. Stroke 2004;35:1175–1179.
  52. Chavko M, Braisted JB, Outsa NJ, Harabin AL: Role of cerebral blood flow in seizures from hyperbaric oxygen exposure. Brain Res 1998;791:75–82.
  53. Demchenko IT, Boso AE, O’Neill TJ, Bennett PB, Piantadosi CA: Nitric oxide and cerebral blood flow responses to hyperbaric oxygen. J Appl Physiol 2000;88:1381–1389.
  54. Bergø GW, Tysenbotn I: Cerebral blood flow and systemic hemodynamics during exposure to 2 kPa CO2 – 300 kPa O2 in rats. J Appl Physiol 1995;78:2100–2108.
  55. Demchenko IT, Boso AE, Whorton AR, Piantadosi CA: Nitric oxide production is enhanced in rat brain before oxygen-induced convulsions. Brain Res 2001;917:253–261.
  56. Labrouche S, Javorschi S, Leroy D, Gbikpi-Benissan G, Freyburger G: Influence of hyperbaric oxygen on leukocyte functions and haemostasis in normal volunteer divers. Thromb Res 1999;96:309–315.
  57. Hampson N, Atik D: Central nervous system oxygen toxicity during routine hyperbaric oxygen toxicity. Undersea Hyperb Med 2003;30:147–153.
  58. Hampson NB, Simonson SG, Kramer CC, Piantadosi CA: Central nervous system oxygen toxicity during hyperbaric treatment of patients with carbon monoxide poisoning. Undersea Hyperb Med 1996;23:215–219.
  59. Weinstein PR, Anderson GG, Telles DA: Results of hyperbaric oxygen therapy during temporary middle cerebral artery occlusion in unanesthetized cats. Neurosurgery 1987;20:518–524.
  60. Kawamura S, Yausi N, Shirasawa M, Fukasawa H: Therapeutic effects of hyperbaric oxygenation on acute focal cerebral ischemia in rats. Surg Neurol 1990;34:101–106.
  61. Roos JA, Jackson-Friedman C, Lyden P: Effects of hyperbaric oxygen on neurologic outcome for cerebral ischemia in rats. Acad Emerg Med 1998;5:18–24.
  62. Veltkamp R, Warner DS, Domoki R, Brinkhous AD, Toole JF, Busija DW: Hyperbaric oxygen decreases infarct size and behavioral deficit after transient focal cerebral ischemia in rats. Brain Res 2000;853:68–73.
  63. Badr AE, Yin W, Mychaskiw G, Zhang JH: Effect of hyperbaric oxygen on striatal metabolites: a microdialysis study in awake freely moving rats after MCA occlusion. Brain Res 2001;916:85–90.
  64. Yin W, Badr AE, Myechaskiw G, Zhang JH: Downregulation of COX-2 is involved in hyperbaric oxygen treatment in a rat transient focal cerebral ischemia model. Brain Res 2002;926:165–171.
  65. Lou M, Eschenfelder CC, Herdegen T, Brecht S, Deuschl G: Therapeutic window for use of hyperbaric oxygenation in focal transient ischemia in rats. Stroke 2004;35:578–583.
  66. Corkill G, Van Housen K, Hein L, Reitan J: Videodensitometric estimation of the protective effect of hyperbaric oxygen in the ischemic gerbil brain. Surg Neurol 1985;24:206–210.
  67. Burt JT, Kapp JP, Smith RR: Hyperbaric oxygen and cerebral infarction in the gerbil. Surg Neurol 1987;28:265–268.
  68. Reitan JA, Kien ND, Thorup S, Corkill G: Hyperbaric oxygen increases survival following carotid ligation in gerbils. Stroke 1990;21:119–123.
  69. Krakovsky M, Rogatsky G, Zarchin N, Mayevsky A: Effect of hyperbaric oxygen therapy on survival after global cerebral ischemia in rats. Surg Neurol 1998;49:412–416.
  70. Shiokawa O, Fujishima M, Yanai T, Ibayashi S, Ueda K, Yagi H: Hyperbaric oxygen therapy in experimentally induced acute cerebral ischemia. Undersea Biomed Res 1986;13:337–344.
  71. Takahashi M, Iwatsuki N, Ono K, Tajima T, Akama M, Koga Y: Hyperbaric oxygen therapy accelerates neurologic recovery after 15-minute complete global cerebral ischemia in dogs. Crit Care Med 1992;20:1588–1594.
  72. Iwatsuki N, Takahasi M, Ono K, Tajima T: Hyperbaric oxygen combined with nicardipine administration accelerates neurologic recovery after cerebral ischemia in a canine model. Crit Care Med 1994;22:858–863.
  73. Zhou C, Li Y, Nanda A, Zhang JH: HBO suppresses Nogo-A, Ng-R, or RhoA expression in the cerebral cortex after global ischemia. Biochem Biophys Res Commun 2003;309:368–376.
  74. Neubauer RA, End E: Hyperbaric oxygenation as an adjunct therapy in strokes due to thrombosis. Stroke 1980;11:297–300.
  75. Kapp JP: Neurological response to hyperbaric oxygen – a criterion for cerebral revascularization. Surg Neurol 1981;15:43–46.
  76. Holbach KH, Wassmann H: Neurological and EEG analytical findings in the treatment of cerebral infarction with repetitive hyperbaric oxygenation. Proc 6th Int Cong Hyperbaric Med, Aberdeen,1977, pp 205–210.
  77. Hart GB, Thompson RE: Treatment of cerebral ischemia with hyperbaric oxygen. Stroke 1971;2:247–250.
  78. Anderson DC, Bottini AG, Jagiella WM, Westphal B, Ford S, Rockswold GL, Loewenson RB: A pilot study of hyperbaric oxygen in the treatment of human stroke. Stroke 1991;22:1137–1142.
  79. Nighoghossian N, Trouillas P, Adeleine P, Salford F: Hyperbaric oxygen in the treatment of acute ischemic stroke: a double-blind pilot study. Stroke 1995;26:1369–1372.
  80. Rusyniak DE, Kirk MA, May JD, Kao LW, Brizendine EJ, Welch JL, Cordell WH, Alonso RJ: Hyperbaric oxygen therapy in acute ischemic stroke results of the hyperbaric oxygen in acute ischemic stroke trial pilot study. Stroke 2003;34:571–574.

    External Resources

  81. Rogatsky GG, Shifrin EG, Mayevsky A: Optimal dosing as a necessary condition for the efficacy of hyperbaric oxygen therapy in acute ischemic stroke: a critical review. Neurol Res 2003;25:95–98.
  82. Flynn EP, Auer RN: Eubaric hyperoxemia and experimental cerebral infarction. Ann Neurol 2002;52:566–572.
  83. Singhal AB, Dijkhuizen RM, Rosen BR, Lo EH: Normobaric hyperoxia reduces MRI diffusion abnormalities and infarct size in experimental stroke. Neurology 2002;58:945–952.
  84. Singhal AB, Wang X, Sumii T, Mori T, Lo EH: Effects of normobaric hypoxia in a rat model of focal cerebral ischemia reperfusion. J Cereb Blood Flow Metab 2002;22:861–868.
  85. Gladstone DJ, Black SE, Hakim AM, et al: Toward wisdom from failure. Lessons from neuroprotective stroke trials and new therapeutic directions. Stroke 2002;33:2123–2136.
  86. Stroke Therapy Academic Industry Roundtable: Recommendations for standards regarding preclinical neuroprotective and restorative drug development. Stroke 1999;30:2752–2758.

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