Neurochemical Research

, Volume 39, Issue 5, pp 950–960 | Cite as

Hyperbaric Oxygen Therapy Ameliorates Local Brain Metabolism, Brain Edema and Inflammatory Response in a Blast-Induced Traumatic Brain Injury Model in Rabbits

  • Yongming Zhang
  • Yanyan Yang
  • Hong Tang
  • Wenjiang Sun
  • Xiaoxing Xiong
  • Daniel Smerin
  • Jiachuan Liu
Original Paper


Many studies suggest that hyperbaric oxygen therapy (HBOT) can provide some clinically curative effects on blast-induced traumatic brain injury (bTBI). The specific mechanism by which this occurs still remains unknown, and no standardized time or course of hyperbaric oxygen treatment is currently used. In this study, bTBI was produced by paper detonators equivalent to 600 mg of TNT exploding at 6.5 cm vertical to the rabbit’s head. HBO (100 % O2 at 2.0 absolute atmospheres) was used once, 12 h after injury. Magnetic resonance spectroscopy was performed to investigate the impact of HBOT on the metabolism of local injured nerves in brain tissue. We also examined blood–brain barrier (BBB) integrity, brain water content, apoptotic factors, and some inflammatory mediators. Our results demonstrate that hyperbaric oxygen could confer neuroprotection and improve prognosis after explosive injury by promoting the metabolism of local neurons, inhibiting brain edema, protecting BBB integrity, decreasing cell apoptosis, and inhibiting the inflammatory response. Furthermore, timely intervention within 1 week after injury might be more conducive to improving the prognosis of patients with bTBI.


Brain injury Explosive injury Rabbit Magnetic resonance spectrum Hyperbaric oxygen 



This study was supported by research Grants from the Nature Science Youth Funding of Anhui Province (1208085QH171) and Nanjing Military Region Fund Project (10MB009). We also thank Professor Bingchang Li (Institute of Battle Surgical Research, Third Military Medicine University) for his support while creating our animal model and Daniel Smerin for his manuscript editing.

Conflict of interest

We have no conflicts of interest to declare.


  1. 1.
    Huang E, Ngo M, Yee S, Held L, Norman K, Scremin AM, Scremin O (2013) Repeated blast exposure alters open field behavior recorded under low illumination. Brain Res 1529:125–133PubMedCrossRefGoogle Scholar
  2. 2.
    Ling G, Bandak F, Armonda R, Grant G, Ecklund J (2009) Explosive blast neurotrauma. J Neurotrauma 26:815–825PubMedCrossRefGoogle Scholar
  3. 3.
    Davenport ND, Lim KO, Armstrong MT, Sponheim SR (2012) Diffuse and spatially variable white matter disruptions are associated with blast-related mild traumatic brain injury. Neuroimage 59:2017–2024PubMedCrossRefGoogle Scholar
  4. 4.
    Armonda RA, Bell RS, Vo AH, Ling G, DeGraba TJ, Crandall B, Ecklund J, Campbell WW (2006) Wartime traumatic cerebral vasospasm: recent review of combat casualties. Neurosurgery 59:1215–1225; (discussion 1225)Google Scholar
  5. 5.
    Tang X, Liu KJ, Ramu J, Chen Q, Li T, Liu W (2010) Inhibition of gp91(phox) contributes towards normobaric hyperoxia afforded neuroprotection in focal cerebral ischemia. Brain Res 1348:174–180PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Edwards ML (2010) Hyperbaric oxygen therapy. Part 1: history and principles. J Vet Emerg Crit Care 20:284–288CrossRefGoogle Scholar
  7. 7.
    Voigt C, Forschler A, Jaeger M, Meixensberger J, Kuppers-Tiedt L, Schuhmann MU (2008) Protective effect of hyperbaric oxygen therapy on experimental brain contusions. Acta Neurochir Suppl 102:441–445PubMedCrossRefGoogle Scholar
  8. 8.
    Palzur E, Zaaroor M, Vlodavsky E, Milman F, Soustiel JF (2008) Neuroprotective effect of hyperbaric oxygen therapy in brain injury is mediated by preservation of mitochondrial membrane properties. Brain Res 1221:126–133PubMedCrossRefGoogle Scholar
  9. 9.
    Rockswold SB, Rockswold GL, Defillo A (2007) Hyperbaric oxygen in traumatic brain injury. Neurol Res 29:162–172PubMedCrossRefGoogle Scholar
  10. 10.
    Qian J, Qian B, Lei H (2013) Reversible loss of N-acetylaspartate after 15-min transient middle cerebral artery occlusion in rat: a longitudinal study with in vivo proton magnetic resonance spectroscopy. Neurochem Res 38:208–217PubMedCrossRefGoogle Scholar
  11. 11.
    Sidaros A, Herning M (2007) Magnetic resonance imaging in severe traumatic brain injury. Ugeskr Laeg 169:214–216PubMedGoogle Scholar
  12. 12.
    Kamnaksh A, Kovesdi E, Kwon SK, Wingo D, Ahmed F, Grunberg NE, Long J, Agoston DV (2011) Factors affecting blast traumatic brain injury. J Neurotrauma 28:2145–2153PubMedCrossRefGoogle Scholar
  13. 13.
    Yong-Ming Z, Jia-Chuan L, Yan-Yan Y, Wen-Jiang S, Hong T, Bing-Cang L, Liang-Chao Z (2012) Effective protection of rabbits’ explosive brain injury through blocking gap junction communication. Afr Health Sci 12:552–556PubMedCentralPubMedGoogle Scholar
  14. 14.
    Soares DP, Law M (2009) Magnetic resonance spectroscopy of the brain: review of metabolites and clinical applications. Clin Radiol 64:12–21PubMedCrossRefGoogle Scholar
  15. 15.
    Li CX, Wang Y, Gao H, Pan WJ, Xiang Y, Huang M, Lei H (2008) Cerebral metabolic changes in a depression-like rat model of chronic forced swimming studied by ex vivo high resolution 1H magnetic resonance spectroscopy. Neurochem Res 33:2342–2349PubMedCrossRefGoogle Scholar
  16. 16.
    Brugger S, Davis JM, Leucht S, Stone JM (2011) Proton magnetic resonance spectroscopy and illness stage in schizophrenia—a systematic review and meta-analysis. Biol Psychiatry 69:495–503PubMedCrossRefGoogle Scholar
  17. 17.
    Ren C, Gao X, Niu G, Yan Z, Chen X, Zhao H (2008) Delayed postconditioning protects against focal ischemic brain injury in rats. PLoS One 3:e3851PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Yang DY, Pan HC, Chen CJ, Cheng FC, Wang YC (2007) Effects of tissue plasminogen activator on cerebral microvessels of rats during focal cerebral ischemia and reperfusion. Neurol Res 29:274–282PubMedCrossRefGoogle Scholar
  19. 19.
    Magnuson J, Leonessa F, Ling GS (2012) Neuropathology of explosive blast traumatic brain injury. Curr Neurol Neurosci Rep 12:570–579PubMedCrossRefGoogle Scholar
  20. 20.
    Dewall J (2010) The ABCs of TBI. Evidence-based guidelines for adult traumatic brain injury care. J Emerg Med Serv 35:54-61; quiz 63Google Scholar
  21. 21.
    Ling GS, Ecklund JM (2011) Traumatic brain injury in modern war. Curr Opin Anaesthesiol 24:124–130PubMedCrossRefGoogle Scholar
  22. 22.
    Liu Z, Jiao QF, You C, Che YJ, Su FZ (2006) Effect of hyperbaric oxygen on cytochrome C, Bcl-2 and Bax expression after experimental traumatic brain injury in rats. Chin J Traumatol 9:168–174PubMedGoogle Scholar
  23. 23.
    Niklas A, Brock D, Schober R, Schulz A, Schneider D (2004) Continuous measurements of cerebral tissue oxygen pressure during hyperbaric oxygenation–HBO effects on brain edema and necrosis after severe brain trauma in rabbits. J Neurol Sci 219:77–82PubMedCrossRefGoogle Scholar
  24. 24.
    Wright JK, Zant E, Groom K, Schlegel RE, Gilliland K (2009) Case report: treatment of mild traumatic brain injury with hyperbaric oxygen. Undersea Hyperb Med 36:391–399PubMedGoogle Scholar
  25. 25.
    Rockswold SB, Rockswold GL, Zaun DA, Zhang X, Cerra CE, Bergman TA, Liu J (2010) A prospective, randomized clinical trial to compare the effect of hyperbaric to normobaric hyperoxia on cerebral metabolism, intracranial pressure, and oxygen toxicity in severe traumatic brain injury. J Neurosurg 112:1080–1094PubMedCrossRefGoogle Scholar
  26. 26.
    Edwards ML (2010) Hyperbaric oxygen therapy. Part 2: application in disease. J Vet Emerg Crit Care 20:289–297CrossRefGoogle Scholar
  27. 27.
    Harch PG, Kriedt C, Van Meter KW, Sutherland RJ (2007) Hyperbaric oxygen therapy improves spatial learning and memory in a rat model of chronic traumatic brain injury. Brain Res 1174:120–129PubMedCrossRefGoogle Scholar
  28. 28.
    Wang GH, Zhang XG, Jiang ZL, Li X, Peng LL, Li YC, Wang Y (2010) Neuroprotective effects of hyperbaric oxygen treatment on traumatic brain injury in the rat. J Neurotrauma 27:1733–1743PubMedCrossRefGoogle Scholar
  29. 29.
    Marx RE, Ehler WJ, Tayapongsak P, Pierce LW (1990) Relationship of oxygen dose to angiogenesis induction in irradiated tissue. Am J Surg 160:519–524PubMedCrossRefGoogle Scholar
  30. 30.
    Ballabh P, Braun A, Nedergaard M (2004) The blood–brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis 16:1–13PubMedCrossRefGoogle Scholar
  31. 31.
    Lee JH, Cui HS, Shin SK, Kim JM, Kim SY, Lee JE, Koo BN (2013) Effect of propofol post-treatment on blood–brain barrier integrity and cerebral edema after transient cerebral ischemia in rats. Neurochem Res 38:2276–2286PubMedCrossRefGoogle Scholar
  32. 32.
    Rosenthal RE, Silbergleit R, Hof PR, Haywood Y, Fiskum G (2003) Hyperbaric oxygen reduces neuronal death and improves neurological outcome after canine cardiac arrest. Stroke 34:1311–1316PubMedCrossRefGoogle Scholar
  33. 33.
    Hollin SA, Sukoff MH, Jacobson JH 2nd (1968) The protective effect of hyperbaric oxygenation in experimentally produced cerebral edema and compression. Prog Brain Res 30:479–489PubMedCrossRefGoogle Scholar
  34. 34.
    Gill AL, Bell CN (2004) Hyperbaric oxygen: its uses, mechanisms of action and outcomes. QJM 97:385–395PubMedCrossRefGoogle Scholar
  35. 35.
    Marino S, Zei E, Battaglini M, Vittori C, Buscalferri A, Bramanti P, Federico A, De Stefano N (2007) Acute metabolic brain changes following traumatic brain injury and their relevance to clinical severity and outcome. J Neurol Neurosurg Psychiatry 78:501–507PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    McLean MA, Cross JJ (2009) Magnetic resonance spectroscopy: principles and applications in neurosurgery. Br J Neurosurg 23:5–13PubMedCrossRefGoogle Scholar
  37. 37.
    Lin JW, Tsai JT, Lee LM, Lin CM, Hung CC, Hung KS, Chen WY, Wei L, Ko CP, Su YK, Chiu WT (2008) Effect of hyperbaric oxygen on patients with traumatic brain injury. Acta Neurochir Suppl 101:145–149PubMedCrossRefGoogle Scholar
  38. 38.
    Wennersten A, Holmin S, Mathiesen T (2003) Characterization of Bax and Bcl-2 in apoptosis after experimental traumatic brain injury in the rat. Acta Neuropathol 105:281–288PubMedGoogle Scholar
  39. 39.
    Kang GH, Yan BC, Cho GS, Kim WK, Lee CH, Cho JH, Kim M, Kang IJ, Won MH, Lee JC (2012) Neuroprotective effect of fucoidin on lipopolysaccharide accelerated cerebral ischemic injury through inhibition of cytokine expression and neutrophil infiltration. J Neurol Sci 318:25–30PubMedCrossRefGoogle Scholar
  40. 40.
    Chamorro A, Hallenbeck J (2006) The harms and benefits of inflammatory and immune responses in vascular disease. Stroke 37:291–293PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Samson Y, Lapergue B, Hosseini H (2005) Inflammation and ischaemic stroke: current status and future perspectives. Revue Neurol 161:1177–1182CrossRefGoogle Scholar
  42. 42.
    Hedges JC, Singer CA, Gerthoffer WT (2000) Mitogen-activated protein kinases regulate cytokine gene expression in human airway myocytes. Am J Respir Cell Mol Biol 23:86–94PubMedCrossRefGoogle Scholar
  43. 43.
    Emerich DF, Dean RL 3rd, Bartus RT (2002) The role of leukocytes following cerebral ischemia: pathogenic variable or bystander reaction to emerging infarct? Exp Neurol 173:168–181PubMedCrossRefGoogle Scholar
  44. 44.
    Witko-Sarsat V, Rieu P, Descamps-Latscha B, Lesavre P, Halbwachs-Mecarelli L (2000) Neutrophils: molecules, functions and pathophysiological aspects. Lab Invest 80:617–653PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Yongming Zhang
    • 1
    • 2
  • Yanyan Yang
    • 1
  • Hong Tang
    • 1
  • Wenjiang Sun
    • 1
  • Xiaoxing Xiong
    • 2
  • Daniel Smerin
    • 3
  • Jiachuan Liu
    • 1
  1. 1.Department of Neurosurgery, No. 105 Hospital of PLAAnhui Medicine UniversityHefeiPeople’s Republic of China
  2. 2.Department of NeurosurgeryStanford UniversityStanfordUSA
  3. 3.School of MedicineStanford UniversityStanfordUSA

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