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Hyperbaric oxygen therapy as a potential treatment for post-traumatic stress disorder associated with traumatic brain injury

Authors Eve DJ, Steele MR, Sanberg PR, Borlongan CV

Received 8 April 2016

Accepted for publication 12 July 2016

Published 20 October 2016 Volume 2016:12 Pages 2689—2705


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Dr Roger Pinder

David J Eve,1 Martin R Steele,2 Paul R Sanberg,1 Cesar V Borlongan1

1Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and Brain Repair, Morsani College of Medicine, 2Veterans Reintegration Steering Committee, Veterans Research, University of South Florida, Tampa, FL, USA

Abstract: Traumatic brain injury (TBI) describes the presence of physical damage to the brain as a consequence of an insult and frequently possesses psychological and neurological symptoms depending on the severity of the injury. The recent increased military presence of US troops in Iraq and Afghanistan has coincided with greater use of improvised exploding devices, resulting in many returning soldiers suffering from some degree of TBI. A biphasic response is observed which is first directly injury-related, and second due to hypoxia, increased oxidative stress, and inflammation. A proportion of the returning soldiers also suffer from post-traumatic stress disorder (PTSD), and in some cases, this may be a consequence of TBI. Effective treatments are still being identified, and a possible therapeutic candidate is hyperbaric oxygen therapy (HBOT). Some clinical trials have been performed which suggest benefits with regard to survival and disease severity of TBI and/or PTSD, while several other studies do not see any improvement compared to a possibly poorly controlled sham. HBOT has been shown to reduce apoptosis, upregulate growth factors, promote antioxidant levels, and inhibit inflammatory cytokines in animal models, and hence, it is likely that HBOT could be advantageous in treating at least the secondary phase of TBI and PTSD. There is some evidence of a putative prophylactic or preconditioning benefit of HBOT exposure in animal models of brain injury, and the optimal time frame for treatment is yet to be determined. HBOT has potential side effects such as acute cerebral toxicity and more reactive oxygen species with long-term use, and therefore, optimizing exposure duration to maximize the reward and decrease the detrimental effects of HBOT is necessary. This review provides a summary of the current understanding of HBOT as well as suggests future directions including prophylactic use and chronic treatment.

Keywords: mild moderate and severe TBI, clinical trials, reactive oxygen species, acoustic startle response, elevated plus maze, cutoff behavioral criteria, prophylactic use, preconditioning, inflammation, acute and chronic treatment

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