Hyperbaric Oxygen Therapy in the Treatment of Acute Severe Traumatic Brain Injury: A Systematic Review

Abstract

There has been no major advancement in a quarter of a century for the treatment of acute severe traumatic brain injury (TBI). This review summarizes 40 years of clinical and pre-clinical research on the treatment of acute TBI with hyperbaric oxygen therapy (HBO) in the context of an impending National Institute of Neurologic Disorders and Stroke-funded, multi-center, randomized, adaptive Phase II clinical trial -the Hyperbaric Oxygen Brain Injury Treatment (HOBIT) trial. Thirty studies (eight clinical and 22 pre-clinical) that administered HBO within 30 days of a TBI were identified from PubMed searches. The pre-clinical studies consistently reported positive treatment effects across a variety of outcome measures with almost no safety concerns, thus providing strong proof-of-concept evidence for treating severe TBI in the acute setting. Of the eight clinical studies reviewed, four were based on the senior author's (GR) investigation of HBO as a treatment for acute severe TBI. These studies provided evidence that HBO significantly improves physiologic measures without causing cerebral or pulmonary toxicity and can potentially improve clinical outcome. These results were consistent across the other four reviewed clinical studies, thus providing preliminary clinical data supporting the HOBIT trial. This comprehensive review demonstrates that HBO has the potential to be the first significant treatment in the acute phase of severe TBI.

Impact of Hyperbaric Oxygen Therapy on Cognitive Functions: a Systematic Review

“…Enhanced oxygen supply and increased pressure result in a wide variety of pathophysiological mechanisms. Thus, HBOT is believed to diminish neuroinflammatory responses, blood-brain barrier permeability and apoptosis while positively impacting neurogenesis, neuronal and axonal integrity and synaptogenesis (reviewed by Daly et al, 2018;Fischer et al, 2010). All of these effects may potentially influence patients' cognitive functioning.…”

<p>Hyperbaric oxygen therapy attenuates neuronal apoptosis induced by traumatic brain injury via Akt/GSK3&beta;/&beta;-catenin pathway</p>

“…However, the efficiency of HBO therapy remains extremely controversial 5–7. Several studies have reported that HBO therapy improved the neurological deficits and cognitive impairments of patients in the acute phase of severe TBI 8,9. In contrast, other studies have demonstrated that HBO therapy had no effect on patients with mild and chronic TBI 10.…”

The neuroprotection of hyperbaric oxygen therapy against traumatic brain injury via NF-κB/MAPKs-CXCL1 signaling pathway

“…In 2018, a neurosurgery clinical team from the University of Minnesota published a review on the treatment of acute TBI with HBO that collected and analyzed 30 clinical and animal research articles. Their results showed clear e cacy of HBO in the treatment of acute TBI [14]. Preliminary studies of our group also con rmed that HBO treatment can reduce secondary injury after TBI, and its mechanism of action may be related to the reduction of cerebral edema, inhibition of astrocyte proliferation, improvement of brain metabolism, and inhibition of neuroin ammation [15][16][17].…”