Hyperbaric oxygen therapy applied research in traumatic brain injury: from mechanisms to clinical investigation

Abstract

Traumatic brain injury (TBI) is the leading cause of mortality and morbidity for millions of young people and military personnel around the world every year. Regardless of severity, neurological dysfunction is a sequela of TBI. Although many preclinical and clinical trials have been carried out to explore its underlying pathophysiology, few effective treatment options have been used to ameliorate the prognosis of TBI, particularly with regard to the recovery of neurological deficits. Translational medicine has increasingly emphasized secondary brain injury, as distinguished from the mechanical damage occurring at the moment of traumatic impact; this includes cerebral ischemia, vasospasm, metabolic dysfunction, oxygenation absence and edema. Hyperbaric oxygen therapy (HBOT) is defined as the inhalation of pure oxygen in a hyperbaric chamber that is pressurized to greater than 1 atm. High concentrations of oxygen in the blood could affect brain tissue hypoxia readily thereby avoiding neuronal cell death through increased cerebral oxygen metabolism. Therefore, HBOT has been suggested as a scientific and effective treatment for TBI. The effectiveness and feasibility of HBOT has been confirmed by several studies. Following the widespread application of HBOT in cerebrovascular diseases and TBI, non-standard therapies frequently occur in primary care institutions, causing great controversy. The systematic analysis of the progress of both animal and clinical studies in this article provides the basis for further study of HBOT.

Hyperbaric oxygen alleviates the activation of NLRP-3-inflammasomes in traumatic brain injury

“…The roles of hyperoxia during major brain injury remains controversial; however, previous studies in animal models and in humans have confirmed a theoretical basis for HBO therapy and attempted to explore its potential mechanism ( 12 , 14 ). The present study demonstrated that in a mouse model of CCI, HBO treatment ameliorated the production of IL-1β and IL-18 via inhibiting NLRP-3 inflammasome activation.…”

“…Hyperbaric oxygen (HBO) therapy, a well-established treatment in which a patient is administered at 1.5–3 absolute atmospheres (ATA) for 1–2 h, is considered safe, and can provide obvious neuroprotection both in experimental and clinical studies, especially performed within 6 h post-TBI ( 11 – 13 ). HBO can promote neuronal metabolism, inhibit brain edema, protect the integrity of the blood-brain barrier (BBB), decrease cell apoptosis and inhibit the accumulation of inflammatory cells ( 14 ). However, its underlying mechanism is poorly understood.…”

Predictive Value of CTA Spot Sign on Hematoma Expansion in Intracerebral Hemorrhage Patients

“…HBOT makes use of increased total atmospheric pressure and partial pressure of oxygen over ambient partial pressures to intervene with genes in cells, including upregulation of trophic and anti-inflammatory genes and downregulation of proinflammatory and apoptotic genes [ 60 ]. Evidence suggests HBOT could improve the effectiveness of impaired blood brain barrier and cytotoxic edema following traumatic brain injury and promote the recovery of neurons [ 61 ], which is especially fit for hemorrhage recovery. However, HBOT is simply a supplementary means and not a direct treatment of HE.…”

Hyperbaric oxygen in chronic traumatic brain injury: oxygen, pressure, and gene therapy

“…An earlier review [ 39 ] mentions only the oxygen component of HBOT. A third review [ 40 ] noted, “Unfortunately, agreement that HBOT has a positive effect on TBI has not yet been reached due to the difference in external conditions.” Absent in this review was a discussion on the different doses of HBOT used in the various studies and the erroneous assumption in two of the studies that the “sham” groups were not treatment groups that used different doses of hyperbaric therapy. This erroneous assumption is present in all of the DoD mTBI HBOT PPCS studies [ 7 , 8 ].…”