Hyperbaric oxygen therapy for traumatic brain injury

Hyperbaric oxygen therapy (HBOT) is a treatment by which 100% oxygen is administered to a patient at a pressure greater than atmospheric pressure at sea level (i.e. one atmosphere absolute, ATA) [1]. The increased partial pressure of oxygen (pO2) within the blood and subsequent improved mitochondrial metabolism/tissue oxygenation constitutes the net effect of HBOT [2-6]. Given that the dissolved oxygen content in the plasma increases linearly after hemoglobin is 100% saturated [7,8], plasma bound oxygen can be used more readily than that bound to hemoglobin which enables tissue oxygen delivery even in the absence of red blood cells [7,9].Thus, HBOT induces a much larger oxygen-carrying capacity in the blood that dramatically increases the driving force of oxygen diffusion to tissues. Although HBOT-induced cerebral vasoconstriction appears to be undesirable within the context of ischemic conditions [10,11] this may not be necessarily deleterious due to increased oxygen availability to injured tissues. HBOT may also counter vasodilation of the capillaries within hypoxic tissues, thereby minimizing collection of extravascular fluids (edema) which ultimately reduces brain vasogenic edema and the ensuing decrease in intracranial pressure (ICP) [5,12-14].Emerging evidence has shown the neuroprotective effects of HBOT in a range of multiple injuries and/or disorders (Additional file 1, Table S1) [15]. The most common clinical applications include decompression sickness, carbon monoxide poisoning, minimization of radiation therapy induced tissue damage and enhancing skin grafts [1,16], which are all covered by insurance/Medicare. There are numerous "unapproved" uses of HBOT that focus on more complex neurological disorders, including autism, multiple sclerosis and stroke, which have shown promising results in experimental settings, but clinical efficacy is still elusive. Recent efforts have applied HBOT to traumatic brain injury [5,14,17]. While significant research on HBOT