4 million people yearly [41]. Although the primary injury to Etoposide mw the brain sustained at the time of the trauma is usually not reversible, it is the secondary injury occurring in the hours and days following the initial injury that provides more opportunities for treatment to preserve tissue and function. In addition to the initial injury, a large contributor to morbidity and mortality is cerebral ischemia resulting from post-traumatic hypoxia and hypotension [42]. On a microscopic level, abnormalities

of calcium and potassium homeostasis, mechanical membrane disruption, excitotoxicity, and altered glucose metabolism also contribute to cellular damage, which in turn cause edema and neuronal cell death [43]. Cell death in the form of both necrosis and apoptosis occurs in the areas surrounding the primary injury, but can also occur at more distant areas [44]. Increased intracranial pressure from edema, as well as from contusions and hemorrhages, contributes to secondary injury by increasing ischemia, and derangement of cellular metabolism, and can lead to herniation and death [45] and [46]. The interest in using HBO2T

to treat TBI is based upon the premise that hypoxia, edema and apoptosis learn more play significant roles in the pathophysiology of the disease. Only a few studies have directly compared HBO2T to standard of care in acute TBI. Most recently Rockswold et al. [47] published a treatment effect in acute TBI lowering intracranial pressure for 3 days using 60 min of HBO2T at 1.5 ATA. In 1976, Artru et al. [48] randomized 60 patients

who were in coma after TBI for an average of 4.5 days after their injuries, and treated them at 2.5 ATA for 60 min daily over 10 days with a 4 day break repeated versus standard of care. At one year, the study showed non-significant trends towards shorter coma and higher rate of consciousness in the HBO2T group. Mortality was not affected. The only significant improvements were in a subgroup of young patients with brainstem injury who had higher rates of consciousness at one month, (HBO2T 67% vs control 11%). In 1974, Holbach alternated 99 patients ID-8 in coma with acute midbrain syndrome to either standard care or HBO2T at 1.5 ATA and saw significant improvements in mortality (53% vs 74%) and good outcome on the Glasgow Outcome Scale (33% vs 6%) [49]. More recently, Rockswold et al. randomized 168 TBI patients between 6 and 24 h after injury with GCS of 9 or less to HBO2T at 1.5 ATA for 60 min every 8 h for 2 weeks versus standard care [50]. At 12 months, blinded examiners saw no change in outcome among survivors, but there was a significant decrease in mortality (17% vs 32%) at one year. A small more recent trial randomized patients at day 3 with a GCS of less than 9 to HBO2T at 2.5 ATA for 400–600 min every four days for 3 or 4 treatments versus standard care [51].