Neuroprotective effect of hyperbaric oxygen therapy in a juvenile rat model of repetitive mild traumatic brain injury.

Repetitive mild traumatic brain injury (rmTBI) is an important medical concern for adolescent athletes that can lead to long-term disabilities. Multiple mild injuries may exacerbate tissue damage resulting in cumulative brain injury and poor functional recovery. In the present study, we investigated the increased brain vulnerability to rmTBI and the effect of hyperbaric oxygen treatment using a juvenile rat model of rmTBI. Two episodes of mild cortical controlled impact (3 days apart) were induced in juvenile rats. Hyperbaric oxygen (HBO) was applied 1 hour/day × 3 days at 2 atmosphere absolute consecutively, starting at 1 day after initial mild traumatic brain injury (mTBI). Neuropathology was assessed by multi-modal magnetic resonance imaging (MRI) and tissue immunohistochemistry. After repetitive mTBI, there were increases in T2-weighted imaging-defined cortical lesions and susceptibility weighted imaging-defined cortical microhemorrhages, correlated with brain tissue gliosis at the site of impact. HBO treatment significantly decreased the MRI-identified abnormalities and tissue histopathology. Our findings suggest that HBO treatment improves the cumulative tissue damage in juvenile brain following rmTBI. Such therapy regimens could be considered in adolescent athletes at the risk of repeated concussions exposures.

Hyperbaric oxygen therapy for traumatic brain injury: bench-to-bedside.

Traumatic brain injury (TBI) is a serious public health problem in the United States. Survivors of TBI are often left with significant cognitive, behavioral, and communicative disabilities. So far there is no effective treatment/intervention in the daily clinical practice for TBI patients. The protective effects of hyperbaric oxygen therapy (HBOT) have been proved in stroke; however, its efficiency in TBI remains controversial. In this review, we will summarize the results of HBOT in experimental and clinical TBI, elaborate the mechanisms, and bring out our current understanding and opinions for future studies.

Is Hyperbaric Oxygen Therapy Effective for Traumatic Brain Injury? A Rapid Evidence Assessment of the Literature and Recommendations for the Field.

This systematic review examines the efficacy of hyperbaric oxygen (HBO2) for traumatic brain injury (TBI) to make evidence-based recommendations for its application and future research. A comprehensive search was conducted to identify studies through 2014. Methodological quality was assessed and synthesis and interpretation of relevant data was performed. Twelve randomized trials were included. All mild TBI studies demonstrated minimal bias and no statistically significant differences between HBO2 and sham arms. Statistically significant improvement occurred over time within both groups. Moderate-to-severe TBI studies were of mixed quality, with majority of results favoring HBO2 compared with "standard care." The placebo analysis conducted was limited by lack of details. For mild TBI, results indicate HBO2 is no better than sham treatment. Improvements within both HBO2 and sham groups cannot be ignored. For acute treatment of moderate-to-severe TBI, although methodology appears flawed across some studies, because of the complexity of brain injury, HBO2 may be beneficial as a relatively safe adjunctive therapy if feasible. Further research should be considered to resolve the controversy surrounding this field, but only if methodological flaws are avoided and bias minimized.

Treatment of persistent post-concussion syndrome due to mild traumatic brain injury: current status and future directions.

Persistent post-concussion syndrome caused by mild traumatic brain injury has become a major cause of morbidity and poor quality of life. Unlike the acute care of concussion, there is no consensus for treatment of chronic symptoms. Moreover, most of the pharmacologic and non-pharmacologic treatments have failed to demonstrate significant efficacy on both the clinical symptoms as well as the pathophysiologic cascade responsible for the permanent brain injury. This article reviews the pathophysiology of PCS, the diagnostic tools and criteria, the current available treatments including pharmacotherapy and different cognitive rehabilitation programs, and promising new treatment directions. A most promising new direction is the use of hyperbaric oxygen therapy, which targets the basic pathological processes responsible for post-concussion symptoms; it is discussed here in depth.

Simple and Procedural Reaction Time for Mild Traumatic Brain Injury in a Hyperbaric Oxygen Clinical Trial.

Simple reaction time (SRT) and procedural reaction time (PRT) are speed-of-processing tasks in the Automated Neuropsychological Assessment Metrics (ANAM) that may be sensitive to mild traumatic brain injury (mTBI). The investigators measured SRT and PRT throughput (correct responses per minute) at baseline, 6 weeks, and 13 weeks in military personnel with mTBI randomized to local care or 40 chamber sessions (sham-1.2 atmospheres absolute [ATA] air, hyperbaric oxygen-1.5 ATA O2). Scores were assessed at baseline using univariate analysis of variance and across time with repeated measures methods. Data reported as throughput standard scores (mean = 100, SD = 15). Seventy-two participants with ongoing symptoms after mTBI enrolled in the study (three female, median age 31 years, mean three lifetime concussion events, most recent mTBI 23 months prior). Sixty-four had Automated Neuropsychological Assessment Metrics data at 13 weeks. SRT and PRT throughput standard scores were comparable across groups at baseline. Over time, SRT scores did not change in the hyperbaric oxygen or sham groups and decreased in the local care group. PRT throughput standard scores increased from baseline to mid-intervention and decreased from mid-intervention to postintervention in all groups. Repeated measures change over time in SRT (p = 0.23), and PRT (p = 0.17) scores were not different among groups. This study may be underpowered to detect statistically significant change.

Hyperbaric oxygen: B-level evidence in mild traumatic brain injury clinical trials.

First, to demonstrate that B-level evidence exists for the use of hyperbaric oxygen therapy (HBOT) as an effective treatment in mild to moderate traumatic brain injury/persistent postconcussion syndrome (mTBI/PPCS). Second, to alert readers and researchers that currently used pressurized air controls (≥21% O2, >1.0 ATA) are therapeutically active and cannot be utilized as sham controls without further validation. Review of published, peer-reviewed articles of HBOT prospective and controlled clinical trials of mTBI/PPCS symptoms. Published results demonstrate that HBOT is effective in the treatment of mTBI/PPCS symptoms. Doses of oxygen that are applied at ≥21% O2 and at pressures of >1.0 ATA produce improvements from baseline measures. Some of the recently published clinical trials are mischaracterized as sham-controlled clinical trials (i.e., sham = 21% O2/1.2-1.3 ATA), but are best characterized as dose-varying (variation in oxygen concentration, pressure applied, or both) clinical trials. Hyperbaric oxygen and hyperbaric air have demonstrated therapeutic effects on mTBI/PPCS symptoms and can alleviate posttraumatic stress disorder symptoms secondary to a brain injury in 5 out of 5 peer-reviewed clinical trials. The current use of pressurized air (1.2-1.3 ATA) as a placebo or sham in clinical trials biases the results due to biological activity that favors healing.

Clinical results in brain injury trials using HBO2 therapy: Another perspective.

The current debate surrounding the use of hyperbaric oxygen (HBO2) for neurological indications, specifically mild to moderate chronic traumatic brain injury (mTBI) and post-concussion syndrome (PCS), is mired in confusion due to the use of non-validated controls and an unfamiliarity by many practitioners of HBO2 therapy with the experimental literature. In the past 40 years, the use of an air sham (21% oxygen, 1.14-1.5 atmospheres absolute/atm abs) in clinical and animal studies, instead of observational or crossover controls, has led to false acceptance of the null hypothesis (declaring no effect when one is present), due to the biological activity of these “sham” controls. The recent Department of Defense/Veterans Administration (DoD/VA) sponsored trials, previous published reports on the use of HBO2 therapy on stroke and mTBI and preliminary reports from the HOPPS Army trial, have helped to highlight the biological activity of pressurized air, validate the development of a convincing control for future studies and demonstrate the effectiveness of a hyperbaric intervention for mTBI/ PCS. Approval of HBO2 for neurological indications, especially for mTBI/PCS, should be granted at the federal, state and certifying body levels as a safe and viable treatment for recovery in the post-acute phase.