Hyperbaric Oxygen Therapy for Veterans With TBI and PCS: A Biomarker Study

This prospective, single-group study will evaluate changes in blood biomarkers following hyperbaric oxygen therapy (HBOT) in approximately 34 military veterans with a history of traumatic brain injury (TBI) and persistent post-concussive symptoms (PCS). The primary objective is to assess changes from baseline to completion of treatment in biomarkers associated with inflammation (CRP, IL-1, IL-6, IL-10, and TNF-α), neurotrophic activity (BDNF), and neuronal injury (NfL, GFAP, BD-tau, and UCH-L1). An exploratory objective is to assess whether biomarker changes differ between participants with and without comorbid post-traumatic stress disorder (PTSD). Before treatment, participants will undergo medical and behavioral health evaluations to determine their suitability for HBOT. Eligible participants will complete a baseline blood draw for biomarker analysis and standard laboratory testing. Demographic, military service, and relevant clinical information will also be collected. All participants will receive 40 HBOT sessions in a multiplace chamber at 2.0 atmospheres absolute (ATA). During each session, participants will breathe 100% oxygen for two 30-minute periods separated by a 5-minute air break. Sessions will be scheduled twice daily, Monday through Friday, with at least four hours between sessions. Blood collection and standard laboratory testing will be repeated after the 40-session protocol. The study will use a pretest-posttest design without randomization or a control group. Within-participant biomarker changes will be evaluated using paired statistical tests, with adjustments for multiple comparisons in the primary biomarker analyses. Comparisons by comorbid PTSD status and associations between biomarker changes and clinical outcomes will be exploratory. Because all participants receive HBOT, observed changes cannot be attributed to HBOT alone.