Stable Intravenous Fluorohydrocarbon Emulsion with High Oxygen Capacitance Combined with Hyperbaric Oxygen for the Acute Salvage of Tissue Injury After TBI

Abstract : The presence of hypoxia after traumatic brain injury (TBI) portends a worse outcome for recovery. Thus an important treatment target is the restoration of the disrupted oxygen delivery and utilization. Perfluorooctyl bromide (PFOB) has an unsurpassed ability to carry oxygen. Hyperbaric oxygen (HBO) has the ability to drive higher amounts of oxygen into fluids. These modalities combined together have the theoretical ability to maintain adequate oxygen delivery to the brain after traumatic brain injury (TBI). In C57 mice after mild and medium level of controlled cortical impact (CCI), we treated mice with vehicle only, hyperbaric oxygen only, PFOB only, and PFOB combined with HBOT, and then examined contusion volume (tissue loss), motor function and memory. Real-time measurements of local tissue oxygen partial pressure (PO2) in mice brain cortex demonstrated that PO2 of the injury core dropped to near zero after CCI. Significant reduction of PO2 was also observed in penumbra in the first hour after CCI. For functional test, Rotarod test, wire-grip, or Morris Water Maze, PFOB or HBO did not improve function. Brain tissue loss in oxygen treatment groups showed modest reduction but no significant improvement. Our study suggests that PFOB and/or HBOT at these doses and timing of delivery are harmful at high doses and not beneficial at lower doses.