Hyperbaric oxygen (HBO2) has been shown to improve outcome after severe traumatic brain injury, but its underlying mechanisms are unknown. Following lateral fluid-percussion injury (FPI), the authors tested the effects of HBO2 treatment as well as enhanced normobaric oxygenation on mitochondrial function, as measured by both cognitive recovery and cellular adenosine triphosphate (ATP) levels.
Adult male Sprague–Dawley rats were subjected to moderate lateral FPI or sham injury and were allocated to one of four treatment groups: 1) FPI treated with 4 hours of normobaric 30% O2; 2) FPI treated with 4 hours of normobaric 100% O2; 3) FPI treated with 1 hour of HBO2 plus 3 hours of normobaric 100% O2; and 4) sham-injured treated with normobaric 30% O2. Cognitive outcome was assessed using the Morris water maze (MWM) on Days 11 to 15 after injury. Animals were then killed 21 days postinjury to assess hippocampal neuronal loss. Adenosine triphosphate was extracted from the neocortex and measured using high-performance liquid chromatography. The results showed that injured animals treated with HBO2 or normobaric 100% O2 alone had significantly higher levels of cerebral ATP as compared with animals treated using normobaric 30% O2 (p ≤ 0.05). The injured animals treated with HBO2 had significant improvements in cognitive recovery, as characterized by a shorter latency in MWM performance (p ≤ 0.05), and decreased neuronal loss in the CA2/3 and hilar regions as compared with those treated with 30% or 100% O2 (p ≤ 0.05).
Both hyperbaric and normobaric hyperoxia increased cerebral ATP levels after lateral FPI. In addition, HBO2 treatment improved cognitive recovery and reduced hippocampal neuronal cell loss after brain injury in the rat.
Abbreviations used in this paper:ADP = adenosine diphosphate; AMP = adenosine monophosphate; ANOVA = analysis of variance; ata = atm absolute; ATP = adenosine triphosphate; DHR = dihydrorhodamine 123; FPI = fluid-percussion injury; HBO2 = hyperbaric oxygen; HPLC = high-performance liquid chromatography; ICP = intracranial pressure; MWM = Morris water maze; NAD = nicotinamide adenine dinucleotide; NADH = reduced form of nicotinamide adenine dinucleotide; ROS = reactive oxygen species; SEM = standard error of the mean; TBI = traumatic brain injury.
Address reprint requests to: M. Ross Bullock, M.D., Ph.D., Department of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, 1200 East Broad Street, West Hospital 8 South, Richmond, Virginia 23298-0631. email:
Mbullock@mcvh-vcu.edu.Current address for Dr. Daugherty: Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota.
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