Protection of mitochondrial function and improvement in cognitive recovery in rats treated with hyperbaric oxygen following lateral fluid-percussion injury.
OBJECTIVE
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.


METHODS
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 < or = 0.05). The injured animals treated with HBO2 had significant improvements in cognitive recovery, as characterized by a shorter latency in MWM performance (p < or = 0.05), and decreased neuronal loss in the CA2/3 and hilar regions as compared with those treated with 30% or 100% O2, (p < or = 0.05).


CONCLUSIONS
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.
Zhou
Zhengwen
Z
Department of Neurosurgery, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298-0631, USA.
Daugherty
Wilson P
WP
Sun
Dong
D
Levasseur
Joseph E
JE
Altememi
Nabil
N
Hamm
Robert J
RJ
Rockswold
Gaylan L
GL
Bullock
M Ross
MR
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001930:Brain Injuries / Q000378:metabolism / Q000523:psychology / Q000628:therapy*; D002851:Chromatography, High Pressure Liquid; D003071:Cognition / Q000502:physiology*; D005609:Free Radicals / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology; D006931:Hyperbaric Oxygenation; D008297:Male; D018782:Maze Learning; D008928:Mitochondria / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology
D005609:Free Radicals; D000255:Adenosine Triphosphate