Perfluorocarbon emulsion improves cerebral oxygenation and mitochondrial function after fluid percussion brain injury in rats.
OBJECTIVE
Cerebral ischemia is a common secondary sequela of traumatic brain injury (TBI). Experimental models of stroke have demonstrated reductions in ischemia after perfluorocarbon (PFC) administration; however, there are no published reports of PFC efficacy after TBI. The current study analyzed the effect of the PFC emulsion Oxygent (AF0144; Alliance Pharmaceutical Corp., San Diego, CA) on cerebral oxygenation, mitochondrial redox potential, and free radical formation after lateral fluid percussion injury.


METHODS
After fluid percussion injury, five 2.25 ml/kg doses of PFC or saline were administered to rats breathing 100% O(2), and oxygen tension was recorded. In a second experiment, a single bolus (11.25 ml/kg) of PFC or saline was given after injury, and redox potential and free radical formation were measured at 1 or 4 hours with Alamar blue dye and dihydrorhodamine 123, respectively.


RESULTS
Cerebral oxygen tension was significantly increased in both injured and sham animals treated with 11.25 ml/kg of PFC as compared with saline (P < 0.05). Likewise, PFC significantly increased mitochondrial redox potential as compared with saline at 4 hours after injury (P < 0.01). Mitochondrial peroxynitrite and peroxide production also increased with the administration of PFC (P < 0.05).


CONCLUSIONS
The current study demonstrates that a PFC emulsion can significantly increase cerebral oxygenation after TBI and enhance mitochondrial function at 4 hours after injury as compared with saline. This study demonstrates a new therapeutic potential for PFC to enhance cerebral oxygenation and aerobic metabolism after TBI. However, the increased free radical formation with high-dose PFCs suggests the need for further studies combining PFCs with free radical scavengers.
Daugherty
Wilson P
WP
Departments of Neurosurgery and Physiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
Levasseur
Joseph E
JE
Sun
Dong
D
Spiess
Bruce D
BD
Bullock
M Ross
MR
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism*; D004655:Emulsions; D005466:Fluorocarbons / Q000494:pharmacology*; D006842:Hydrocarbons, Brominated; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects*; D010474:Percussion / Q000009:adverse effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D004655:Emulsions; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D017382:Reactive Oxygen Species; C003072:perflubron