TY - JOUR
T1 - Perfluorocarbon Emulsion Improves Cerebral Oxygenation and Mitochondrial Function after Fluid Percussion Brain Injury in Rats
AU - Daugherty, Wilson P.
AU - Levasseur, Joseph E.
AU - Sun, Dong
AU - Spiess, Bruce D.
AU - Bullock, M. Ross
AU - Connolly, E. Sander
AU - Hodge, Charles J.
AU - Macdonald, R. Loch
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2004/5
Y1 - 2004/5
N2 - 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% O2, 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). CONCLUSION: 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.
AB - 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% O2, 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). CONCLUSION: 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.
KW - Cerebral oxygenation
KW - Mitochondrial function
KW - Perfluorocarbon
KW - Traumatic brain injury
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U2 - 10.1227/01.NEU.0000119238.68938.5D
DO - 10.1227/01.NEU.0000119238.68938.5D
M3 - Article
C2 - 15113478
AN - SCOPUS:2342655057
VL - 54
SP - 1223
EP - 1230
JO - Neurosurgery
JF - Neurosurgery
SN - 0148-396X
IS - 5
ER -