Perfluorocarbon Emulsion Improves Cerebral Oxygenation and Mitochondrial Function after Fluid Percussion Brain Injury in Rats

Wilson P. Daugherty, Joseph E. Levasseur, Dong Sun, Bruce D. Spiess, Ross Bullock, E. Sander Connolly, Charles J. Hodge, R. Loch Macdonald

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1223-1230
Number of pages8
JournalNeurosurgery
Volume54
Issue number5
StatePublished - May 1 2004
Externally publishedYes

Fingerprint

Percussion
Fluorocarbons
Emulsions
Brain Injuries
Wounds and Injuries
Oxidation-Reduction
Free Radicals
Oxygen
Free Radical Scavengers
Peroxynitrous Acid
Peroxides
Brain Ischemia
Respiration
Theoretical Models
Coloring Agents
Ischemia
Stroke

Keywords

  • Cerebral oxygenation
  • Mitochondrial function
  • Perfluorocarbon
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Daugherty, W. P., Levasseur, J. E., Sun, D., Spiess, B. D., Bullock, R., Connolly, E. S., ... Macdonald, R. L. (2004). Perfluorocarbon Emulsion Improves Cerebral Oxygenation and Mitochondrial Function after Fluid Percussion Brain Injury in Rats. Neurosurgery, 54(5), 1223-1230.

Perfluorocarbon Emulsion Improves Cerebral Oxygenation and Mitochondrial Function after Fluid Percussion Brain Injury in Rats. / Daugherty, Wilson P.; Levasseur, Joseph E.; Sun, Dong; Spiess, Bruce D.; Bullock, Ross; Connolly, E. Sander; Hodge, Charles J.; Macdonald, R. Loch.

In: Neurosurgery, Vol. 54, No. 5, 01.05.2004, p. 1223-1230.

Research output: Contribution to journalArticle

Daugherty, WP, Levasseur, JE, Sun, D, Spiess, BD, Bullock, R, Connolly, ES, Hodge, CJ & Macdonald, RL 2004, 'Perfluorocarbon Emulsion Improves Cerebral Oxygenation and Mitochondrial Function after Fluid Percussion Brain Injury in Rats', Neurosurgery, vol. 54, no. 5, pp. 1223-1230.
Daugherty WP, Levasseur JE, Sun D, Spiess BD, Bullock R, Connolly ES et al. Perfluorocarbon Emulsion Improves Cerebral Oxygenation and Mitochondrial Function after Fluid Percussion Brain Injury in Rats. Neurosurgery. 2004 May 1;54(5):1223-1230.
Daugherty, Wilson P. ; Levasseur, Joseph E. ; Sun, Dong ; Spiess, Bruce D. ; Bullock, Ross ; Connolly, E. Sander ; Hodge, Charles J. ; Macdonald, R. Loch. / Perfluorocarbon Emulsion Improves Cerebral Oxygenation and Mitochondrial Function after Fluid Percussion Brain Injury in Rats. In: Neurosurgery. 2004 ; Vol. 54, No. 5. pp. 1223-1230.
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abstract = "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.",
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AU - Spiess, Bruce D.

AU - Bullock, Ross

AU - Connolly, E. Sander

AU - Hodge, Charles J.

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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.

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