Perfluorocarbon emulsion improves cerebral oxygenation and mitochondrial function after fluid percussion brain injury in rats

Neurosurgery. 2004 May;54(5):1223-30; discussion 1230. doi: 10.1227/01.neu.0000119238.68938.5d.

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% 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).

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Brain Injuries / etiology
  • Brain Injuries / metabolism*
  • Emulsions
  • Fluorocarbons / pharmacology*
  • Hydrocarbons, Brominated
  • Male
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Oxidation-Reduction / drug effects
  • Oxygen Consumption / drug effects*
  • Percussion / adverse effects
  • Rats
  • Reactive Oxygen Species / metabolism

Substances

  • Emulsions
  • Fluorocarbons
  • Hydrocarbons, Brominated
  • Reactive Oxygen Species
  • perflubron