Early administration of a second-generation perfluorochemical decreases ischemic brain damage in a model of permanent middle cerebral artery occlusion in the rat

Neurol Res. 2005 Jul;27(5):509-15. doi: 10.1179/016164105X15677.

Abstract

Objectives: Perfluorochemicals (PFCs) may exert a neuroprotective function in the early phase of ischemia by improving the oxygen supply to the endangered tissue. We have, therefore, investigated the effect of Oxycyte, a second-generation perfluorocarbon solution, on the extent of early ischemic brain damage in a model of permanent focal cerebral ischemia.

Methods: Eight hours of permanent focal cerebral ischemia was induced in isoflurane anesthetized male Sprague-Dawley rats by unilateral middle cerebral artery (MCA) thread occlusion under the control of laser Doppler flowmetry (LDF). Animals were assigned to one of the following treatment groups: nO2-NaCl and hO2-NaCl-NaCl (0.9%, 1 ml/100 g i.v.) and nO2-Oxycyte and hO2-Oxycyte-Oxycyte (1 ml/100 g i.v.). The injection of NaCl or Oxycyte was performed immediately after MCA occlusion. After injection, breathing was changed to pure oxygen in groups hO2-NaCl and hO2-Oxycyte while animals in groups nO2-NaCl and nO2-Oxycyte were allowed to breathe air. The necrotic volume was calculated from serial coronal sections stained with silver-nitrate. In addition, nitrotyrosine production was studied by immunohistochemistry.

Results: Upon MCA occlusion, animals showed a reduction of cerebral blood flow of approximately 80% of the LDF signal in all groups. Hemodynamic and metabolic parameters were not affected by the infusion of Oxycyte. The total infarct volume was reduced in hO2-Oxycyte animals [group nO2-NaCl: 341+/-31 mm3 (mean+/-SD), group hO2-NaCl: 351+/-33 mm3, group nO2-Oxycyte: 354+/-24 mm3, and group hO2-Oxycyte: 300+/-29 mm3, p < 0.05 versus all other groups]. Moreover, hO2-Oxycyte animals showed lesser intensity of nitrotyrosine staining when compared with hO2-NaCl animals.

Discussion: These results suggest that Oxycyte administered immediately after the onset of vascular occlusion may exert neuroprotective effects in the early phase of brain ischemia.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Blood Gas Analysis / methods
  • Brain Ischemia / etiology
  • Brain Ischemia / pathology
  • Brain Ischemia / prevention & control*
  • Cerebrovascular Circulation / drug effects
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Fluorocarbons / therapeutic use*
  • Immunohistochemistry / methods
  • Infarction, Middle Cerebral Artery / complications
  • Infarction, Middle Cerebral Artery / pathology
  • Laser-Doppler Flowmetry / methods
  • Male
  • Necrosis / metabolism
  • Necrosis / pathology
  • Necrosis / prevention & control
  • Neuroprotective Agents / therapeutic use*
  • Oxygen / therapeutic use*
  • Peroxynitrous Acid
  • Rats
  • Rats, Sprague-Dawley
  • Silver Staining / methods
  • Time Factors
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism

Substances

  • Fluorocarbons
  • Neuroprotective Agents
  • Peroxynitrous Acid
  • 3-nitrotyrosine
  • Tyrosine
  • Oxygen