Progress in dodecafluoropentane emulsion as a neuroprotective agent in a rabbit stroke model

Mol Neurobiol. 2013 Oct;48(2):363-7. doi: 10.1007/s12035-013-8495-6. Epub 2013 Jun 28.

Abstract

Dodecafluoropentane emulsion (DDFPe) in 250 nm nanodroplets seems to swell modestly to accept and carry large amounts of oxygen in the body at >29 °C. Small particle size allows oxygen delivery even into hypoxic tissue unreachable by erythrocytes. Using permanent cerebral embolic occlusion in rabbits, we assessed DDFPe dose response as a neuroprotectant at 7 and 24 h post-embolization without lysis of arterial obstructions and investigated blood pharmacokinetics. New Zealand White rabbits (N = 56) received cerebral angiography and embolic spheres (diameter = 700-900 μm) occluded middle and/or anterior cerebral arteries. Intravenous DDFPe dosing (2 % w/v emulsion) began at 60 min and repeated every 90 min until sacrifice at 7 or 24 h post-embolization. Seven-hour groups: (1) control (embolized without treatment, N = 6), and DDFPe treatment: (2) 0.1 ml/kg (N = 7), (3) 0.3 ml/kg (N = 9), (4) 0.6 ml/kg (N = 8). Twenty-four-hour groups: (5) control (N = 16), and DDFPe treatment: (6) 0.1 ml/kg (N = 10). Infarcts as percent of total brain volume were determined using vital stains on brain sections. Other alert normal rabbits (N = 8) received IV doses followed by rapid arterial blood sampling and GC-MS analysis. Percent infarct volume means significantly decreased for all DDFPe-treated groups compared with controls, p = <0.004 to <0.03. Blood DDFP (gas) half-life was 1.45 ± 0.17 min with R = 0.958. Mean blood clearance was 78.5 ± 24.9 ml/min/kg (mean ± SE). Intravenous DDFPe decreases ischemic stroke infarct volumes. Blood half-life values are very short. The much longer therapeutic effect, >90 min, suggests multiple compartments. Lowest effective dose and maximum effective therapy duration are not yet defined. Rapid development is warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / pathology
  • Cerebral Infarction / drug therapy*
  • Cerebral Infarction / pathology
  • Disease Models, Animal
  • Emulsions
  • Fluorocarbons / blood
  • Fluorocarbons / pharmacology
  • Fluorocarbons / therapeutic use*
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Rabbits
  • Stroke / drug therapy*
  • Stroke / pathology
  • Time Factors

Substances

  • Emulsions
  • Fluorocarbons
  • Neuroprotective Agents
  • perfluoropentane