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Molecular Neurobiology

, Volume 48, Issue 2, pp 363–367 | Cite as

Progress in Dodecafluoropentane Emulsion as a Neuroprotective Agent in a Rabbit Stroke Model

  • S. D. Woods
  • R. D. Skinner
  • A. M. Ricca
  • A. T. Brown
  • J. D. Lowery
  • M. J. Borrelli
  • J. O. Lay
  • W. C. Culp
Article

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.

Keywords

Dodecafluoropentane emulsion Neuroprotective agent Stroke model Rabbit 

Notes

Acknowledgments

This study was supported by the Hornick Fund for stroke research from UAMS.

Conflict of interest

WC Culp and RD Skinner have an application pending to the USPTC regarding the use of DDFPe in numerous medical situations.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • S. D. Woods
    • 1
  • R. D. Skinner
    • 1
    • 2
  • A. M. Ricca
    • 1
  • A. T. Brown
    • 1
  • J. D. Lowery
    • 3
  • M. J. Borrelli
    • 1
  • J. O. Lay
    • 4
  • W. C. Culp
    • 1
  1. 1.Department of RadiologyUniversity of Arkansas for Medical Sciences (UAMS)Little RockUSA
  2. 2.Department of Neurobiology and Developmental SciencesUniversity of Arkansas for Medical Sciences (UAMS)Little RockUSA
  3. 3.Department of Laboratory Animal MedicineUniversity of Arkansas for Medical Sciences (UAMS)Little RockUSA
  4. 4.Department of ChemistryUniversity of Arkansas at FayettevilleFayettevilleUSA

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