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. WoodsEmail author
  • R. D. Skinner
  • A. M. Ricca
  • A. T. Brown
  • J. D. Lowery
  • M. J. Borrelli
  • J. O. Lay
  • W. C. Culp


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.


Dodecafluoropentane emulsion Neuroprotective agent Stroke model Rabbit 



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.


  1. 1.
    Kochanek K, Xu J, Murphy SL, Minino AM, Kung H-C (2011) Deaths: Final data for 2009. Natl Vital Stat Rep 60(3):1–117Google Scholar
  2. 2.
    Roger VL et al (2012) AHA statistical update: heart diseases and stroke statistics–2012 Update. Circulation 125:e2–e220, ePub Dec 15, 2011PubMedCrossRefGoogle Scholar
  3. 3.
    Saver JL, Jahan R, Levy EI, Jovin TG, Baxter B, Nogueira RG, Clark W, Budzik R, Zaidat OO, Trialists SWIFT (2012) Solitaire flow restoration device versus the Merci Retriever in patients with acute ischemic stroke (SWIFT): a randomized, parallel-group, non-inferiority trial (2012). Lancet 380(9849):1241–1249PubMedCrossRefGoogle Scholar
  4. 4.
    Donnan GA (2009) The 2007 Feinberg lecture: a new road map for neuroprotection. Stroke 39:242–248CrossRefGoogle Scholar
  5. 5.
    Diener HC, Lees KR, Lyden P, Grotta J, Davalos A, Davis SM, Shuaib A, Ashwood T, Wasiewski W, Alderfer V, Hardemart HG, Rodichok L, SAINT I and II Investigators (2008) NXY-059 for the treatment of acute stroke: pooled analysis of the SAINT I and II Trials. Stroke 39:1751–1758PubMedCrossRefGoogle Scholar
  6. 6.
    Heiss WD, Brainin M, Bornstein NM, Tuomilehto J, Hong Z, Cerebrolysin Acute Stroke Treatment in Asia (CASTA) Investigators (2012) Cerebrolysin in patients with acute ischemic stroke in Asia: result of a double-blind, placebo-controlled randomized trial. Stroke 43(3):630–636CrossRefGoogle Scholar
  7. 7.
    Johnson JLC, Dolezal MC, Kerschen A, Matsunaga TO, Unger EC (2009) In vitro comparison of dodecafluoropentane (DDFP), perfluorodecalin (PFD), and perfluoroctylbromide (PFOB) in the facilitation of oxygen exchange. Artif Cell Blood 37:156–162CrossRefGoogle Scholar
  8. 8.
    Culp WC, Woods SD, Skinner RD, Brown AT, Lowery JD, Johnson JLH, Unger EC, Hennings LJ, Borrelli MJ, Roberson PK (2012) Dodecafluoropentane emulsion decreases infarct volume in a rabbit ischemic stroke model. J Vasc Interv Radiol 23:116–121PubMedCrossRefGoogle Scholar
  9. 9.
    Correas JM, Quay SC (1996) EchoGen emulsion: a new ultrasound contrast agent based on phase shift colloids. Clin Radiol 51(S1):11–14PubMedGoogle Scholar
  10. 10.
    Culp WC, Woods SD, Brown AT, Lowery JD, Hennings LJ, Skinner RD, Borrelli MJ, Roberson PK. Three variations in rabbit angiographic stroke models. J Neurosci Meth, Epub ahead of print Nov 8 2012, doi: 10.1016/j/jneurometh.2012.10.107
  11. 11.
    Reiss JG (2005) Understanding the fundamentals of perfluorocarbons and perfluorocarbon emulsions relevant to in vivo oxygen delivery. Artif Cells Blood Substit Immobil Biotechnol 33:47–63CrossRefGoogle Scholar
  12. 12.
    Remy B, Deby-Dupont G, Lamy M (1999) Red blood cell substitutes: fluorocarbon emulsions and haemoglobin solutions. Br Med Bull 55:277–298PubMedCrossRefGoogle Scholar
  13. 13.
    The European Agency for the Evaluation of Medicinal Products Human Medicines Evaluation Unit, 27 July 1998, CPMP/1342/98Google Scholar
  14. 14.
    Lundgren CEG, Bergoe GW, Tyssebotn IM (2006) Intravascular fluorocarbon-stabilized microbubbles protect against fatal anemia in rats. Artif Cell Blood Sub 34:473–486CrossRefGoogle Scholar
  15. 15.
    Tyssebotn IM, Lundgren CE, Olszowka AJ, Bergoe GW (2010) Hypoxia due to shunts in pig lung treated with O2 and fluorocarbon-derived intravascular microbubbles. Artif Cells Substit Immobil Biotechnol 38(2):79–89CrossRefGoogle Scholar
  16. 16.
    Grayburn PA, Erickson JM, Excobar J, Womack L, Velasco CE (1995) Peripheral intravenous myocardial contrast echocardiography using a 2% dodecafluoropentane emulsion: identification of myocardial risk area and infarct size in the canine model of ischemia. J Am Coll Cardiol 26(5):1340–1347PubMedCrossRefGoogle Scholar
  17. 17.
    Khor SP (2012) Amendment to the pharmacokinetic analysis of clinical data from study SON-3600-1004a: NuvOx Formal Study ReportGoogle Scholar
  18. 18.
    Correas JM, Meuter AR, Singlas E, Kessler DR, Worah D, Quay SC (2001) Human pharmacokinetics of a perfluorocarbon ultrasound contrast agent evaluated with gas chromatography. Ultrasound Med Biol 27:565–570PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • S. D. Woods
    • 1
    Email author
  • 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

Personalised recommendations