Dodecafluoropentane Improves Neurological Function Following Anterior Ischemic Stroke


Dodecafluoropentane emulsion (DDFPe), an advanced oxygen transport drug, given IV at 90-min intervals maintains viability in the penumbra during cerebral ischemia in the standard rabbit anterior stroke model (STND). This study investigated shortened dosage schedules of DDFPe in nonstandard posterior (NSTND) strokes following occlusions of the posterior cerebral arteries. DDFPe given at shortened schedules of 30 or 60-min injection intervals will reduce neurological deficits, percent stroke volume (%SV), and serum glutamate levels in NSTND ischemic strokes. New Zealand White rabbits (N = 26) were randomly placed into three groups: A (n = 9) controls given saline injections every 60 min, B (n = 9) 2 % DDFPe given IV every 30 min, and C (n = 8) DDFPe every 60 min. Injections began 1 h after embolization. Groups were subdivided into STND and NSTND based on angiographically verified embolization of the cerebral arteries. Neurological assessments and blood samples were done at 0.5–1-h intervals. Rabbits were euthanized at 7 h following embolization. Stained brain slices were measured for %SV. The 30 and 60-min subgroups did not differ and were combined as DDFPe-STND or DDFPe-NSTND groups. In the DDFPe-STND stroke group, the %SV, neurological assessment scores (NAS), and serum glutamate were decreased vs. STND controls (p = 0.0016, 0.008, and 0.016, respectively). In the DDFPe-NSTND stroke group, %SV, NAS, and serum glutamate did not differ statistically compared to NSTND controls (p = 0.82, 0.097, and 0.06, respectively). More frequent dosage schedules provided no additional improvement. In anterior strokes, DDFPe improves recovery but not in the more severe NSTND strokes.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. 1.

    del Zoppo G, Saver J, EC J, et al. (2009) Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator. A science advisory from the American Heart Association/American Stroke Association. Stroke 40:2945–2948. doi:10.1161/STROKEAHA.109.192535

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Mozaffarian D, Benjamin EJ, Go AS, et al. (2015) Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circ 131:e29–322. doi:10.1161/CIR.0000000000000152

    Article  Google Scholar 

  3. 3.

    Woods SD, Skinner RD, Ricca AM, Brown AT, et al. (2013) Progress in dodecafluoropentane emulsion as a neuroprotective agent in a rabbit stroke model. Mol Neurobiol 48:363–367. doi:10.1007/s12035-013-8495-6

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Culp WC, Woods SD, Skinner RD, Brown AT, et al. (2012) Dodecafluoropentane emulsion decreases infarct volume in a rabbit ischemic stroke model. JVIR 23:116–121. doi:10.1016/j.jvir.2011.10.001

    Article  PubMed  Google Scholar 

  5. 5.

    Johnson JL, Dolezal MC, Kerschen A, Matsunaga TO, et al. (2009) In vitro comparison of dodecafluoropentane (DDFP) perfluorodecalin (PFD), and perfluoroctylbromide (PFOB) in the facilitation of oxygen exchange. Artif Cell Blood 37:156–162. doi:10.1080/10731190903043192

    CAS  Article  Google Scholar 

  6. 6.

    Culp WC, Flores R, Brown AT, Lowery JD, et al. (2011) Successful microbubble sonothrombolysis without tissue plasminogen activator in a rabbit model of acute ischemic stroke. Stroke 42:2280–2285. doi:10.1161/STROKEAHA.110.607150

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Brown AT, Skinner RD, Flores R, Hennings L, et al. (2010) Stroke location and brain function in an embolic rabbit stroke model. JVIR 21:903–909. doi:10.1016/j.jvir.2010.02.023

    Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Flores R, Lowery J, Skinner RD, Roberson PK, et al. (2011) Transcutaneous therapeutic ultrasound reduces infarct size in a rabbit model of acute insoluble ischemic stroke. J Exp Stroke Transl Med 4:1–7 SFES 1939-067X/10

    Article  Google Scholar 

  9. 9.

    Brown AT, Flores R, Hamilton E, Roberson PK, et al. (2011) Microbubbles improve sonothrombolysis in vitro and decrease hemorrhage in vivo in a rabbit stroke model. Investig Radiol 46:202–207. doi:10.1097/RLI.0b013e318200757a

    Article  Google Scholar 

  10. 10.

    Flores R, Hennings LJ, Lowery JD, Brown AT, et al. (2011) Microbubble-augmented ultrasound sonothrombolysis decreases intracranial hemorrhage in a rabbit model of acute ischemic stroke. Investig Radiol 46:419–424. doi:10.1097/RLI.0b013e31820e143a

    CAS  Article  Google Scholar 

  11. 11.

    Culp WC, Woods SD, Brown AT, Lowery JD, et al. (2012) Three variations in rabbit angiographic stroke models. J Neurosci Methods 212:322–328. doi:10.1016/j.jneumeth.2012.10.017

    Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Brown A, Woods S, Skinner R, Hatton J, et al. (2013) Neurological assessment scores in rabbit embolic stroke models. Open Neurol J 7:38–43

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Zhao BQ, Suzuki Y, Kondo K, Kawano K, et al. (2001) Cerebral hemorrhage due to heparin limits its neuroprotective effects: studies in a rabbit model of photothrombotic middle cerebral artery occlusion. Brain Res 902:30–39

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Zhao BQ, Suzuki Y, Kondo K, Kawano K, et al. (2002) A novel MCA occlusion model of photothrombotic ischemia with cyclic flow reductions: development of cerebral hemorrhage induced by heparin. Brain Res Protocol 9:85–92

    CAS  Article  Google Scholar 

  15. 15.

    Zhao BQ, Suzuki Y, Kondo K, Ikeda Y, et al. (2001) Combination of a free radical scavenger and heparin reduces cerebral hemorrhage after heparin treatment in a rabbit middle cerebral artery occlusion model. Stroke 32:2157–2163

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Chen ZZ, Jiang XD, Zhang LL, Shang JH, et al. (2008) Beneficial effect of autologous transplantation of bone marrow stromal cells and endothelial progenitor cells on cerebral ischemia in rabbits. Neurosci Lett 445:36–41

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Mehndiratta M, Pandey S, Nayak R, Alam A (2012) Posterior circulation ischemic stroke—clinical characteristics, risk factors, and subtypes in a north Indian population—a prospective study. Neurohospitalist 2:46–50. doi:10.1177/1941874412438902

    Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Dorňák T, Kral M, Hazlinger M, Herzog R, et al. (2015) Posterior vs. anterior circulation infarction: demography, outcomes, and frequency of hemorrhage after thrombolysis. Int J of Stroke 10:1224–1228. doi:10.1111/ijs.12626

    Google Scholar 

  19. 19.

    Boulos AS, Deshaies EM, Dalfino JC, Feustel PJ, et al. (2011) Tamoxifen as an effective neuroprotectant in an endovascular canine model of stroke. J Neurosurg 114:1117–1126. doi:10.3171/2010.8.JNS09352

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Ohishi H, Nishijima M, Ogawa A, Yoshimoto T, et al. (1984) Protective effect of mannitol in cerebral infarction—CT findings and physiological observation in experimental cerebral infarction in dogs. No Shinkei Geka 12:153–158

    CAS  PubMed  Google Scholar 

  21. 21.

    Saver JL, Starkman S, Eckstein M, Stratton SJ, et al. (2015) Prehospital use of magnesium sulfate as neuroprotection in acute stroke. N Engl J Med 372:528–536. doi:10.1056/NEJMoa1408827

    Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Culp WC, Brown AT, Lowery JD, Arthur MC, et al. (2015) Dodecafluoropentane emulsion extends window for tPA therapy in a rabbit stroke model. Mol Neurobiol 52:979–984. doi:10.1007/s12035-015-9243-x

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Aliprandi A, Longoni M, Stanzani L, Tremolizzo L, et al. (2005) Increased plasma glutamate in stroke patients might be linked to altered platelet release and uptake. J Cereb Blood Flow Metab 25:513–519

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Godino M, Lizasoain I, Sanchez-Prieto J (2013) Amelioration of ischemic brain damage by peritoneal dialysis. J Clin Invest 123:4359–4363. doi:10.1172/JCI67284

    CAS  Article  PubMed Central  Google Scholar 

Download references


Author Contributions Statement

AB conceived the study and designed the data collection. AB obtained research funding. MCA, JL, KC, and AB collected the data. MCA, RDS, WCC, and AB provided statistical advice on study design and analyzed the data. MCA, KC, WCC, and AB drafted the manuscript, and all authors contributed to its revision.

Author information



Corresponding author

Correspondence to Aliza Brown.

Ethics declarations

All animal procedures were approved by the Institutional Care and Use Committee.

Sources of Funding

This project was supported by the Fund to Cure Stroke, a grant fund of the University of Arkansas for Medical Sciences Foundation (to author AB) and by the NIGMS IDeA Award P30 GM110702 (sponsoring author AB).

Conflict of Interest

A patent has been applied for the use of dodecafluoropentane for stroke therapy by authors WCC and RDS.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Arthur, M.C., Brown, A., Carlson, K. et al. Dodecafluoropentane Improves Neurological Function Following Anterior Ischemic Stroke. Mol Neurobiol 54, 4764–4770 (2017).

Download citation


  • Stroke
  • DDFPe
  • Rabbit
  • Ischemia
  • Tissue plasminogen activator
  • Neurological assessment score