Dodecafluoropentane Improves Neurological Function Following Anterior Ischemic Stroke

Abstract

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.

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Acknowledgments

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.

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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.

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Arthur, M.C., Brown, A., Carlson, K. et al. Dodecafluoropentane Improves Neurological Function Following Anterior Ischemic Stroke. Mol Neurobiol 54, 4764–4770 (2017). https://doi.org/10.1007/s12035-016-0019-8

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Keywords

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