Combinatorial treatment of acute spinal cord injury with ghrelin, ibuprofen, C16, and ketogenic diet does not result in improved histologic or functional outcome

Authors

  • F. Streijger,

    1. International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, British Columbia, Canada
    2. Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada
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    • F. Streijger and J.H.T. Lee contributed equally to this work.

  • J.H.T. Lee,

    1. International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, British Columbia, Canada
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    • F. Streijger and J.H.T. Lee contributed equally to this work.

  • G.J. Duncan,

    1. International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, British Columbia, Canada
    2. Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada
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  • M.T.L. Ng,

    1. International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, British Columbia, Canada
    2. Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada
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  • P. Assinck,

    1. International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, British Columbia, Canada
    2. Department of Neuroscience, University of British Columbia, Vancouver, British Columbia, Canada
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  • T. Bhatnagar,

    1. International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, British Columbia, Canada
    2. Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada
    3. Department of Mechanical Engineering, University of British Columbia, Vancouver, British Columbia, Canada
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  • W.T. Plunet,

    1. International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, British Columbia, Canada
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  • W. Tetzlaff,

    1. International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, British Columbia, Canada
    2. Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada
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  • B.K. Kwon

    Corresponding author
    1. International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, British Columbia, Canada
    2. Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada
    3. Combined Neurosurgical and Orthopaedic Spine Program (CNOSP), Department of Orthopaedics, University of British Columbia, Vancouver, British Columbia, Canada
    • Correspondence to: Brian K. Kwon, MD, PhD, FRCSC Associate Professor, Department of Orthopaedics, University of British Columbia, 6th Floor, Blusson Spinal Cord Center, VGH, 818 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1M9. E-mail: brian.kwon@vch.ca

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Abstract

Because of the complex, multifaceted nature of spinal cord injury (SCI), it is widely believed that a combination of approaches will be superior to individual treatments. Therefore, we employed a rat model of cervical SCI to evaluate the combination of four noninvasive treatments that individually have been reported to be effective for acute SCI during clinically relevant therapeutic time windows. These treatments included ghrelin, ibuprofen, C16, and ketogenic diet (KD). These were selected not only because of their previously reported efficacy in SCI models but also for their potentially different mechanisms of action. The administration of ghrelin, ibuprofen, C16, and KD several hours to days postinjury was based on previous observations by others that each treatment had profound effects on the pathophysiology and functional outcome following SCI. Here we showed that, with the exception of a modest improvement in performance on the Montoya staircase test at 8–10 weeks postinjury, the combinatorial treatment with ghrelin, ibuprofen, C16, and KD did not result in any significant improvements in the rearing test, grooming test, or horizontal ladder. Histologic analysis of the spinal cords did not reveal any significant differences in tissue sparing between treatment and control groups. Although single approaches of ghrelin, ibuprofen, C16, and KD have been reported to be beneficial after SCI, our results show that the combination of the four interventions did not confer significant functional or histological improvements in a cervical model of SCI. Possible interactions among the treatments may have negated their beneficial effects, emphasizing the challenges that have to be addressed when considering combinatorial drug therapies for SCI. © 2014 Wiley Periodicals, Inc.

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