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

Research output: Contribution to journalArticle

  • F Streijger
  • J H T Lee
  • G J Duncan
  • M T L Ng
  • P Assinck
  • T Bhatnagar
  • W T Plunet
  • W Tetzlaff
  • B K Kwon

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Original languageEnglish
Pages (from-to)870-83
Number of pages14
JournalJournal of Neuroscience Research
Issue number7
Early online date21 Mar 2014
Publication statusPublished - Jul 2014


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.

    Research areas

  • Animals, Benzenesulfonates, Biomechanical Phenomena, Complement C6/therapeutic use, Diet, Ketogenic/methods, Disease Models, Animal, Drug Therapy, Combination, Ghrelin/therapeutic use, Ibuprofen/therapeutic use, Male, Motor Activity/drug effects, Psychomotor Performance/drug effects, Rats, Rats, Sprague-Dawley, Recovery of Function/drug effects, Spinal Cord Injuries/diet therapy, Statistics, Nonparametric

ID: 133871392