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Magnesium enhances the beneficial effects of NK1 antagonist administration on blood-brain barrier permeability and motor outcome after traumatic brain injury.

Abstract
The current study investigated whether adding magnesium to an NK1 tachykinin receptor antagonist after traumatic brain injury would enhance efficacy to further reduce blood-brain barrier permeability and improve functional recovery compared to either treatment alone. Sprague-Dawley rats were injured using the impact acceleration model of diffuse brain injury, and received either no treatment, MgSO4 (30 mg/kg IV), the NK1 antagonist n-acetyl L tryptophan (2.5 mg/kg IP), or both agents combined. Animals were then killed at either 1, 5, or 24 h postinjury for determination of blood-brain barrier permeability using previously administered Evans blue dye or assessed for functional outcome over a 1-week period using the rotarod motor test. As expected, both MgSO4 and n-acetyl L tryptophan significantly reduced blood-brain barrier permeability and improved functional outcome. However, combined n-acetyl L tryptophan and MgSO4 was more effective at reducing blood-brain barrier permeability (P < 0.05) and improving functional outcome (P < 0.001) compared to the individual compounds. Our results demonstrate that combination therapy with magnesium and an NK1 antagonist may be a more effective therapy for TBI than either compound administered alone.
AuthorsJoshua L Ameliorate, Mounir N Ghabriel, Robert Vink
JournalMagnesium research (Magnes Res) Vol. 30 Issue 3 Pg. 88-97 (Aug 01 2017) ISSN: 1952-4021 [Electronic] England
PMID29256408 (Publication Type: Journal Article)
Chemical References
  • Receptors, Tachykinin
  • Substance P
  • N-acetyltryptophan
  • Magnesium Sulfate
  • Tryptophan
  • Magnesium
Topics
  • Animals
  • Blood-Brain Barrier (drug effects, metabolism)
  • Brain Injuries, Traumatic (drug therapy, metabolism)
  • Magnesium (pharmacology, therapeutic use)
  • Magnesium Sulfate (pharmacology, therapeutic use)
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Tachykinin (antagonists & inhibitors)
  • Recovery of Function
  • Substance P (metabolism)
  • Tryptophan (analogs & derivatives, therapeutic use)

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