Magnesium chloride in a polyethylene glycol formulation as a neuroprotective therapy for acute spinal cord injury: Preclinical refinement and optimization

Brian K. Kwon, Josee Roy, Jae H.T. Lee, Elena Okon, Hongbin Zhang, Jeffrey C. Marx, Mark S. Kindy

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Intravenously administered magnesium has been extensively investigated as a neuroprotective agent traumatic brain injuries and stroke. Numerous investigators have reported the neuroprotective benefits of magnesium in animal models of spinal cord injury (SCI) as well, but typically with doses that far exceed human tolerability. To develop magnesium into a clinically relevant therapy for SCI, further refinement and improvement of the magnesium formulation is necessary. In this series of experiments, we evaluated the neuroprotective efficacy of magnesium in a polyethylene glycol (PEG) formulation using an acute model of thoracic SCI. Following thoracic contusion (Infinite Horizon) rat SCI model, we independently confirmed the neuroprotective efficacy of the magnesium and PEG combination which had been previously reported in a thoracic clip compression model of SCI (Ditor et al., 2007). We established that the 254 μmol/kg dose of MgCl2 was superior to 127 μmol/kg MgCl 2 with respect to tissue sparing and locomotor recovery. Additionally, the number of infusions (2, 4, or 6), time between infusions (6 vs 8 hours), and different magnesium salts (MgCl2 vs MgSO4) were evaluated to determine an "optimal" treatment regimen. We observed that an "optimized" regimen of MgCl2 within PEG conferred greater tissue neuroprotection and improved locomotor recovery compared to methylprednisolone. Further a 4 hour time window of histologic and behavioral efficacy was established. The goal of these experiments was to help guide the treatment parameters for a clinical trial of magnesium within a polyethylene glycol formulation in acute human spinal cord injury.

Original languageEnglish
Pages (from-to)1379-1393
Number of pages15
JournalJournal of Neurotrauma
Volume26
Issue number8
DOIs
StatePublished - Aug 1 2009

Keywords

  • Magnesium chloride
  • Neuroprotection
  • Polyethylene glycol
  • Spinal cord injury

ASJC Scopus subject areas

  • Clinical Neurology

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