Title

The Evaluation of Magnesium Chloride within a Polyethylene Glycol Formulation in a Porcine Model of Acute Spinal Cord Injury.

Authors

Femke Streijger, International Collaboration on Repair Discoveries (ICORD), University of British Columbia , Blusson Spinal Cord Center, Vancouver, British Columbia, Canada
Jae H T Lee, International Collaboration on Repair Discoveries (ICORD), University of British Columbia , Blusson Spinal Cord Center, Vancouver, British Columbia, Canada
Neda Manouchehri, International Collaboration on Repair Discoveries (ICORD), University of British Columbia , Blusson Spinal Cord Center, Vancouver, British Columbia, Canada
Elena B Okon, International Collaboration on Repair Discoveries (ICORD), University of British Columbia , Blusson Spinal Cord Center, Vancouver, British Columbia, Canada
Seth Tigchelaar, International Collaboration on Repair Discoveries (ICORD), University of British Columbia , Blusson Spinal Cord Center, Vancouver, British Columbia, Canada
Lisa M Anderson
Greg A Dekaban, Robarts Research Institute, Western University , London, Ontario, Canada
David A Rudko, Brain Imaging Center, Montreal Neurological Hospital and Institute , Montreal, Quebec, Canada
Ravi S Menon, Center for Functional and Metabolic Mapping, the University of Western Ontario , London, Ontario, Canada
Jennifer F Iaci, Acorda Therapeutics Inc. , Ardsley, New York
Donald C Button, Acorda Therapeutics Inc. , Ardsley, New York
Andrea M Vecchione, Acorda Therapeutics Inc. , Ardsley, New York
Andrey Konovalov, Acorda Therapeutics Inc. , Ardsley, New York
Patrick D Sarmiere, Acorda Therapeutics Inc. , Ardsley, New York
Chi Ung, Acorda Therapeutics Inc. , Ardsley, New York
Anthony O Caggiano, Acorda Therapeutics Inc. , Ardsley, New York
Brian K Kwon, International Collaboration on Repair Discoveries (ICORD), University of British Columbia , Blusson Spinal Cord Center, Vancouver, British Columbia, Canada & Department of Orthopedics, Vancouver Spine Surgery Institute, University of British Columbia , Blusson Spinal Cord Center, Vancouver, British Columbia, Canada

Document Type

Article

Publication Date

12-15-2016

Journal

Journal of neurotrauma

Volume

33

Issue

24

First Page

2202

Last Page

2216

URL with Digital Object Identifier

10.1089/neu.2016.4439

Abstract

A porcine model of spinal cord injury (SCI) was used to evaluate the neuroprotective effects of magnesium chloride (MgCl2) within a polyethylene glycol (PEG) formulation, called "AC105" (Acorda Therapeutics Inc., Ardsley, NY). Specifically, we tested the hypothesis that AC105 would lead to greater tissue sparing at the injury site and improved behavioral outcome when delivered in a clinically realistic time window post-injury. Four hours after contusion/compression injury, Yucatan minipigs were randomized to receive a 30-min intravenous infusion of AC105, magnesium sulfate (MgSO4), or saline. Animals received 4 additional infusions of the same dose at 6-h intervals. Behavioral recovery was tested for 12 weeks using two-dimensional (2D) kinematics during weight-supported treadmill walking and the Porcine Injury Behavior Scale (PTIBS), a 10-point locomotion scale. Spinal cords were evaluated ex vivo by diffusion-weighted magnetic resonance imaging (MRI) and subjected to histological analysis. Treatment with AC105 or MgSO4 did not result in improvements in locomotor recovery on the PTIBS or in 2D kinematics on weight-supported treadmill walking. Diffusion weighted imaging (DWI) showed severe loss of tissue integrity at the impact site, with decreased fractional anisotropy and increased mean diffusivity; this was not improved with AC105 or MgSO4 treatment. Histological analysis revealed no significant increase in gray or white matter sparing with AC105 or MgSO4 treatment. Finally, AC105 did not result in higher Mg2+ levels in CSF than with the use of standard MgSO4. In summary, when testing AC105 in a porcine model of SCI, we were unable to reproduce the promising therapeutic benefits observed previously in less-severe rodent models of SCI.

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