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The Evaluation of Magnesium Chloride within a Polyethylene Glycol Formulation in a Porcine Model of Acute Spinal Cord Injury
- Source :
- Brain and Mind Institute Researchers' Publications
- Publication Year :
- 2016
-
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.
- Subjects :
- 0301 basic medicine
Swine
medicine.medical_treatment
Drug Compounding
Drug Evaluation, Preclinical
Magnesium Chloride
Polyethylene glycol
Neuroprotection
Thoracic Vertebrae
Polyethylene Glycols
03 medical and health sciences
chemistry.chemical_compound
Random Allocation
0302 clinical medicine
Injury Site
medicine
Psychology
Animals
Spinal cord injury
Saline
Miniature
Spinal Cord Injuries
medicine.diagnostic_test
Animal
business.industry
Neurosciences
Magnetic resonance imaging
Recovery of Function
medicine.disease
Preclinical
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
chemistry
Anesthesia
Disease Models
Thoracic vertebrae
Acute Disease
Drug Evaluation
Swine, Miniature
Female
Neurology (clinical)
business
030217 neurology & neurosurgery
Ex vivo
Locomotion
Subjects
Details
- ISSN :
- 15579042
- Volume :
- 33
- Issue :
- 24
- Database :
- OpenAIRE
- Journal :
- Journal of neurotrauma
- Accession number :
- edsair.doi.dedup.....f81dd79afb92c7fab1db986a4857ea9d