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Pharmacological neuroprotection in cervical spinal cord injury

University of British Columbia

Spinal cord injury (SCI) is a devastating condition that causes paralysis below the level of the injury. To date, there is no convincingly effective treatment. An enormous preclinical and clinical effort is underway to find a treatment, and one approach is to search for pharmacological agents that are already in clinical use (albeit for different indications), but that may also have neuroprotective properties. Examples of such drugs are magnesium, Riluzole (sodium channel blocker), minocycline and statins. While the majority of human SCI occur in the cervical spinal cord, the vast majority of laboratory SCI research employs animal models of thoracic SCI. An important step, therefore, in the preclinical evaluation of novel treatments is to assess their efficacy in a model of cervical SCI. First, I describe the development of a novel unilateral contusive model of cervical SCI with refined biomechanical, functional, and histological parameters using the Infinite Horizon spinal cord injury device. I conducted a series of experiments in which the spinal cord was injured using various impact forces, impact trajectories, and impact locations off the midline. Behavioral deficits were assessed using a variety of forelimb function tests, after which the cords were evaluated histologically. From these series of experiments, I established a new cervical unilateral spinal cord injury contusion model. Next, I evaluated the neuroprotective effects of minocycline and simvastatin in the clinically relevant unilateral cervical contusion model. Minocycline is a commonly prescribed tetracycline antibiotic that is prescribed for acne. Simvastatin is one of many hydroxymethylglutaryl-coenzyme-A reductase inhibitors that lower cholesterol. As both drugs have translational potential and have been reported to have neuroprotective properties in various neurological diseases, I assessed the neuroprotective effects of these drugs using a host of functional and histological assessments. In the end, there were no neurological improvements with minocycline or simvastatin treatment after a cervical contusion injury.

Text

2010-08-11

Attribution-NonCommercial-NoDerivs 3.0 Unported

http://hdl.handle.net/2429/27239

Zoology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/3.0/