Resident University of Maryland School of Medicine Baltimore, MD, US
Introduction: Spinal cord injuries (SCI) occur in 0.9 per million annually and often result in severe neurological deficits. Maladaptive uptake of sodium and calcium drives delayed axon degeneration, which contributes to worsened outcomes. While several pharmacological sodium and calcium channel blockers have been studied, none have been translated to widespread clinical use, and most primarily block a single channel. Amiodarone, an FDA-approved class III antiarrhythmic drug, is a broad inhibitor of multiple sodium, calcium, and potassium channels and transporters, crosses the blood-brain barrier, is neuroprotective in animal models of ischemic stroke, and is well tolerated during brief treatment periods. Here, we sought to determine if amiodarone could be repurposed to improve locomotor function and reduce white matter degeneration in a mouse model of thoracic spinal cord injury.
Methods: Unilateral thoracic spinal cord contusions were performed in mice with a modified NYU impactor. Amiodarone was administered after injury (50 mg/kg IP loading dose followed by 25 mg/kg IP daily for 6 days). Mice were maintained for 4 weeks and locomotor function was assessed with modified Basso motor score (mBMS), inclined plane test (IPT), and accelerating rotarod (AR). Spinal cord atrophy was assessed with wet weight measurements of 15 mm spinal cord segments and in stained Paraffin sections.
Results: Mice treated with amiodarone had improved locomotor function versus vehicle (4 week contralateral mBMS: 1.25 vehicle vs 8.66 amio; IPT: 46.25 degrees vehicle vs 55.0 amio; AR: 15.5 seconds vehicle vs 50.6 amio; all p< 0.05). Compared to sham, SCI mice treated with vehicle had loss of cord wet weight and loss of white matter in paraffin sections. Amiodarone treatment prevented loss of cord wet weight (51.3 mg sham vs 43.2 vehicle vs 52.7 amio; p< 0.05) and helped to preserve white matter in sectioned cords.
Conclusion : Amiodarone improved locomotor function and reduced spinal cord atrophy in a mouse model of thoracic spinal cord injury. While further work is needed, our data suggest that amiodarone could be repurposed to treat patients with spinal cord injury.
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