Acute Delivery of EphA4-Fc Improves Functional Recovery after Contusive Spinal Cord Injury in Rats

• DOI: 10.1089/neu.2012.2729
• Publication Date: 2013-04-04T11:53:02Z
• Authors: Mark Damien Spane...; Sophie Ines Tajouri; Cornel Mirciov; Nyoman Kurniawan; Martin John Pearse; Louis Jerry Fabri; Catherine Mary Ow...; Matthew Philip Hardy; Rebecca Anne Brad...; Melanie Louise Ra...; Ann Maree Turnley; Marc Jan Ruitenberg; Andrew Wallace Boyd; Perry Francis Bar...
• Keywords: Recombinant Fusion Proteins; Blotting, Western; 610; EphA4; Enzyme-Linked Immunosorbent Assay; Spinal cord injury; Transfection; 03 medical and health sciences; Magnetic resonance imaging; 0302 clinical medicine; Animals; Humans; Rats, Wistar; Spinal Cord Injuries; Receptor, EphA4; Brain; Recovery of Function; Magnetic Resonance Imaging; Immunoglobulin Fc Fragments; Rats; Disease Models, Animal; Female; 2728 Clinical Neurology; Neurotrauma

Blocking the action of inhibitory molecules at sites of central nervous system injury has been proposed as a strategy to promote axonal regeneration and functional recovery. We have previously shown that genetic deletion or competitive antagonism of EphA4 receptor activity promotes axonal regeneration and functional recovery in a mouse model of lateral hemisection spinal cord injury. Here we have assessed the effect of blocking EphA4 activation using the competitive antagonist EphA4-Fc in a rat model of thoracic contusive spinal cord injury. Using a ledged tapered balance beam and open-field testing, we observed significant improvements in recovery of locomotor function after EphA4-Fc treatment. Consistent with functional improvement, using high-resolution ex vivo magnetic resonance imaging at 16.4T, we found that rats treated with EphA4-Fc had a significantly increased cross-sectional area of the dorsal funiculus caudal to the injury epicenter compared with controls. Our findings indicate that EphA4-Fc promotes functional recovery following contusive spinal cord injury and provides further support for the therapeutic benefit of treatment with the competitive antagonist in acute cases of spinal cord injury.