Acute delivery of EphA4-Fc improves functional recovery after contusive spinal cord injury in rats.

Abstract

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.

• Authors: Mark Damien Spanevello, Sophie Ines Tajouri, Cornel Mirciov, Nyoman Kurniawan, Martin John Pearse, Louis Jerry Fabri, Catherine Mary Owczarek, Matthew Philip Hardy, Rebecca Anne Bradford, Melanie Louise Ramunno, Ann Maree Turnley, Marc Jan Ruitenberg, Andrew Wallace Boyd, Perry Francis Bartlett
• Journal: Journal of neurotrauma (J Neurotrauma) Vol. 30 Issue 12 Pg. 1023-34 (Jun 15 2013) ISSN: 1557-9042 [Electronic] United States
• PMID: 23557244 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoglobulin Fc Fragments
• Recombinant Fusion Proteins
• Receptor, EphA4

Topics

• Animals
• Blotting, Western
• Brain (drug effects, pathology)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Immunoglobulin Fc Fragments (pharmacology)
• Magnetic Resonance Imaging
• Rats
• Rats, Wistar
• Receptor, EphA4 (antagonists & inhibitors)
• Recombinant Fusion Proteins (pharmacology)
• Recovery of Function (drug effects)
• Spinal Cord Injuries (drug therapy, pathology)
• Transfection