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

作者:Spanevello Mark Damien; Tajouri Sophie Ines; Mirciov Cornel; Kurniawan Nyoman; Pearse Martin John; Fabri Louis Jerry; Owczarek Catherine Mary; Hardy Matthew Philip; Bradford Rebecca Anne; Ramunno Melanie Louise; Turnley Ann Maree; Ruitenberg Marc Jan; Boyd Andrew Wallace*; Bartlett Perry Francis
来源:Journal of Neurotrauma, 2013, 30(12): 1023-1034.
DOI:10.1089/neu.2012.2729

摘要

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.

全文