title: 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.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Mark Damien
authors.initials: MD
authors.lastname: Spanevello
authors.forename: Sophie Ines
authors.initials: SI
authors.lastname: Tajouri
authors.forename: Cornel
authors.initials: C
authors.lastname: Mirciov
authors.forename: Nyoman
authors.initials: N
authors.lastname: Kurniawan
authors.forename: Martin John
authors.initials: MJ
authors.lastname: Pearse
authors.forename: Louis Jerry
authors.initials: LJ
authors.lastname: Fabri
authors.forename: Catherine Mary
authors.initials: CM
authors.lastname: Owczarek
authors.forename: Matthew Philip
authors.initials: MP
authors.lastname: Hardy
authors.forename: Rebecca Anne
authors.initials: RA
authors.lastname: Bradford
authors.forename: Melanie Louise
authors.initials: ML
authors.lastname: Ramunno
authors.forename: Ann Maree
authors.initials: AM
authors.lastname: Turnley
authors.forename: Marc Jan
authors.initials: MJ
authors.lastname: Ruitenberg
authors.forename: Andrew Wallace
authors.initials: AW
authors.lastname: Boyd
authors.forename: Perry Francis
authors.initials: PF
authors.lastname: Bartlett
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D051381:Rats; D017208:Rats, Wistar; D036122:Receptor, EphA4 / Q000037:antagonists & inhibitors*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology; D014162:Transfection
chemical_list: D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; D036122:Receptor, EphA4
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