title: The delayed post-injury administration of soluble fas receptor attenuates post-traumatic neural degeneration and enhances functional recovery after traumatic cervical spinal cord injury.
abstract: Spinal cord injury (SCI) is a devastating condition that currently lacks clinically-relevant and effective neuroprotective therapeutic options. Optimal therapeutic agents for clinical translation should show efficacy in a cervical compression/contusion model using a clinically-relevant post-injury therapeutic time window. To date, few compounds have met that rigorous standard. The objective of this work was to evaluate the efficacy of delayed post-injury administration of soluble Fas receptor (sFasR) via intrathecal catheter following acute cervical SCI in a clinically-relevant contusion/compression model. Female Wistar rats were given a C7-T1 moderately severe clip compression injury, followed by either 8-h or 24-h delayed treatment initiation. Long-term neurobehavioral analysis of motor recovery and neuropathic pain development was undertaken. The extent of oligodendrocyte and neuron survival was assessed in peri-lesional cord sections 8 weeks post-SCI. This was complemented by an evaluation of the level of tissue preservation at and adjacent to the site of injury. In animals treated with sFasR delayed 8 h post-injury, significant behavioral effects were observed, coinciding with enhanced cell survival, peri-lesional tissue sparing, and enhanced integrity of descending fiber tracts compared to control treatments. Animals treated with sFasR delayed by 24 h showed more modest improvements in behavioral recovery, and had consistent improvements in cell survival and tissue preservation. This work has shown for the first time that the Fas-mediated apoptotic pathway can be therapeutically targeted in a clinically-relevant time window post-SCI.
authors.affiliation: Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sherri
authors.initials: S
authors.lastname: Robins-Steele
authors.forename: Dung Hoang
authors.initials: DH
authors.lastname: Nguyen
authors.forename: Michael G
authors.initials: MG
authors.lastname: Fehlings
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects; D005260:Female; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D013997:Time Factors; D019014:fas Receptor / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D019014:fas Receptor