The delayed post-injury administration of soluble fas receptor attenuates post-traumatic neural degeneration and enhances functional recovery after traumatic cervical spinal cord injury.
J Neurotrauma
; 29(8): 1586-99, 2012 May 20.
Article
en En
| MEDLINE
| ID: mdl-22260324
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Traumatismos de la Médula Espinal
/
Receptor fas
/
Recuperación de la Función
/
Degeneración Nerviosa
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
J Neurotrauma
Asunto de la revista:
NEUROLOGIA
/
TRAUMATOLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Canadá