Student Competition (Knowledge Generation) ID 1987946

Abstract

NX210c is a 12-amino acid peptide derived from conserved thrombospondin type 1 repeat sequences in the subcommissural organ-spondin, which has a unique multifunctional mechanism of action to ameliorate outcomes following neurological injuries. The aim of this study was to evaluate the efficacy of NX210c to promote functional recovery and tissue repair in a cervical traumatic spinal cord injury (SCI) model. Adult female Wistar rats were subjected to a C6/C7 clip compression-contusion injury and treated once daily with intraperitoneal injections of NX210c (8 mg/kg) or its vehicle for 8 weeks, beginning 4 hours (h) or 8h post-injury (n=16-17/group), with concurrent neurobehavioural tests. Earlier NX210c administration at 4h increased forelimb grip strength (p<0.05) and improved several static and dynamic aspects of locomotion including regularity index and base of support of the forelimbs (CatWalk) (p<0.05). Delaying initial administration of NX210c to 8h, promoted weight gain, accelerated bladder control recovery from 14 to 9 days post-injury, and improved trunk balance (inclined plane) as early as one-week post-injury (p<0.05). 94% of NX210c-treated rats compared to 75% of vehicle controls observed weight support at the delayed initial injection timepoint. Histology (n=6/group) demonstrated greater white matter preservation and reduced cavity size at the injury epicenter, and higher neuronal soma counts caudally, with NX210c starting 8h post-injury compared to the vehicle (p<0.05). NX210c targets various aspects of SCI, improving motor function, bladder control, white matter preservation, and neuronal counts, with more benefits observed at the later initial injection timepoint.