A standardized in vivo platform for preclinical screening of therapeutic interventions in rat thoracic spinal cord injury.

Reproducibility remains a challenge in spinal cord injury (SCI) research, and the absence of standardized preclinical models and outcomes slows clinical translation of promising findings. Contract research organization CRO-based screening platforms partially address this in epilepsy and pain, yet no equivalent resource exists for SCI. Thus, the Christopher & Dana Reeve Foundation partnered with PsychoGenics, Inc. and an expert panel to develop a standardized, blinded screening platform using a rat mid-thoracic (T8) contusion model tested across four severities on Infinite Horizons impactor device (170, 200, 250, and 250 Kdyn+3 s dwell time; n = 15/group). Outcome measures included open field locomotion assessed by Basso Beattie Bresnahan locomotor rating scale and NeuroCube, an automated gait analysis system using computer vision and machine learning to quantify gait, as well as horizontal ladder, mechanical, heat and cold allodynia, and immunohistochemical assessment of the SCI. Most measures distinguished injury severities from Sham and several demonstrated graded effects across severity levels. BBB scores at 5 weeks mapped onto distinct locomotor milestones, while NeuroCube analysis captured compensatory adaptations, namely forward weight shift, wider base of support, and increased forelimb reliance. Hindlimb error rates on the horizontal ladder ranged from 22% to 95% and corresponded to SCI severity. Mechanical and cold allodynia occurred in all SCI groups, increasing with severity. Histologically, the spared tissue area and volume measurements are sensitive measures for distinguishing injury severity, correlating strongly with BBB, ladder, cold allodynia, and NeuroCube outcomes. This standardized platform reliably detects functional and histological differences across clinically relevant thoracic SCI severities. It offers a reproducible, objective resource for industry and academic investigators seeking to evaluate therapeutic candidates in the SCI discovery pipeline.