Anti-inflammatory treatment confirms rsfMRI and TSPO PET as biomarkers of functional connectivity and neuroinflammation in rat contusion spinal cord injuries.

Abstract

A cascade of biological responses to spinal cord injury (SCI), including neuroinflammation, plays a pivotal role in determining long-term outcomes and has become a primary therapeutic target. Riluzole, a neuroprotective agent, has demonstrated efficacy in preserving tissue integrity and improving motor function following SCI. The study aims to use this established treatment to verify that resting-state fMRI (rsfMRI) functional connectivity (rsFC) and TSPO PET metrics are reliable biomarkers of SCI severity, progression, and treatment response. 16 male rats with a moderate lumbar contusion injury were administered Riluzole or HBC vehicle. rsfMRI and TSPO PET scans were collected post-SCI alongside motor-sensory behavioral tests. After SCI, significantly stronger rsFC between dorsal-to-dorsal gray matter horns rostral to the SCI was observed in the riluzole group, compared to the vehicle group. A majority of horn pairs rostral and caudal to injury exhibited significant decrease in rsFC over time for both groups and correlated with post-injury behavioral deficits and recovery. TSPO-PET detected increased SCI neuroinflammatory activity. Our results demonstrate reductions in rsFC disruption, validating the role of rsFC as biomarkers of SCI severity and progression. The imaging biomarkers can be used to evaluate the responsiveness to treatment and efficacy of novel therapies in preclinical studies.