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.
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The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
The authors gratefully acknowledge Zou Yue and Chaohui Tang for their assistance with surgical procedures and perfusion of animals, the Center for Small Animal Imaging (CSAI) staff for imaging support, and the Vanderbilt University Medical Center (VUMC) Translational Pathology Shared Resource Core (NCI/NIH Cancer Center Support Grant 2P30 CA068485-14) for their expertise with processing the spinal cord tissue histology.
Funding
This study is supported by DOD Grant SC190134 (awarded to LMC), NIH Grant F31 NS113949 (awarded to CM), and acknowledges the support also of NIH award 1S10OD025085 (awarded to JCG). We acknowledge additional NIH support for instrumentation grants 1S10OD016245-01 and 1S10RR023784-01.
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All authors contributed extensively to the work. CM, LMC, and JCG designed the experimental studies and procedures. XY and ML designed and tested the MRI coil hardware used in the study. CM and JLR performed surgical procedures, animal care, and collected behavior data. CM and FW collected MR data and optimized MR sequences. MNT collected and processed PET imaging data, with the assistance of CM. CM, JLR, and LMC performed perfusion and spinal cord tissue extraction. CM analyzed the MRI and behavioral data with the assistance of FW. and J.L.R. CM and JLR performed histology image quantification. CM drafted the manuscript and prepared the figures. All authors provided feedback and revisions for the manuscript. All authors reviewed and approved the final version of the manuscript.
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Mu, C., Reed, J.L., Wang, F. et al. Anti-inflammatory treatment confirms rsfMRI and TSPO PET as biomarkers of functional connectivity and neuroinflammation in rat contusion spinal cord injuries. Sci Rep (2026). https://doi.org/10.1038/s41598-026-42844-x
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DOI: https://doi.org/10.1038/s41598-026-42844-x
