Abstract
P49
Introduction: The spinal cord is the major connection between the brain and peripheral nerves. Spinal cord injury (SCI) leads to significant and often permanent loss of sensory and motor functions, sometimes even death. The loss of sensory and motor function is directly related to the cascade of cellular and molecular events resulting from injury, including inflammation and demyelination {1, 2}. Both rodent SCI models and SCI patients demonstrate worsened functional outcome after injury, and research has suggested this is due to exacerbated pathophysiological changes after SCI in the aged population. This study aimed to assess demyelination and neuroinflammation in a rat model of SCI in both young and aged rats using non-invasive imaging to explore post-injury pathophysiology.
Methods: Young adult (4 months) and aged (12 month) male Sprague Dawley rats were used in this study. For SCI, the animals received a laminectomy around vertebral level T9, and moderate contusion injury (200 kdyne force) was induced with the Infinite Horizons Impactor (Precision Systems Incorporated, Natick, Maat). PET/CT images were acquired using Siemens Inveon preclinical scanner. The two radiotracers used for PET imaging were [18F] 3F4AP (fluoro-4-aminopyridine), a demyelination marker showing preferential binding in areas of low myelin content {3}, and [18F] DPA-714, a marker for increased expression of translocator protein (18-kDa, TSPO) for neuroinflammation {4}. The 3F4AP PET scans were acquired at baseline and 5 days post-injury. The DPA-714 PET scans were acquired at baseline and 6 days post injury. The tracer uptake was assessed by drawing a volume of interest (VOI) in the injured thoracic spinal cord, uninjured cervical spinal cord (C2-C5), and uninjured cerebellum (brain) region of the subjects, using Siemens Inveon Workplace software (V4.2) [Figure 1]. Standardized Uptake Value (SUV) for all three VOI's were plotted to compare the changes from baseline to post-injury time point in the two radiotracers. Alterations in the tracer SUV were also evaluated between the aged and young group of animals.
Results: Elevation in demyelination (3F4AP) and TSPO marker (DPA-714) tracers were detected in the injury site (thoracic) in the post-injury scans in both aged and young animals, when compared to its baseline scans [Figure 2 & 3]. No change in the tracer uptake was observed in the non-injured regions which were distal to the injury site (cerebellum and cervical spinal cord) [Figure 2 & 3]. Compared to the young animals, the aged animals showed increased tracer uptake at the injury site for both demyelination (3F4AP) and TSPO (DPA-714) markers [Figure 4].
Conclusions: Demyelination and neuroinflammation after SCI can be detected non-invasively using PET TSPO and demyelination tracers. These tracers have demonstrated sensitivity to injury and detected differences in pathology induced by elevated age at a sub-acute time point. PET/CT imaging using these tracers can be beneficial to monitor prognosis and therapeutic effects after SCI, and have now demonstrated exacerbated pathology after injury in the aged versus young population.
Acknowledgment: This work was supported by the Uniformed Services University Bridge Funding for Dr. Byrnes.
Disclaimer: The opinions or assertions contained herein are the private ones of the author/speaker and are not to be construed as official or reflecting the views of the Department of Defense or the Uniformed Services University of the Health Sciences.
Reference:
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• Hellenbrand DJ, et. al. J Neuroinflammation. 2021;18(1):284.
• Guehl NJ, et. al.. J Cereb Blood Flow Metab. 2021;41(7):1721-1733.
• Guilarte TR, et. al. Pharmacol Ther. 2022 Jun;234:108048.
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