Skip to main content
2024 ACTOX Main banner
Icon Legend
This session is not in your schedule.
This session is in your schedule. Click again to remove it.

    Poster

    T2-MRI Mapping and Fluidic Neurofilament Light (NfL) as a Minimally Invasive Correlate of Central Nervous System (CNS) Toxicity in a Cuprizone Model: A Biomarker Study (P121)

    Monday, November 18, 2024
    5:00 PM - 6:30 PM CT
    Neurotoxicity has been linked to exposure to a number of drugs and chemicals. However, efficient, predictive, and minimally-invasive methods to detect neuroanatomical effects are not routinely used in non-clinical assessments. We have shown significant T2-MRI changes in a rat model of trimethyltin neurotoxicity that correlates with CNS neurotoxicity and pathology as visualized by Flouro Jade C staining. Our primary objective was to identify possible T2-MRI relaxation changes that predict myelin specific neurotoxicity resulting from exposure to the known neurotoxic agent, cuprizone, and correlate T2-MRI relaxation with fluidic NfL and neuropathological endpoints. Adult-male rats (3-months old) were exposed to a daily dose of cuprizone (600 mg/kg p.o., daily) or corn oil for 4 weeks. Prior to treatment, animals underwent MRI scans to establish baseline. Additional MRI scans were performed weekly after beginning exposure to cuprizone. At the end of 4 weeks, a final MRI was completed, and animals were sacrificed for collection of fluids and tissue samples. Significant increase in T2-MRI relaxation was observed in the deep cerebellar nuclei (DCN) in cuprizone-treated rats compared to controls. CNS pathology of post-mortem brain also shows damage to the DCN, a possible correlation with MRI changes. Additionally, both plasma and serum NfL were significantly increased after exposure to cuprizone. Our data demonstrate that MRI-based endpoints and fluidic NfL levels may represent robust minimally invasive neurotoxicity biomarkers in a myelin-specific neurotoxicity model. Disclaimer. This presentation reflects the views of the authors and does not necessarily reflect those of the Food and Drug Administration.