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Circulating Biomarkers of Neurotoxicity: Identifying fluidic endpoints correlating with central nervous system toxicity in a rodent model of neurotoxicity
Citation:
Imam, S., Z. He, S. Lantz, J. Raymick, B. Robinson, E. Cuevas, S. Sarkar, C. Law, J. Hanig, D. Herr, D. Macmillan, A. Smith, S. Liachenko, J. O'Callaghan, D. Miller, C. Somps, I. Pardo, J. Pierson, R. Roberts, B. Gong, W. Tong, M. Aschner, M. Kallman, D. Calligaro, S. Ferguson, M. Paule, AND W. Slikker. Circulating Biomarkers of Neurotoxicity: Identifying fluidic endpoints correlating with central nervous system toxicity in a rodent model of neurotoxicity. Society of Toxicology Annual Meeting, Baltimore, MD, March 10 - 14, 2019.
Impact/Purpose:
This effort by a consortium of government, NGO, academia, and industry scientists will present a comprehensive correlation of TMT-induced neuropathology with several observed biomarkers an MRI-based endpoints, suggesting specific pathways involved in neurotoxicity that can be assessed using peripheral fluids.
Description:
Neurotoxicity has been linked with exposure to a number of common drugs and chemicals, yet efficient, accurate, and minimally-invasive methods to detect it are lacking. Fluid-based biomarkers such as those found in serum, plasma, urine, and cerebrospinal fluid (CSF) have great potential due to the relative ease of sampling but at present, data on their expression and translation are lacking or inconsistent. Here, we present our observation on biomolecules that have some promise for identification of neurotoxicity that was induced by a single intraperitoneal injection of the known neurotoxic agent, trimethyltin (TMT). A single dose of TMT led to significant alterations in total oxidative stress markers, changes in lipid homeostasis, circulating interleukins and related factors, and markers of neuroinflammation, thus, providing opportunities to explore their correlation with the traditional neuropathology and magnetic resonance imaging (MRI) that defines neurotoxicity. Our data will present a comprehensive correlation of TMT-induced neuropathology with several observed biomarkers an MRI-based endpoints suggesting specific pathways that can be assessed using peripheral fluids.