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Biomarkers of Chemical-induced Central Nervous System Damage
Citation:
Imam, S., Z. He, S. Rogstad, S. Burks, J. Raymick, B. Robinson, E. Cuevas, S. Sarkar, C. Law, J. Hanig, D. Herr, D. MacMillan, A. Smith, S. Liachenko, O. James, C. Somps, C. Tyszkiewicz, C. Liu, G. Teuns, K. Ruprecht, M. Kothe, C. Otto, J. Pierson, R. Roberts, B. Gong, W. Tong, M. Aschner, M. Kallman, M. Paule, AND W. Slikker. Biomarkers of Chemical-induced Central Nervous System Damage. Safety Pharmacology Society, N/A, Virtual Meeting, October 04 - 08, 2021.
Impact/Purpose:
Neurotoxicity has been linked to exposure to a number of common drugs and chemicals, yet efficient and minimally-invasive methods for prediction of neurological changes are lacking. Our data demonstrate novel correlations of several of these neurotoxicity biomarkers with TMT-induced neuropathology. These findings suggest involvement of specific pathways that can be assessed using peripheral fluids in a preclinical model.
Description:
Neurotoxicity has been linked to exposure to a number of common drugs and chemicals, yet efficient and minimally-invasive methods for prediction of neurological changes are lacking. Biological products such as those found in serum, plasma, urine, and cerebrospinal fluid (CSF) have great potential as biomarkers of neurotoxicity and are relatively easy to collect. However, data on their expression and clinical translation are lacking or inconsistent. As part of the HESI Neurotoxicity Biomarker Subcommittee and the IMI-2 TransBioLine Consortium, we present preclinical biomarker data from 2 trimethyltin (TMT) in vivo studies in rats. TMT causes a central nervous system (CNS) selective neuropathology in animal species and humans. A single dose of TMT (7 mg/kg, ip) caused typical neuropathology lesions in the hippocampus along with alterations in MRI measures, lipid homeostasis and markers of neuroinflammation and neurotoxicity in CSF, serum, plasma or urine. Our data demonstrate novel correlations of several of these neurotoxicity biomarkers with TMT-induced neuropathology. These findings suggest involvement of specific pathways that can be assessed using peripheral fluids in a preclinical model. Additionally, a validation of select fluidic biomarkers derived from this TMT approach will be discussed in animal models of rotenone- or cuprizone-induced neurotoxicity to obtain minimally invasive indicators of neuron- or myelin-specific damage.