TABLE 3.
Examples of potential neurotoxicity biomarkers used in longitudinal studies
| Fluid Based - Longitudinal and Minimally Invasive Direct Analysis of Plasma, Serum, Urine, or CSF | ||
|---|---|---|
| Biomarker | Endpoint | Comments |
| F2-IsoPs (F2-iso prostanes) | Indirect measurement of oxidative injury | Used clinically as biomarker of exposure |
| Not specific for neurotoxicity | ||
| Glial fibrillary acidic protein (GFAP) | Biomarker of all types of neural (neuronal and glial) damage | ELISA already developed |
| GFAP is a sensitive and specific marker of astrogliosis (indicative of all types of CNS damage) | ||
| Microtubule-associated protein (MAP-2) | Biomarker of dendritic injury | ELISA already developed |
| Myelin basic protein (MBP) | Biomarker of myelin disruption | Immunoassay developed but not widely used |
| Microtubule-associated protein tau (total τ, phosphorylated τ, and cleaved τ) | Biomarker of neurodegeneration/axonal injury | ELISAs developed |
| Neurofilament (light chain and phosphorylated heavy chain) | Biomarkers of axonal injury | ELISA exists |
| Spectrin breakdown product (SBDP-145) | Found in the CSF as a biomarker for neurodegeneration (apoptosis and necrosis) | Recently reported |
| TSPO (translocator protein) | Biomarker of activated glia | Has been validated in a variety of preclinical models of neurotoxicity including preclinical and clinical imaging |
| UCH-L1 (ubiquitin C-terminal hydrolase) | Biomarker of cell body injury | Immunoassay developed |
| Imaging - Less Invasive Longitudinal Analysis in Living Animals or High-Resolution in Post Mortem Fixed Animals | ||
| MRI T2 relaxation | Detects edema, hemorrhage, water redistribution, cellular disruption, cellular density, infiltration, blood flow changes, and temperature changes | Data obtained using T2 relaxation is quantitative Correlation to pathology can be achieved via digital analysis |
| Electroencephalography and in vivo electrophysiology | Permits repeated measurements of neural activity and dose-response effects within subject | Invasive Electrical, electrode, muscle, and movement artifact |
| Magnetic resonance spectroscopy (MRS) | Noninvasive Permits within-subject repeated measurements of brain metabolites associated with toxicity |
|
| Positron emission tomography (PET) | Minimally invasive in vivo imaging | |
| MicroPET | Molecular-level view of biochemical, physiologic, pathologic, and pharmacological processes in vivo | Tags for specific neurotransmitter receptor systems can be used Resolution less specific than MRI needs specific short-lived radiolabeled ligand to probe the function of interest |
CFS, cerebrospinal fluid; CNS, central nervous system.