Summary

Understanding glial cell responses under pathological conditions provides important information about marker proteins used to identify neurotoxic endpoints. Detection of changes in the expression of marker proteins based on immunohistochemical methods has inherent limitations and requires postmortem tissue. Validation of the PBR as a biomarker of neurotoxicity surmounts these limitations. The PBR is a glial protein that has been proven to be sensitive and specific in detecting sites of inflammation and brain damage. Studies from our laboratory and those of others support continued investigations on the use of the PBR as a biomarker of neurotoxicity. Considerable data has been generated in the validation of the PBR method in detecting chemical-induced neurotoxicity in rodent models. Ongoing studies are validating this methodology in nonhuman primates for subsequent studies in humans that are potentially exposed to environmental chemicals in the occupational setting. The ability to label the PBR-specific ligand PK11195 with positron-emitting radioisotopes makes possible the use of noninvasive PET scanning to study the PBR in the living human brain. The development of dedicated high-resolution PET scanners for studies in small animals such as rodents and small nonhuman primates will greatly facilitate the application of the PBR as an in vivo molecular biomarker of neurotoxicity.

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