title: Neuropathology standards: what constitutes an optimal histomorphologic evaluation of the nervous system in general toxicity studies.
abstract: The identification of neurotoxicity is a critical issue in drug development, and toxicologic pathologists play an important role in this effort. Neuropathology is a specialized area of toxicologic pathology in which a substantial number of nonroutine techniques and methods have been developed, and there are undoubtedly many instances in which these specialized procedures have helped characterize a neuropathologic lesion. Routine histopathologic methods employed in general toxicologic pathology studies are needed to identify the complete range of possible neuropathologic changes; once identified, many of these changes can be better defined by specialized techniques, such as immunohistochemistry, to confirm cell types involved. Sometimes, when neurotoxicity is expected, dedicated studies can be designed a priori and optimized for detection of the anticipated effects. However, when neurotoxicity arises unexpectedly or there is uncertainty around the potential for neurotoxicity, the decision of what to do can become more difficult. Recommendations to go ahead and perform the "optimal" study design that would accommodate all the potentially useful specialized techniques for characterizing a neuropathologic change are sometimes not practical and can be unnecessary and potentially detrimental to other end points in the study. In addition, there is not always agreement on when specialized techniques would be required and which ones should be used when necessary. Two techniques in particular that are commonly recommended to help facilitate the detection of neuropathologic lesions are perfusion fixation and the Fluoro-Jade stain.
authors.affiliation: Pfizer, Inc, Groton, Connecticut 06340, USA. christopher.houle@pfizer.com
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Houle
mesh_terms: D000818:Animals; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D005452:Fluoresceins; D006652:Histological Techniques / Q000379:methods / Q000592:standards; D007150:Immunohistochemistry; D009420:Nervous System / Q000033:anatomy & histology* / Q000473:pathology*; D009488:Neurosciences / Q000379:methods* / Q000592:standards*; D020258:Neurotoxicity Syndromes / Q000473:pathology*; D009930:Organic Chemicals / Q000378:metabolism; D010477:Perfusion / Q000379:methods; D012107:Research Design; D018570:Risk Assessment; D014116:Toxicology / Q000379:methods / Q000592:standards
chemical_list: D005452:Fluoresceins; D009930:Organic Chemicals; C435731:fluoro jade