Continuing education course #3: current practices and future trends in neuropathology assessment for developmental neurotoxicity testing.

Published

Journal Article

The continuing education course on Developmental Neurotoxicity Testing (DNT) was designed to communicate current practices for DNT neuropathology, describe promising innovations in quantitative analysis and noninvasive imaging, and facilitate a discussion among experienced neuropathologists and regulatory scientists regarding suitable DNT practices. Conventional DNT neuropathology endpoints are qualitative histopathology and morphometric endpoints of particularly vulnerable sites (e.g., cerebral, cerebellar, or hippocampal thickness). Novel imaging and stereology measurements hold promise for automated analysis of factors that cannot be effectively examined in routinely processed specimens (e.g., cell numbers, fiber tract integrity). The panel recommended that dedicated DNT neuropathology data sets be acquired on a minimum of 8 sections (for qualitative assessment) or 3 sections (for quantitative linear and stereological analyses) using a small battery of stains to examine neurons and myelin. Where guidelines permit discretion, immersion fixation is acceptable for younger animals (postnatal day 22 or earlier), and peripheral nerves may be embedded in paraffin. Frequent concerns regarding DNT data sets include false-negative outcomes due to processing difficulties (e.g., lack of concordance among sections from different animals) and insensitive analytical endpoints (e.g., qualitative evaluation) as well as false-positive results arising from overinterpretation or misreading by inexperienced pathologists.

Full Text

Duke Authors

Cited Authors

  • Bolon, B; Garman, RH; Gundersen, HJG; Allan Johnson, G; Kaufmann, W; Krinke, G; Little, PB; Makris, SL; Mellon, RD; Sulik, KK; Jensen, K

Published Date

  • January 2011

Published In

Volume / Issue

  • 39 / 1

Start / End Page

  • 289 - 293

PubMed ID

  • 21075916

Pubmed Central ID

  • 21075916

Electronic International Standard Serial Number (EISSN)

  • 1533-1601

Digital Object Identifier (DOI)

  • 10.1177/0192623310386247

Language

  • eng

Conference Location

  • United States