Toxicologic Pathology Analysis for Translational Neuroscience

Abstract

A half-day American College of Toxicology continuing education course presented key issues often confronted by translational neuroscientists when predicting human risk from animal-derived toxicologic pathology data. Two talks correlated discrete structures with major functions in brains of rodents and nonrodents. The third lecture provided practical advice to obtain highly homologous rodent brain sections for quantitative morphometry in developmental neurotoxicity testing. The last presentation discussed demographic influences (eg, species, strain, sex, age), physiological attributes (eg, body composition, brain vascularity, pharmacokinetic/pharmacodynamic patterns, etc), and husbandry parameters (eg, group housing) recognized to impact the actions of neuroactive chemicals. Speakers described common cases of real-world challenges to animal data interpretation encountered when designing studies or extrapolating biological responses across species. The efficiency of translational neuroscience efforts will likely be enhanced as new methods (eg, high-resolution non-invasive imaging) improve our capability to cross-connect subtle anatomic and/or biochemical lesions with functional changes over time.

Comparative Pathology of the Peripheral Nervous System

“…Unlike CNS diseases, where neuropathological sequelae are impacted to some degree by neuroanatomical, neurobehavioral, and neurochemical divergence among species and strains, across sexes, and at different ages, 14,217 the PNS exhibits a relatively consistent anatomical organization and functional capacity in all vertebrates. The PNS is composed of ganglia (collections of neurons) and nerves that present information from peripheral receptors to the CNS.…”