Comparative and correlative neuroanatomy for the toxicologic pathologist

Xenobiotic-induced neuroanatomic alterations are always regarded as adverse and are commonly used to define reference doses to manage neurotoxic risk. Thus, the neuropathologist plays an essential role in evaluating potential neurotoxicants. The pathologist must be able to recognize the morphologic differences that exist among species, strains, and ages or between genders (comparative neuroanatomy) and to grasp the impact of structural damage on neural function (corrective neuroanatomy). Brain anatomy and function may b e used to group the mammals used in neurotoxicity bioassays into 3 classes: rodent, carnivore. and primate. Neural function may or may not be affected by the structural divergence. Rodents are preferred for neurotoxicity assa ys because their reduced body size allows optimal perfusion at little cost and their smaller brain size permits screening of multiple regions using fe w sections. However, care must be exercised when interpreting rodent neurop athology data because the rodent paleocortex does not recapitulate the soph isticated neocortical circuitry and functions of carnivores and primates. K nowledge of the neuroanatomic variations that exist among test species assi sts the neuropathologist in defining the relevance of structural alteration s, the potential clinical sequelae of such findings, and the possible signi ficance of similar changes in humans.