Atlas of Normal Microanatomy, Procedural and Processing Artifacts, Common Background Findings, and Neurotoxic Lesions in the Peripheral Nervous System of Laboratory Animals

Abstract

The ability to differentiate among normal structures, procedural and processing artifacts, spontaneous background changes, and test article–related effects in the peripheral nervous system (PNS) is essential for interpreting microscopic features of ganglia and nerves evaluated in animal species commonly used in toxicity studies evaluating regulated products and chemicals. This atlas provides images of findings that may be encountered in ganglia and nerves of animal species commonly used in product discovery and development. Most atlas images are of tissues from control animals that were processed using routine methods (ie, immersion fixation in neutral-buffered 10% formalin, embedding in paraffin, sectioning at 5 µm, and staining with hematoxylin and eosin) since these preparations are traditionally applied to study materials produced during most animal toxicity studies. A few images are of tissues processed using special procedures (ie, immersion or perfusion fixation using methanol-free 4% formaldehyde, postfixation in glutaraldehyde and osmium, embedding in hard plastic resin, sectioning at 1 µm, and staining with toluidine blue), since these preparations promote better stabilization of lipids and thus optimal resolution of myelin sheaths. Together, this compilation provides a useful resource for discriminating among normal structures, procedure- and processing-related artifacts, incidental background changes, and treatment-induced findings that may be seen in PNS tissues of laboratory animals.

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Nonproliferative and Proliferative Lesions of the Dog

“…Subperineurial accumulations of elongate, loosely whorled, mucin-rich, cell-poor connective tissue that occur in various peripheral nerves, especially in the distal branches of the sciatic nerve branches tibial and fibular nerve, and less commonly in autonomic nerves near viscera. 117…”

Proliferative and Nonproliferative Lesions of the Rat and Mouse Central and Peripheral Nervous Systems: New and Revised INHAND Terms

“…Occasionally, neuronal autophagy may be difficult to distinguish from "dystrophy, axonal" (or spheroids), a potentially reversible indication of disrupted axonal transport, 4 or normal axon hillocks (ie, the enlarged proximal portion of the axon where it arises from the neuron cell body). The morphologic similarity between this neuronal change and these 2 axonal morphologies reflects a plane-of-section artifact where a neuron undergoing autophagy is cut tangentially through a peripheral portion of the cell body.…”

“…The Schwann cell proliferation is a response to cyclic demyelination and regeneration of myelin and can cause thickening of nerves (hypertrophic neuropathy). 4…”

“…Onion bulbs are found most commonly in nerves showing the greatest evidence of segmental demyelination. The Schwann cell proliferation is a response to cyclic demyelination and regeneration of myelin and can cause thickening of nerves (hypertrophic neuropathy) 4.…”

Unusual Incidence and Location of Renaut Bodies in Beagle Dogs in a Nonclinical Study

“…To the best of our knowledge, this is the first time RBs around adrenal glands are reported in the literature. However, one of the authors (E.B.-T.) has observed isolated cases in former toxicity studies that he did not document systematically at the time, and they have recently been reported as sometimes occurring in the autonomic nerves of dogs by Pardo et al 3…”