Light Microscopic Sciatic Nerve Changes in Control Beagle Dogs from Toxicity Studies

Abstract

Although the dog is a common choice among nonrodent species in evaluation of compound safety for regulatory submission, information regarding the incidence of spontaneous or incidental microscopic changes in canine peripheral nerve is limited. A retrospective examination was performed of routine histologic preparations of sciatic nerve from eighty-one control dogs in toxicity studies ranging from ten days to three months in duration. Spontaneous background changes included digestion chambers, foci of vacuolation, nerve fibers circumscribed by proliferating Schwann cells (bands of Büngner), and small foci of myelin aggregation. The latter accounted for 91% of the microscopic changes and were noted in all sections examined. These changes were quantified, and the number per square millimeter of evaluable nerve tissue was determined for each slide. Densities of foci varied among the slides examined; no age- or sex-related trends were apparent. In addition, anatomic features of peripheral nerves including nodes of Ranvier, Schmidt-Lanterman incisures, Renaut bodies, and effects resulting from sectioning plane were noted. By demonstrating the range of effects observed within control animals, these observations provide a basis for recognition of possible compound-related effects in routine nerve preparations from dogs included in toxicity studies.