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.

Comparison of Renal Artery, Soft Tissue, and Nerve Damage After Irrigated Versus Nonirrigated Radiofrequency Ablation

“…. 17 Digestion chambers were characterized by the presence of aggregated myeline (eosinophilic hyaline globules) and vacuolization at the periphery of the cell with or without vesicular nuclei interspersed.…”

A Histopathological Study of Bovine Ganglia

“…Renaut bodies in peripheral nerves primarily consist of fibroblasts that are thought to proliferate as a physiological reaction to mechanical stresses (Elcock et al, 2001). While Renaut bodies have been reported mainly at sites of nerve compression in man and horses (Duncan et al, 1987;Piña-Oviedo et al, 2009), these constituted common incidental findings in healthy dogs (Whitney et al, 2011). Previously unreported in cattle, the Renaut bodies found in the present study were deemed incidental findings as no pathological significance or relationship to age was found.…”

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

“…2,9 Supporting the idea of a link with mechanical stress, these structures have been found in the peripheral nerves of a range of species over the years, including man, elephant, dog, hamster, rat, and cattle. 4,5,7,[10][11][12][13][14] The nerves in which they were found were usually located in anatomical areas naturally susceptible to such stress and injury, for instance, the peripheral nerves of the elephant's trunk, which is used as a prehensile organ 11 or classically at the site of entrapment of median and ulnar nerves in man. 5,10 Furthermore, as in the currently acknowledged hypothesis, RBs could be successfully induced in animals undergoing mechanical stress, such as repeated mechanical trauma or compression.…”

“…13 In addition, they also appear to be frequent incidental findings in experimental control Beagle dogs used in toxicity studies and were even described as part of the spontaneous background changes in a review of these dogs’ spontaneous microscopic changes in the sciatic nerve. 12,17…”