Case Report: Canine Strain– and Study Condition–Dependent Formation of Renaut Bodies in Sciatic Nerves of Beagle Dogs

Abstract

Two beagle dog strains were used in a 14-day intrathecal infusion study for a small molecule test article. A moderate number of Renaut bodies (RBs) were observed in the sciatic nerves of control and test article–treated adult animals as early as 1 day after test article infusion (ie, 5 days after catheter implantation in the lumbar cistern). In most cases, the sciatic nerve was affected unilaterally, apparently in association with extended lateral recumbency on one side. The lighter beagle strain (Marshall), and especially the females (which weighed less than age-matched Marshall males), developed more RBs. In contrast, neither females nor males of the larger strain (Harlan) developed any nerve lesions. These data support the hypothesis that RBs develop following mechanical stress to sciatic nerves, suggest that this change may develop fairly quickly following an insult, and demonstrate that different dog strains exhibit strain-specific nerve changes.

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

“…Renaut bodies may be formed in areas of nerve compression and can affect a large proportion of animals (including multiple controls) in some toxicity studies. 65,66 Finally, isolated neurons or small neuron clusters may be observed in many nerves in proximity to ganglia (Figures 12 and 55). These cells may represent either ectopic ganglionic neurons (Figure 55) or autonomic neurons ( Figure 12).…”

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

“…13 Regarding RBs in the sciatic nerve, Weber et al also suggest that the incidence of RBs could be linked to weight, the nerves of lighter subjects examined (Marshall Beagle dogs) not being as well-protected by overlying fat and muscle tissue as the ones of heavier individuals (Harlan Beagle dogs). 9 The incidence of RBs in the sciatic nerve in the current study could thus possibly be linked to the use of this light-weighted strain of Beagle dog. However, the dogs gained significant weight over time, and the sciatic nerves of heavier subjects were affected as much as the lighter (Table 2).…”

“…[6][7][8] Although their function is still debated, they have mainly been thought to be secondary to mechanical injury, and Renaut initially believed they could act as cushions that would protect long nerves in anatomical regions susceptible to such damage. 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.…”

“…First, the incidence in the sciatic nerve exceeds what we are used to encountering in toxicity studies performed for Janssen R&D. However, Weber et al recently reported an incidence of RBs in 3 of 4 females and 6 of 7 males in Marshall Beagle dogs from French origin. 9 Our second reason is to highlight the presence and significant number of RBs in autonomic nerves around the adrenal glands, an anatomical location that is neither subject to nerve entrapment nor likely to undergo significant mechanical stress. As a short reminder, the autonomic innervation of the adrenal gland is divided into extrinsic innervation (mostly cholinergic preganglionic sympathetic fibers) and intrinsic innervation (ganglion cells scattered throughout the organ).…”

Special Issue on Toxicologic Neuropathology of the Peripheral Nervous System: A Special Compendium of Past, Present, and Future Developments in a Neglected Field

“…Kaliyaperumal et al 70 review the biology of pain, available rodent pain models, and discussed the important role of pathologists in interpreting data and validating these models. This section concludes with a series of case reports exploring common iatrogenic PNS lesions associated with experimental manipulation rather than test article administration ( Bangari et al ); 71 unusual manifestations of autonomic neuropathy ( Walters et al ), 72 which historically is a vastly unappreciated aspect of PNS neurotoxicity; and common PNS background findings ( Butt et al 73 and Weber et al 74 ) that should not be assigned as test article-related lesions.…”