Neuropathological Analysis of the Peripheral Nervous System

STP Position Paper: Recommended Best Practices for Sampling, Processing, and Analysis of the Peripheral Nervous System (Nerves and Somatic and Autonomic Ganglia) during Nonclinical Toxicity Studies

“…Typically, distal nerve branches are preferred for evaluation since they usually contain a high proportion of sensory axons, and clinical cases of peripheral neuropathy often present as altered sensation (Martyn and Hughes 1997;Azhary et al 2010). Furthermore, hind limb nerves rather than forelimb nerves usually are sampled in toxicity testing because the longer nerve fibers that serve the hind limb usually are affected first during peripheral neuropathies (Krinke 2011). That said, forelimb nerve branches also should be harvested if the in-life neurological signs suggest that forelimb function has been affected.…”

“…Weights typically are acquired from isolated biceps brachii, biceps femoris, gastrocnemius, and/or quadriceps femoris, which can be easily identified and collected in a consistent fashion (Greene 1935;Vleggeert-Lankamp 2007;Magette 2012). When a muscle weight will be included as an end point, the working group recommends the gastrocnemius for weighing since peripheral neuropathies usually occur first in portions of longer axons (which in the hind limb are most distant from their supporting neuronal cell bodies; Krinke 2011). Care is required in interpreting the relevance of muscle weights as meaningful conclusions may be impossible in situations where animals were in moribund condition or impacted by other toxicities (e.g., if weights were gathered from samples taken near the site of local test article administration or from long-term recumbent animals) or where historical control data are limited or nonexistent.…”

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

“…Where possible, the use of the appropriate second-tier term "degeneration, axonal" and "demyelination" is recommended, rather than "degeneration, nerve fiber," for lesions in which the pathogenesis has been confirmed using neurohistological stains (eg, silver impregnation [Bielschowsky's, Bodian's] or IHC to detect cell typespecific cytoskeletal elements such as anti-NFP or anti-MBP) or other diagnostic methods (eg, electron microscopy, teased nerve fiber preparations) to unambiguously identify the structure (ie, axon or myelin sheath) that is the primary target of injury. 7,12 Nerve fiber degeneration as a spontaneous aging change in nerve roots of rodents sometimes has been termed "radiculoneuropathy" historically for chronic toxicity (26 weeks) and carcinogenicity studies (see below for the new INHAND definition of this historical term). However, in general for pathology reports the more precise descriptive term ("degeneration, nerve fiber") accompanied by a comment that spinal nerve roots are the affected site should be used as the diagnosis in the data tables while radiculoneuropathy should be employed only as a summary interpretive term (like chronic progressive nephropathy [CPN]) in the narrative.…”

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

“…1 They have been described in humans at sites of chronic nerve entrapment 2,3 as well as in control beagle dogs 4,5 and horses. 4,6,7 Indeed, the incidence of RB in dogs may be quite high (36% and 46% for subchronic and chronic studies, respectively 5 ). Renaut bodies have been reported as an ancillary finding in hypertrophic neuropathy.…”