Evaluation Tools and Animal Models of Peripheral Neuropathies

Abstract

Peripheral neuropathies are common and frequently debilitating disorders linked to degeneration of peripheral nerves that supply mainly the distal muscles of the extremities. Due to the diverse origin of the pathology (genetic, systemic or environmental), peripheral neuropathies exhibit different clinical forms: acute or chronic, symmetrical or asymmetrical, demyelinating or axonal. In the last 30 years, to gain insight into cellular and molecular mechanisms underlying neuropathies, numerous animal models – either spontaneous or induced by chemical compounds, physical injury or genetic engineering – have been extensively developed and used. In this review, we present (1) the methods used to assess the peripheral neuropathies in the major available animal models and their main pathological characteristics and (2) the main models and their relevance to the human pathology, and, consequently, their usefulness for preclinical studies. Finally, we discuss the emerging, recently developed tools, that should allow to gain a better insight into the mechanisms underlying the peripheral neuropathies.

Chronic exposure to rotenone, a dopaminergic toxin, results in peripheral neuropathy associated with dopaminergic damage

“…Animal models of neuropathy mediated by chemical toxicants are broadly relevant to the area of neurotoxicology. Motor nerve conduction velocity (MCV) testing is frequently used in experimental models of neurotoxicity caused by exposure to aromatic compounds [8] and pesticides [5] or associated with metabolic disorders (e.g., diabetes) neuropathies [7]. In human electro-diagnostic medicine, the testing of motor axons allows one to reliably detect conduction block associated with multifocal demyelination [9].…”

Use of Nerve Conduction Assessments to Evaluate Drug-Induced Peripheral Neuropathy in Nonclinical Species—A Brief Review

“…There are several useful published reviews of the animal models used for peripheral neuropathy assessments, which are beyond the scope of the current review. 13,[16][17][18] Histopathological assessment of PNS morphology via nerve biopsy is the gold standard assessment to confirm diagnosis of peripheral neuropathy as it is highly validated and provides definitive evidence of injury and corresponding severity. However, histopathology is limited in some aspects, for example, there is only a narrow window of time where dead and dying cells can be captured microscopically, after which there is no evidence of axon organelles and potentially any evidence of the presence of axon may disappear.…”

Small Rho GTPases are key regulators of peripheral nerve biology in health and disease

“…The discovery of the central role of neuregulin signaling ( Nave and Salzer, 2006 ) as well as the elucidation of the molecular mechanisms involved in the determination of nodes of Ranvier and their neighboring structures serve as prominent examples ( Schafer and Rasband, 2006 ) . Furthermore, it has become obvious that altered interactions between glia cells and axons are a major part of the underlying disease mechanisms of various human neuropathies ( Suter and Scherer, 2003; Fricker et al, 2008 ) .…”