Functional evaluation of peripheral nerve regeneration and target reinnervation in animal models: a critical overview

Abstract

Peripheral nerve injuries usually lead to severe loss of motor, sensory and autonomic functions in the patients. Due to the complex requirements for adequate axonal regeneration, functional recovery is often poorly achieved. Experimental models are useful to investigate the mechanisms related to axonal regeneration and tissue reinnervation, and to test new therapeutic strategies to improve functional recovery. Therefore, objective and reliable evaluation methods should be applied for the assessment of regeneration and function restitution after nerve injury in animal models. This review gives an overview of the most useful methods to assess nerve regeneration, target reinnervation and recovery of complex sensory and motor functions, their values and limitations. The selection of methods has to be adequate to the main objective of the research study, either enhancement of axonal regeneration, improving regeneration and reinnervation of target organs by different types of nerve fibres, or increasing recovery of complex sensory and motor functions. It is generally recommended to use more than one functional method for each purpose, and also to perform morphological studies of the injured nerve and the reinnervated targets.

Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo

“…Hence, the increase of MF in the NGF groups would be in accordance with other studies that describe an important role of NGF on axonal sprouting (Diamond et al, 1987;Gloster et al, 1992;Ruiz et al, 2004). Thus, histological quantification of MFs may result in an overestimation of the number of regenerated neurons (Navarro 2015) and only the retrotracer study provides reliable information on the number of regenerating neurons. For these reasons, in our study the positive effects of the NTFs loaded MPs were indicated by the effective growth of axons that were able to capture the retrotracer placed distal to the nerve conduit.…”

AlphaB-crystallin regulates remyelination after peripheral nerve injury

“…These results indicate that overall functional recovery was impaired in the injured αBC −/− animals. Reduction in paw area, braking duration, and propulsion duration is suggestive of sensory and motor impairment (28). We, therefore, validated the DigiGait findings using classical motor (rotarod and walking track) and sensory (Hargreaves, Dynamic Plantar, and von Frey Hair) behavioral tests.…”

Reflex‐based grasping, skilled forelimb reaching, and electrodiagnostic evaluation for comprehensive analysis of functional recovery—The 7‐mm rat median nerve gap repair model revisited

“…To study novel approaches in peripheral nerve reconstruction and nerve graft tissue engineering, the sciatic nerve (SN) is easily accessible and its length provides the opportunity of addressing long gap repair (Tos et al., 2009) with a number of functional tests (Navarro, 2016). The SN model, however, is often inflicted by automutilation behavior and the development of hamstring contractions, eventually reducing the number of animals available for analysis and the significance of the results (Navarro, 2016; Weber, Proctor, Warner, & Verheyden, 1993).…”

“…The SN model, however, is often inflicted by automutilation behavior and the development of hamstring contractions, eventually reducing the number of animals available for analysis and the significance of the results (Navarro, 2016; Weber, Proctor, Warner, & Verheyden, 1993). …”