Studying axonal degeneration and regeneration using in vitro and in vivo models: The translational potential

Since the initial studies by Cajal, multiple models of peripheral nerve degeneration and regeneration have been developed to address the ever-increasing complexity of the mechanisms involved in regeneration. In vitro models offer the principal benefit of a system that can be readily manipulated to address specific mechanistic questions in a deconstructed system. However, in vitro models can be overly simplified and intricacies of the interactions between neurons and glia can be lost. In vivo animal models seek to remedy some of these shortcomings, but most in vivo animal systems fail to precisely model human nerve regeneration. Rodent models of chronic nerve regeneration have been developed to better recapitulate human nerve regeneration, but are not widely used. An important development in the field has been the establishment of experimental nerve regeneration in humans, involving the reinnervation of the epidermis after cutaneous axotomy or topical capsaicin application. Use of such human models will likely accelerate the development and evaluation of new drugs that enhance peripheral nerve regeneration.