Therapeutic strategies for peripheral nerve injuries: FK506 and electrostimulation

Abstract

Efficacious therapeutics for peripheral nerve injuries remain incompletely described in the literature. However, over the last several decades, delivery of FK506 (Tacrolimus) and electrostimulation have demonstrated great promise for supplementing surgical advances in treating peripheral nerve injuries. This review describes the discovery, mechanistic investigations, and clinical translation of these strategies to promote functional recovery. FK506 has demonstrated the ability to increase the regeneration rate after nerve injury by a variety of hypothesized mechanisms, yet clinical utility remains limited due to systemic immunosuppression. Local administration of FK506 continues to be an active area of inquiry for minimizing side effects while maintaining its neuroregenerative effects. Electrostimulation of a nerve proximal to the site of surgical nerve repair has demonstrated increased axonal regeneration and accelerated recovery of both motor and sensory nerves. In addition, electrostimulation also appears to improve axon matching during reinnervation from motor to motor and sensory to sensory pathways and is used clinically in our surgeries. However, the specific parameters to best incorporate electrostimulation into the operating theater are still evolving. Utilizing translational rodent and murine models, surgical techniques and these therapeutic strategies have gradually become more viable as safety profiles and mechanisms are gradually understood. This review presents the state of the field for these therapeutic avenues and discusses further areas of research.