Current perspectives on peripheral nerve repair and management of the nerve gap.

From the first surgical repair of a nerve in the 6th century, progress in the field of peripheral nerve surgery has marched on; at first slowly but today at great pace. Whether performing primary neurorrhaphy or managing multiple large nerve defects, the modern nerve surgeon has an extensive range of tools, techniques and choices available to them. Continuous innovation in surgical equipment and technique has enabled the maturation of autografting as a gold standard for reconstruction and welcomed the era of nerve transfer techniques all while bioengineers have continued to add to our armamentarium with implantable devices, such as conduits and acellular allografts. We provide the reader a concise and up-to-date summary of the techniques available to them, and the evidence base for their use when managing nerve transection including current use and applicability of nerve transfer procedures.

Advancing Our Understanding of the Chronically Denervated Schwann Cell: A Potential Therapeutic Target?

Outcomes for patients following major peripheral nerve injury are extremely poor. Despite advanced microsurgical techniques, the recovery of function is limited by an inherently slow rate of axonal regeneration. In particular, a time-dependent deterioration in the ability of the distal stump to support axonal growth is a major determinant to the failure of reinnervation. Schwann cells (SC) are crucial in the orchestration of nerve regeneration; their plasticity permits the adoption of a repair phenotype following nerve injury. The repair SC modulates the initial immune response, directs myelin clearance, provides neurotrophic support and remodels the distal nerve. These functions are critical for regeneration; yet the repair phenotype is unstable in the setting of chronic denervation. This phenotypic instability accounts for the deteriorating regenerative support offered by the distal nerve stump. Over the past 10 years, our understanding of the cellular machinery behind this repair phenotype, in particular the role of c-Jun, has increased exponentially, creating opportunities for therapeutic intervention. This review will cover the activation of the repair phenotype in SC, the effects of chronic denervation on SC and current strategies to 'hack' these cellular pathways toward supporting more prolonged periods of neural regeneration.