AB106. Role of Schwann cells in the regeneration of penile and peripheral nerves

Abstract

Schwann cells (SCs) are the principal glia of the peripheral nervous system. The end point of SC development is the formation of myelinating and non-myelinating cells which ensheath large and small diameter axons, respectively. They play an important role in axon regeneration after injury, including cavernous nerve injury that leads to erectile dysfunction (ED). Although surgical techniques for radical prostatectomy (RP) for the treatment of prostate cancer have improved with the introduction of nerve-sparing techniques and robotic procedures, many patients still suffer from ED following surgery. During surgery trauma causes traction injury and local inflammatory changes in the neuronal microenvironment of the autonomic fibers innervating the penis resulting pathophysiological alterations in the end organ. The suggested pathophysiologic mechanisms responsible for RP-induced ED include: reduction in neuronal nitric oxide synthase (nNOS), a decrease in the number of cavernous endothelial and smooth muscle cells, increase in reactive oxygen species, and up-regulation of profibrotic factors and cavernous fibrosis as a result of cavernous hypoxia. Current research strategies to prevent ED following RP have focused on pharmacological interventions, such as PDE5 inhibitors, that prevent penile corporal fibrosis in an effort to preserve the hemodynamic mechanisms of penile erection. However, a number of patients with RP-induced ED do not respond well to such pharmacological intervention suggesting a need for novel therapies. Currently there are no interventions targeted at cavernosal nerve regeneration because the mechanisms of regeneration including demyelination, axon degeneration, re-myelination, SC and neuron interaction, the molecular signaling process is poorly understood. For decades SCs received relatively little scientific attention with poor understanding of their function despite the fact that they outnumber the neurons in the peripheral nerve system (PNS) and are involved in almost all neural functions. New technologies available to neurobiologists have now provided unexpected insight into SC function and have greatly expanded research.