title: Pathways regulating modality-specific axonal regeneration in peripheral nerve.
abstract: Following peripheral nerve injury, the distal nerve is primed for regenerating axons by generating a permissive environment replete with glial cells, cytokines, and neurotrophic factors to encourage axonal growth. However, increasing evidence demonstrates that regenerating axons within peripheral nerves still encounter axonal-growth inhibitors, such as chondroitin sulfate proteoglycans. Given the generally poor clinical outcomes following peripheral nerve injury and reconstruction, the use of pharmacological therapies to augment axonal regeneration and overcome inhibitory signals has gained considerable interest. Joshi et al. (2014) have provided evidence for preferential or modality-specific (motor versus sensory) axonal growth and regeneration due to inhibitory signaling from Rho-associated kinase (ROCK) pathway regulation. By providing inhibition to the ROCK signaling pathway through Y-27632, they demonstrate that motor neurons regenerating their axons are impacted to a greater extent compared to sensory neurons. In light of this evidence, we briefly review the literature regarding modality-specific axonal regeneration to provide context to their findings. We also describe potential and novel barriers, such as senescent Schwann cells, which provide additional axonal-growth inhibitory factors for future consideration following peripheral nerve injury.
authors: Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, Campus Box 8238, 660 South Euclid Avenue, St. Louis, MO 63110, USA. Electronic address: woodm@wudosis.wustl.edu.
authors: Matthew D
authors: MD
authors: Wood
authors: Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, Campus Box 8238, 660 South Euclid Avenue, St. Louis, MO 63110, USA. Electronic address: mackinnon@wudosis.wustl.edu.
authors: Susan E
authors: SE
authors: Mackinnon
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D006801:Humans; D009416:Nerve Regeneration / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D059348:Peripheral Nerve Injuries / Q000175:diagnosis / Q000503:physiopathology; D010525:Peripheral Nerves / Q000502:physiology*
keywords: Axon modality; Chondroitin sulfate proteoglycan; Motor neuron; Nerve regeneration; Peripheral nerve; ROCK; RhoA; Schwann cell; Sensory neuron; Y-27632