title: 4-Aminopyridine promotes functional recovery and remyelination in acute peripheral nerve injury.
abstract: Traumatic peripheral nerve damage is a major medical problem without effective treatment options. In repurposing studies on 4-aminopyridine (4-AP), a potassium channel blocker that provides symptomatic relief in some chronic neurological afflictions, we discovered this agent offers significant promise as a small molecule regenerative agent for acute traumatic nerve injury. We found, in a mouse model of sciatic crush injury, that sustained early 4-AP administration increased the speed and extent of behavioral recovery too rapidly to be explained by axonal regeneration. Further studies demonstrated that 4-AP also enhanced recovery of nerve conduction velocity, promoted remyelination, and increased axonal area post-injury. We additionally found that 4-AP treatment enables distinction between incomplete and complete lesions more rapidly than existing approaches, thereby potentially addressing the critical challenge of more effectively distinguishing injured individuals who may require mutually exclusive treatment approaches. Thus, 4-AP singularly provides both a new potential therapy to promote durable recovery and remyelination in acute peripheral nerve injury and a means of identifying lesions in which this therapy would be most likely to be of value.
authors.affiliation: Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA.|Department of Chemical Engineering, University of Rochester, Rochester, NY, USA.
authors.forename: Kuang-Ching
authors.initials: KC
authors.lastname: Tseng
authors.affiliation: Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA.|Department of Orthopaedics & Rehabilitation, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Orthopaedics & Rehabilitation, University of Rochester Medical Center, Rochester, NY, USA.|Department of Biomedical Engineering, University of Rochester, Rochester, NY, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Clark
authors.affiliation: Department of Orthopaedics & Rehabilitation, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Leigh
authors.initials: L
authors.lastname: Sundem
authors.affiliation: Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA.|Department of Orthopaedics & Rehabilitation, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Zuscik
authors.affiliation: Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA mark_noble@urmc.rochester.edu openelfar@gmail.com.
authors.forename: Mark
authors.identifier: 0000-0002-2375-7773
authors.initials: M
authors.lastname: Noble
authors.affiliation: Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA mark_noble@urmc.rochester.edu openelfar@gmail.com.|Department of Orthopaedics & Rehabilitation, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: John
authors.initials: J
authors.lastname: Elfar
mesh_terms: D015761:4-Aminopyridine / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D051379:Mice; D009431:Neural Conduction / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D059348:Peripheral Nerve Injuries / Q000188:drug therapy*; D026902:Potassium Channel Blockers / Q000627:therapeutic use*; D020426:Sciatic Neuropathy / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D026902:Potassium Channel Blockers; D015761:4-Aminopyridine
keywords: 4‐aminopyridine; localized delivery; nerve conduction velocity; peripheral nerve injury; remyelination