4-Aminopyridine promotes functional recovery and remyelination in acute peripheral nerve injury

Kuang Ching Tseng, Haiyan Li, Andrew Clark, Leigh Sundem, Michael Zuscik, Mark Noble, John Elfar

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1409-1420
Number of pages12
JournalEMBO Molecular Medicine
Volume8
Issue number12
DOIs
StatePublished - Dec 1 2016

All Science Journal Classification (ASJC) codes

  • Molecular Medicine

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