4-aminopyridine promotes accelerated skin wound healing via neurogenic-mediator expression

Abstract

We discovered that 4-aminopyridine (4-AP), a potassium channel blocker approved by the FDA for improving walking ability in multiple sclerosis, greatly enhances skin wound healing. Benefits included faster wound closure, restoration of normal-appearing skin architecture, increased vascularization and reinnervation. Hair follicle neogenesis within the healed wounds was increased, both histologically and by analysis of K15 and K17 expression. 4-AP increased levels of vimentin (fibroblasts) and -smooth muscle actin (-SMA, collagen-producing myofibroblasts) in the healed dermis. 4-AP also increased neuronal regeneration with increased numbers of axons and S100+ Schwann cells (SCs), and increased expression of SRY-Box Transcription Factor 10 (SOX10). Treatment also increased levels of transforming growth factor-{beta} (TGF-{beta}), substance P and nerve growth factor (NGF), important promoters of wound healing. In-vitro studies demonstrated that 4-AP enhanced proliferation and migration of human keratinocytes and SCs, and that 4-AP enhanced cellular interactions between neuronal and non-neuronal cells to further accelerate wound healing. Thus, 4-AP enhanced many of the key attributes of successful wound healing and offers a promising new approach to enhance skin wound healing and tissue regeneration.