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Transdermal delivery of 4-aminopyridine accelerates motor functional recovery and improves nerve morphology following sciatic nerve crush injury in mice

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Neural Regeneration Research 2020年第1期15卷 136-144页

作者： Andrew RClark Chia George Hsu M A Hassan Talukder Mark Noble john celfar Center for Orthopaedic Research and Translational Science Penn State Hershey College of MedicineMilton S.Hershey Medical CenterHersheyPAUSA Department of Orthopaedics The University of Rochester Medical CenterRochesterNYUSA Department of Medicine Aab Cardiovascular Research InstituteUniversity of Rochester School of Medicine and DentistryRochesterNYUSA Department of Biomedical Genetics The University of Rochester Medical CenterRochesterNYUSA

Oral 4-aminopyridine(4-AP)is clinically used for symptomatic relief in multiple sclerosis and we recently demonstrated that systemic 4-AP had previously unknown clinically-relevant effects after traumatic peripheral nerve injury including the promotion of re-myelination,improvement of nerve conductivity,and acceleration of functional *** hypothesized that,instead of oral or injection administration,transdermal 4-AP(TD-4-AP)could also improve functional recovery after traumatic peripheral nerve *** with surgical traumatic peripheral nerve injury received TD-4AP or vehicle alone and were examined for skin permeability,pharmacokinetics,functional,electrophysiological,and nerve morphological properties.4-AP showed linear pharmacokinetics and the maximum plasma 4-AP concentrations were proportional to TD-4-AP *** a single dose of TD-4-AP administration demonstrated rapid transient improvement in motor function,chronic TD-4-AP treatment significantly improved motor function and nerve conduction and these effects were associated with fewer degenerating axons and thicker myelin sheaths than those from vehicle *** findings provide direct evidence for the potential transdermal applicability of 4-AP and demonstrate that 4-AP delivered through the skin can enhance in-vivo functional recovery and nerve conduction while decreasing axonal *** animal experiments were approved by the University Committee on Animal Research(UCAR)at the University of Rochester(UCAR-2009-019)on March 31,2017.

关键词： 4-aminopyridine electron microscopy functional recovery nerve conduction velocity peripheral nerve injury pharmacokinetics transdermal administration

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