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3-Methyl-4-Aminopyridine Enhances Functional and Electrophysiological Recovery Following Sciatic Nerve Crush in Mice
Julia Chrisbacher
*2, Margaret Beha
1, Njima Schläpfer
1, Remy Liechti
1, Jonathan Leckenby
11Division of Plastic & Reconstructive Surgery, University of Rochester Medical Center, Rochester, NY; 2University of Rochester School of Medicine & Dentistry, Rochester, NY
Background: Peripheral nerve injuries cause significant morbidity, and pharmacologic strategies to enhance nerve regeneration remain limited. A potassium channel blocker, 4-aminopyridine (4AP), promotes nerve recovery, but data on its derivatives, 3-methyl-4AP (3Me4AP) and 3-methoxy-4AP (3MeOx4AP), are sparse. This study compares their effects on recovery following sciatic nerve crush in mice.
Methods: C57BL/6J mice (n=6/group) underwent sciatic nerve crush. Mice received daily intraperitoneal injections (1 mg/kg) of PBS, 4AP, 3Me4AP, or 3MeOx4AP for 12 weeks. Functional recovery was assessed using the sciatic function index (SFI) and electrophysiological outcomes (CMAP amplitude, latency, conduction velocity) at baseline and at weeks 3, 6, 9, and 12. Statistical analyses included two-way ANOVA with Tukey's HSD and mixed-effects modeling.
Results: Gait analysis showed significantly higher SFI in the 3Me4AP group at weeks 6, 9, and 12, when compared to controls (p<0.001; p<0.001; p<0.05). The 4AP group demonstrated a significant improvement in SFI only at week 9 (p<0.05). CMAP amplitude was higher in the 3Me4AP group at weeks 3, 6, and 12 compared to controls (p<0.05; p<0.001; p<0.001). Of note, the increase in amplitude for 3Me4AP approached significance at week 9 (p=0.055). No other group demonstrated improvement in CMAP amplitude. Latency and conduction velocity did not differ between controls and treatment groups.
Conclusion: In this model of sciatic nerve crush, daily administration of 3Me4AP significantly improved functional recovery (SFI) and enhanced CMAP amplitude across multiple time points. Treatment with 4AP produced only transient functional improvement without electrophysiological benefits. Neither latency nor conduction velocity differed from controls in any treatment group. These findings suggest 3Me4AP may have superior efficacy over 4AP in promoting nerve recovery following a crush injury, potentially due to its enhanced lipophilicity, which may contribute to greater tissue penetrance.
Models adjusted for BMI, tissue expander size, and axillary irradiation. OR > 1 indicates higher odds with early exchange.
Back to 2026 Abstracts
Models adjusted for BMI, tissue expander size, and axillary irradiation. OR > 1 indicates higher odds with early exchange.
