Abstract
Background
Peripheral nerve repair is considered the gold standard treatment for complete nerve
transection injuries, yet achieving satisfactory functional recovery remains challenging
due to muscle atrophy during the time required for axonal regeneration. This study
investigated the beneficial effects of 4-aminopyridine (4-AP), a potassium channel
blocker, on neural and muscular recovery.
Methods
Following complete transection of the right sciatic nerve, 40 mice underwent end-to-end
nerve repair using microscopic epineural sutures and were randomly assigned to either
the control or 4-AP groups immediately after surgery (n = 20 per group). The experimental animals were administered intraperitoneal injections
of 200 μL normal saline or soluble 4-AP at a dose of 10 μg daily. The sciatic functional
index (SFI) and nerve conduction studies were measured until 12 weeks postoperatively.
Morphological analyses of nerve and muscle, and Western blotting for proteins associated
with muscle atrophy were performed at 3 and 12 weeks after surgery.
Results
There were no significant differences in the SFI between the two groups. Nerve conduction
study showed that 4-AP treatment increased the compound muscle action potential and
decreased latency. A histomorphometric study showed that 4-AP treatment increased
myelin thickness, G-ratio (axonal diameter/axoglial diameter on cross-sectioned nerve),
cross-sectional area of myofibrils, and minimal Feret diameter of myofibrils. Additionally,
expression levels of FoxO3 and mTORC1 were lower in the 4-AP treated mice, while myogenin
expression levels showed no significant difference between the groups.
Conclusion
4-AP treatment promotes myelination and prevents denervation-induced muscle atrophy
after neurorrhaphy. These findings suggest that 4-AP may be a promising candidate
for clinical consideration as an adjuvant therapy following nerve repair for transection
injuries.
Keywords
peripheral nerve - nerve injury - nerve regeneration - muscle atrophy - nerve repair
- neurorrhaphy - 4-aminopyridine - 4-AP
