Orally administered boldine reduces muscle atrophy and promotes neuromuscular recovery in a rodent model of delayed nerve repair

Frontiers in Cellular Neuroscience, 2023 · DOI: 10.3389/fncel.2023.1240916 · Published: September 27, 2023

Regenerative Medicine Neurology Genetics

Simple Explanation

Peripheral nerve injury often results in poor functional recovery due to a prolonged period of muscle denervation. The study investigated the effects of orally administered boldine, a connexin hemichannel inhibitor, on denervated-related muscle changes and nerve regeneration in a rat model of delayed peripheral nerve repair. Findings suggest that boldine may be a promising pharmacological approach to minimize the deleterious effects of prolonged denervation and, with further optimization, may improve levels of functional recovery following nerve repair.

Study Duration

10 weeks

Participants

Male Sprague–Dawley rats (300–330 g; aged 6–8 weeks)

Evidence Level

Not specified

Key Findings

1
Daily boldine administration significantly enhanced an evoked response in the tibialis anterior muscle at 2 weeks after common peroneal nerve transection.
2
Boldine administration reduced intramuscular connexin 43/45 expression and muscle fiber atrophy, as well as connexin 43 expression around denervated Schwann cells up to 4 weeks post injury.
3
Reinnervated muscle fiber diameters were larger in boldine-treated animals suggesting enhanced myofiber recovery.

Research Summary

This study assessed the efficacy of daily oral boldine administration in a rodent model of prolonged denervation and delayed nerve repair. Boldine administration preserved the evoked muscle for 2 weeks after injury and mitigated muscle fiber atrophy up to 4 weeks following axotomy. Greater axon myelination, reinnervated muscle fiber diameter, and acetylcholine receptor expression were measured at 6 weeks post repair (10 weeks total from initial transection injury).

Practical Implications

Pharmaceutical Intervention

Boldine shows promise as a pharmacological intervention to mitigate the harmful effects of prolonged denervation following peripheral nerve injury.

Muscle Preservation

Boldine administration can help preserve muscle function and reduce atrophy during the period of denervation before nerve repair.

Enhanced Recovery

Boldine may promote early maturation of regenerated axons and enhance neuromuscular functional recovery after delayed nerve repair.

Study Limitations

1
Boldine has a short half-life, requiring further studies to determine optimal dosing and timing.
2
Dosage studies are needed in large animal models to establish a safe and effective dose range.
3
Additional preclinical testing is necessary to determine the mechanism(s)-of-action and evaluate functional recovery.

Your Feedback

Was this summary helpful?

Back to Regenerative Medicine