Ivermectin Promotes Peripheral Nerve Regeneration during Wound Healing

Area of Science:

• Neuroscience
• Regenerative Medicine
• Pharmacology

Background:

• Peripheral nerve regeneration relies on Schwann cells, which create a supportive microenvironment for neuronal regrowth.
• Impaired Schwann cell response hinders nerve repair, necessitating novel strategies to enhance regeneration, particularly in humans.
• Ivermectin has shown potential in promoting nerve repair, as evidenced by its effect on eye tissue in *Xenopus laevis* tadpoles.

Purpose of the Study:

• To investigate the role of ivermectin in mammalian peripheral nerve repair.
• To determine if ivermectin can enhance nerve regeneration by modulating fibroblast behavior.

Main Methods:

• In vitro co-culture assays using human induced neural stem cells (hiNSCs) and human dermal fibroblasts (hDFs).
• Characterization of ivermectin's effects on hDFs, including glutamate uptake, neurotrophic factor secretion, morphology, and glial marker expression.
• In vivo studies involving localized ivermectin treatment in dermal wound sites to assess nerve regeneration markers.

Main Results:

• Ivermectin-treated hDFs promoted hiNSC proliferation and migration in vitro.
• Ivermectin induced hDFs to exhibit glia-like characteristics: increased glutamate uptake, secretion of glial cell-derived neurotrophic factor, elongated morphology, and glial fibrillary acidic protein expression.
• In vivo, ivermectin treatment upregulated glial and neuronal markers during wound healing.

Conclusions:

• Ivermectin effectively promotes peripheral nerve regeneration in mammals.
• The drug achieves this by inducing fibroblasts to acquire a glia-like phenotype, thereby supporting nerve repair.
• Ivermectin represents a promising therapeutic agent for enhancing nerve regeneration.