Therapeutic Effect of Alpha Linolenic Acid on Cutaneous Wound Healing in Hyperglycemic Mice: Involvement of Neurotrophins

<b>Background:</b> Alpha-linolenic acid (ALA) is an essential fatty acid from the omega-3 family that plays an important role in skin homeostasis. It is known for its anti-inflammatory properties, which can contribute to wound healing. Neurotrophins, such as Brain-Derived Neurotrophic Factor (BDNF), may also play an important role in the skin, influencing nerve regeneration and pain modulation. <b>Objectives:</b> This article aims to explore the therapeutic effect of ALA on wound healing in streptozotocin-induced hyperglycemic mice, with an emphasis on the involvement of neurotrophins. <b>Methods:</b> We used keratinocyte cultures exposed or not to ALA and male C57BL6-J mice, which were randomly divided into four groups: non-hyperglycemic treated with vehicle; non-hyperglycemic treated with ALA; hyperglycemic treated with vehicle; and hyperglycemic treated with ALA. The treatment was administered continuously via a subcutaneous osmotic pump. <b>Results:</b> We found that controlled ALA administration potentiates the wound healing process in hyperglycemic mice by accelerating the inflammatory phase and promoting early granulation tissue formation (73.2% ± 0.7 vs. 92.2% ± 2.8 on day 7, n = 5; <i>p</i> < 0.05). This is supported by the balance between the expression of vimentin, CD31, and MMP-9. Furthermore, ALA modulates proteins linked to peripheral neurogenesis and gliogenesis, such as BDNF, NTRK2, SOX-10, CNTF, CTNFR, and STAT-3. It may also promote wound healing and nerve regeneration at the wound site in hyperglycemic animals. In non-hyperglycemic mice, ALA improves the quality of scars but does not accelerate the wound healing process, even with the positive modulation of certain genes relevant to skin healing. <b>Conclusions:</b> Alpha-linolenic acid improves skin wound healing and increases gene expression related to nerve regeneration in wounds of hyperglycemic mice.