Early and delayed effects of omega-3 polyunsaturated fatty acids on peripheral nerve regeneration

Peripheral nerve injury can result in significant functional impairment and long-term disability, highlighting the need for effective strategies to enhance nerve regeneration. This study investigated the effects of omega-3 fatty acids (10-15% EPA, 8-15% DHA) on peripheral nerve regeneration following experimental sciatic nerve injury. A total of 30 adult male Wistar albino rats (10-14 weeks old, 250-300 g) were randomly divided into five groups (n = 6 per group). The control group (Cont) received no intervention, while the crush injury group (CI) underwent a 60-second sciatic nerve crush without supplementation. Omega-3 supplementation (300 mg/kg/day) was administered at different time points: prior to injury (CIW1), immediately after injury (CIW2), and delayed post-injury starting 15 days after injury (CIW3). At the end of the experimental period, sciatic nerves were evaluated using functional assessment, stereological analysis, and light and electron microscopy. In addition, potential molecular interactions related to nerve regeneration were explored using the STRING database. Omega-3 supplementation significantly increased myelin sheath thickness in all treatment groups compared with the untreated crush injury group. Axonal area was markedly increased in the delayed supplementation group (CIW3), and the total number of axons in the untreated crush group remained lower than in the omega-3-treated groups. These findings suggest that omega-3 fatty acids may promote remyelination and structural recovery following peripheral nerve injury and could represent a potential therapeutic adjunct for enhancing peripheral nerve regeneration.