Evaluation of neurotrophic therapies for sciatic nerve injury in mice

Peripheral nerve injuries remain a major therapeutic challenge, frequently resulting in incomplete functional recovery and long-term disability. Although microsurgical repair techniques continue to advance, there is a clear unmet need for adjunctive pharmacological strategies capable of enhancing regenerative outcomes. In this preclinical study, we investigated the functional recovery potential of Calf Blood Hemodialysate, a deproteinized ultrafiltrate enriched with low-molecular-weight peptides and intermediary metabolites, and alpha-lipoic acid (ALA), a potent mitochondrial antioxidant and metabolic modulator. Adult C57BL∕6 mice were randomized into four experimental groups: untreated controls, Calf Blood Hemodialysate-treated (Actovegin), ALA-treated, and combination therapy (Actovegin+ALA). Sciatic nerve injury was induced via the standardized crush injury model, and treatment commenced for 48 hours post-operatively. Calf Blood Hemodialysate was administered intraperitoneally at 200 mg∕kg∕day for 10 days, whereas ALA was delivered at 20 mg∕kg∕day for 14 days. Functional recovery was assessed over a 50-day period using electromyography, the Basso Mouse Scale, and the Beam Walk Test. Immunohistochemical evaluation included analysis of muscle morphology and spinal cord glial fibrillary acidic protein (GFAP) expression. Both monotherapies improved neuromotor performance and electrophysiological outcomes relative to untreated controls. ALA, however, exhibited superior histological and functional benefits, promoting earlier and more sustained recovery compared to Calf Blood Hemodialysate. Notably, combined administration did not produce synergistic effects. Overall, these findings underscore the therapeutic promise of Calf Blood Hemodialysate and ALA in peripheral nerve regeneration and support future investigations utilizing localized delivery platforms, such as gelatin-based hydrogels, to achieve sustained, site-specific release and optimized clinical outcomes.