Abstract
Purpose: This study investigated the neuroprotective effects of Cerebrolysin on functional recovery, axonal regeneration, and macrophage polarization in a rat model of traumatic sciatic nerve injury. Methods: Seventy-two male Wistar rats were divided into six groups: sham control, crush injury (control), vehicle-treated crush injury, and two Cerebrolysin-treated crush injury groups (2.5 mg/kg and 5 mg/kg). Functional recovery was assessed using the sciatic functional index (SFI) and hot plate test. Histomorphometry, gastrocnemius muscle mass ratio, Masson's trichrome staining, and immunohistochemistry were used to evaluate axonal regeneration, muscle atrophy, and macrophage polarization, respectively. Results: Results demonstrated that Cerebrolysin, particularly at 5 mg/kg, significantly improved SFI scores and thermal paw withdrawal latency compared to the control group, indicating enhanced functional recovery. Histomorphometric analysis revealed increased myelinated axon counts in the Cerebrolysin-treated groups. Cerebrolysin also mitigated gastrocnemius muscle atrophy and promoted a shift in macrophage polarization from the pro-inflammatory M1 to the pro-healing M2 phenotype. Conclusion: These findings suggest that Cerebrolysin exerts neuroprotective effects in peripheral nerve injury by promoting axonal regeneration, modulating macrophage polarization, and improving functional outcomes. The 5 mg/kg dose demonstrated superior efficacy compared to the 2.5 mg/kg dose. This study highlights the potential of Cerebrolysin as a therapeutic agent for peripheral nerve injuries.