Synergistic Effects of Cerebrolysin and Aerobic Exercise on 6-hydroxydopamine-induced Model of Parkinson Disease in Adult Male Rats

Introduction: Neurotrophic factors and physical activities have beneficial effects on neurodegenerative disorders.This study assessed the impact of physical exercise (EXE) and cerebrolysin (CBL), individually or in combination, in a Parkinson's disease (PD) model caused by 6-hydroxydopamine (6-OHDA). Methods:The study utilized 62 male Wistar rats, which were divided into six groups (n=12): Sham (received intra substantia nigra [SN] injection of normal saline), PD (underwent 12.5 g injection of 6-OHDA into the left SN), PD+levodopa (treated with levodopa; 12 mg/kg, gavage, for three weeks), PD+CBL (treated with intraperitoneal injection of CBL 2.5 mL/ kg, for three weeks), PD+EXE (exercised 30 min/d for three weeks), and PD+CBL+EXE.Rotation with apomorphine and Murprogo's test was assessed 21 days after PD induction and after treatments.Ultimately, the levels of lipid peroxidation marker and total antioxidant capacity (TAC), glutathione peroxidase (GPx) activity, -synuclein protein expression, and histopathological changes of the SN were evaluated ipsilateral to the lesioned side. Results:The results showed that CBL and exercise, alone or in combination, decreased ipsilateral apomorphine rotation and muscle rigidity in the PD animals.Moreover, these behavioral changes were associated with reduced malondialdehyde (MDA) levels and -synuclein protein levels, increased TAC level and GPx activity, and a greater neuronal count in the SN.Notably, the combination effects were greater than single therapy and levodopa treatment. Conclusion:Our findings indicate that the combination of exercise and CBL ameliorated 6-OHDA-induced motor impairments by attenuating oxidative stress and protein expression of -synuclein and preserving neurons in the SN.