Background: Loss of dopaminergic neurons in the substantia nigra (SN) results in Parkinson's disease (PD). Rotenone is used as an animal model of PD. BM-MSCs are a promising therapy.

The work aimed to evaluate the effects of rotenone on the SN and the role of BM-MSCs in ameliorating these effects.

Material and methods: A total number of 24 rats were randomly divided into three groups. Group A was subdivided into; group A1 (6 rats) received a subcutaneous injection of 5 ml/kg DMSO every 2 days for two weeks and group A2 (6 rats) received the same regimen for five weeks. Group B (rotenone-treated group) (6 rats) received a subcutaneous injection of a dose of 1.5 mg/kg rotenone dissolved in 5 ml of DMSO/kg, once every 2 days for two weeks. Group C (BM-MSCs-treated group) (6 rats) was injected with rotenone with the same regimen as group B, followed by an intraperitoneal injection of one million heterogenous BM-MSCs diluted with 1 ml of saline and sacrificed 3 weeks later. At the destined time, the rats were sacrificed, and the brains were processed for light and electron microscopic examination and immunohistochemistry.

Results: Group B showed statistically significant decrease in the body weight and increase in the brain weight in comparison to the control group A1, signs of neuronal degeneration, Lewy bodies, destructed neuronal ultrastructure, increased immunoreactivity of GFAP and caspase-3, and protein aggregation in the ubiquitin study. Group C showed noticeable morphometric, histological, and immunological improvement.

Conclusion: The rotenone negatively affects the substantia nigra, and the BM-MSCs could ameliorate these effects.