The "Double-Hit" Model in Experimental Parkinsonism: Effects of Combined Exposure to Lactacystin and LPS

The present study aimed to investigate a "double-hit" model of Parkinson's disease, implying intranigral administration of lactacystin and intraperitoneal injection of LPS. The model group rats exhibited significant deterioration in several parameters of the motor function (p ⩽ 0.04) and emotional impairment (p ⩽ 0.04) compared to the control. Morphological signs of neurodegeneration (p ⩽ 0.001) and microglial activation (p ⩽ 0.02) were observed in the substantia nigra. These findings support the utility of this "double-hit" model for elucidating the mechanisms underlying parkinsonism and for preclinical testing of candidate therapeutics.