The single intranigral injection of LPS as a new model for studying the selective effects of inflammatory reactions on dopaminergic system

We have injected lipopolysaccharide (LPS) into the nigrostriatal pathway of rats in order to address the role of inflammation in Parkinson's disease ( PD). LPS induced a strong macrophage/microglial reaction in Substantia nigr a (SN), with a characteristic clustering of macrophage cells around bloodve ssels. The SN was far more sensitive than the striatum to the inflammatory stimulus. Moreover, only the dopaminergic neurons of the SN were affected, with no detectable damage to either the GABAergic or the serotoninergic neu rons. The damage to the DA neurons in the SN was permanent, as observed 1 y ear postinjection. Unlike the direct death of dopaminergic neurons caused b y agents as MPP+ or 6-OHDA, LPS seems to cause indirect death due to inflam matory reaction. Therefore, we suggest that the injection of a single dose of LPS within the SN is an interesting model for studying the selective eff ects of inflammatory reaction on dopaminergic system and also potentially u seful for studying PD. (C) 2000 Academic Press.