Activation of microglia and dopaminergic neurons degeneration following intraventricular injection of LPS in the substantia nigra of rats

Objective To investigate the effect of intraventricular injection of lipoplysaccharide(LPS) on microglia activation and dopaminergic(DA) neurons in the substantia nigra of rats and to explore the role of intracephalic inflammation on DA neurons chronic degeneration. Methods 30 healthy male SD rats were randomly assigned into normal saline(NS) control group and 50 μg LPS group.The rats were treated with intraventricularl injection of 20 μL NS or 50 μg LPS on right side.40 weeks later,OX-42 and OX-6 antibodies were used to detect whether the microglia were activated in the substantia nigra of rats.The morphology and numbers of DA neurons were observed by tyrosine hydroxylase(TH) immunohistochemical staining.The degenerated neurons were detected by using Fluoro-Jade B(FJB). Results (1) At 40 weeks after injection,the OX-42 positive microglia in the substantia nigra of NS control group rats were quiescing with pale staining.There were numerous activated,darkly stained OX-42 positive microglia in the substantia nigra of 50 μg LPS group rats.OX-6 positive microglia were not found in both of the two groups.(2) There were numerous darkly stained TH-positive neurons in the substantia nigra of NS control group.The number of TH-positive neurons in the 50 μg LPS group rats(99.11±20.31) decreased by 47.7%(t=4.445,P0.01) compared with that of NS control group(189.52±12.12).(3) There were no FJB positive neurons in the substantia nigra of both the two group rats. Conclusions Single intraventricular injection of 50 μg LPS may induce long-term chronic activation of microglia and chronic delayed functional injury to the DA neurons in the substantia nigra of rats.