The earlier period changes of dopaminergic neurons and glial cells in intracephalic inflammation rat model induced by intracerebreventricular injection of lipopolysaccharide

Objective To create an intracephalic inflammation rat model induced by intracerebroventricular injection of lipopolysaccharide(LPS)and investigate the earlier-period changes of glial cells and effect of inflammation on dopaminergic(DA)neurons in the substantia nigra,in order to explore the role of inflammation in the process of dopaminergic neurons degeneration.Methods 36 healthy male SD rats were randomly divided into six groups.All injections were made intracerebroventricularly on right side with LPS 20 μl(5 mg/ml)or saline 20 μl.At 1,6,24 h after injection of LPS or saline,specific antibody OX-42 and GFAP were separately used to detect the changes in morphology and the numbers of microglia and astrocytes in the whole rat brain;at the same time,the changes of substantia nigra DA neurons were observed by tyrosine-hydroxylase(TH)immunohistochemical staining.Results At 1 h after injection of LPS,OX-42-positive microglia in hippocampus and striatum were activated,while OX-42-positive microglia in substantia nigra still exhibited typically ramified resting stage.At 6 and 24 h post-injection,all OX-42-positive microglia in hippocampus,striatum and substantia nigra were all activated and appeared to be bushy or amoeboid.However,at 1,6,24 h after LPS injection,the GFAP-positive immunoreactivity in LPS injection rats showed no obvious difference compared to that of the control rats.Similarly,compared to the control group,the number of TH-positive neurons in substantia nigra did not decrease significantly at 1,6 and 24 h after LPS injection.Conclusions The intracephalic inflammation rat model could be made successfully by a single intracerebroventricular(ICV)administration of LPS.In this rat model,microglia is activated immediately after LPS injection,while intracephalic inflammation has no effect on dopaminergic neurons within 24 h.