Long-term neurotoxic effect of intracephalic inflammation on substantia nigra dopaminergic neurons and the changes of asctrocytes in rats / 中华老年医学杂志

ABSTRACT

Objective To investigate the role of asctrocytes in the process of chronic degeneration of dopaminergic neurons in intracephalic inflammation rat model induced by intracerebroventricularly injection of lipopolysaccharide.Methods Sixty healthy male SD rats were assigned into lipopolysaccharide group or saline control group randomly.All injections were made intracerebroventricularly on right side of the rats.Ethovison software was used to measure the movement distance of rats within 30 minutes.Specific antibody for glial fibrillary acid protein (GFAP) was used in immunohistochemistry stain to detect the changes of asctrocytes in the substantia nigra of rats.Results Movement distance of lipopolysaccharide-injected rats decreased by 21.2% compared with saline-injected rats at 16 weeks after injection (t=2.54,P<0.05)by 27.0% (t=3.55,P<0.01) at 24 weeks and by 31.4% (t=3.91,P<0.01) at 28 weeks after lipopolysaccharide injection.The asctrocytes were activated obviously in the substantia nigra of lipopolysaccharide-injected group at 2 weeks,while the numbers of GFAP-positively stained cells (228.60 + 22.35) increased significantly compared with saline-injected group ( 165.20 ± 25.97) (t = 4.14,P< 0.05).The activation of asctrocytes was not found in lipopolysaccharide-injected group at 4 weeks and 12 weeks.The asctrocytes were re-activated in the substantia nigra of lipopolysaccharide-injected group at 24 weeks,while the numbers of GFAP-positively stained cells (220.00±21.01 ) increased significantly compared with saline-injected group (169.00± 19.00) (t= 4.03,P<0.05).The activation of asctrocytes was not seen at any time point in saline-injected group.Conclusions Intracephalic inflammation induces chronic degeneration of substantia nigral dopaminergic neurons in rats.The asctrocytes exhibite "acute activation-quiescing-reactivation" state,indicating that they might be involved in the mechanism of dopaminergic neurons degeneration.