Effects of chronic intrahippocampal infusion of lipopolysaccharide in the rat

Abstract Astrogliosis and microglial activation are associated with many neurodegenerative disorders including multiple sclerosis, its animal model experimental allergic encephalomyelitis, and Alzheimer's disease. To address the hypothesis that chronic astroglial or microglial activation could be contributing factors to neuronal death or injury, the immunostimulant lipopolysaccharide was infused into the hippocampus for 16 days using Alzet mini-osmotic pumps attached to a cannula. Placement of the cannula and infusion of vehicle for 16 days caused a hippocampal lesion with a volume of 0.5 ± 0.1 mm 3 . Infusion of lipopolysaccharide at the dose of 2.0 μg/day produced a lesion of 4.9 ± 1.3 mm 3 ( P 3 ( P Under the experimental conditions employed in the present study, chronic infusion of lipopolysaccharide into the hippocampus resulted in a dose-dependent focal necrotic lesion at the site of infusion. In tissue surrounding the encapsulated lesion, neurons were present among the reactive astrocytes and increased number of macrophages suggesting that astrocytes and macrophages can be activated without causing neuronal loss.