• M A Zito, L A Koennecke, M J McAuliffe, B McNally, N van Rooijen, and M P Heyes.
• Laboratory of Neurotoxicology, Building 10, Room 3D42, National Institute of Mental Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
• Brain Res. 2001 Feb 16; 892 (1): 13-26.

AbstractCNS-localized inflammation with microglial activation and macrophage infiltration contributes to the pathogenesis of a broad spectrum of neurologic diseases. A direct injection of lipopolysaccharide (LPS) into the striatum of gerbils induced lectin-positive macrophage parenchymal invasion, minimal local microglial staining but extensive neurodegeneration (cresyl violet and silver staining) when evaluated 4 days later. In mice, LPS activated microglia (increased lectin staining of morphologically identified cells) with substantially less macrophage invasion but no neurodegeneration was seen at 4 days post LPS infusion. To evaluate the role of infiltrating macrophages in the neurodegenerative response in gerbils, peripheral macrophages were depleted by an intravenous injection of liposome-encapsulated clodronate. This preparation depleted spleen and liver macrophages (>95%), decreased blood monocytes by 55% and attenuated striatal macrophage infiltration (32 to 73% in five representative sections). Notably, the liposome-encapsulated clodronate reduced the severity of LPS-induced neurodegeneration, as visualized by cresyl violet staining and quantified in 20 serially stained silver sections (total volume, 1.32+/-0.41 mm(3) in liposome-encapsulated clodronate-treated versus 3.04+/-0.72 mm(3) in saline-treated controls). These results indicate that a local LPS infusion in gerbil brain may be a useful model in which to investigate the role of invading macrophages and other inflammatory responses in neurodegeneration in inflammatory neurological disease.

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