PERIPHERAL ADMINISTRATION OF LIPOPOLYSACCHARIDE INDUCES ACTIVATION OFMICROGLIAL CELLS IN RAT-BRAIN

Using immunocytochemistry with monoclonal antibodies against surface i mmunomolecules and Griffonia simplicifolia lectin histochemistry, the microglial cell reaction in rat brain was studied after intravenous in jection of lipopolysaccharide (LPS). Activation of microglial cells th roughout the brain became apparent within hours and peaked at 8-24 h f ollowing administration of 1, 2.5 and 5 mg/kg LPS. High doses of LPS ( 2.5 and 5 mg/kg) induced a morphological transition of resting ramifie d microglia to round, macrophage-like cells in the anterior hypothalam us, thalamus and the brainstem. After injection of 1 mg/kg LPS, this m orphological transition was only detected in the brainstem. Microglial cell reactivity gradually returned to control levels within 7 days af ter LPS administration. Furthermore, LPS induced enhanced expression o f MHC class II by microglial cells. Maximal up-regulation of MHC class II Ia-antigen was found 3 days following injection of LPS, and only a few highly Ia immunoreactive cells were detectable 7 days following i njection of LPS. Despite the presence of highly activated microglial c ells in the rat brain, no signs of tissue damage were observed at any time point after injection of LPS examined. In addition to the activat ion of microglial cells, intravenous injection of LPS induced accumula tions of macrophages in blood vessels of the choroid plexus and the br ain, but no disruption of vessels with subsequent invasion of parenchy ma by blood macrophages was detected. Our data demonstrate that a peri pheral immune challenge leads to a high and transitory activation of m icroglial cells in the brain which could possibly contribute to the pa thology of infections and septic shock. Copyright (C) 1996 Elsevier Sc ience Ltd.