Peripheral administration of lipopolysaccharide induces activation of microglial cells in rat brain

Abstract

Using immunocytochemistry with monoclonal antibodies against surface immunomolecules and Griffonia simplicifolia lectin histochemistry, the microglial cell reaction in rat brain was studied after intravenous injection of lipopolysaccharide (LPS). Activation of microglial cells throughout the brain became apparent within hours and peaked at 8-24 h following 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 ramified microglia to round, macrophage-like cells in the anterior hypothalamus, thalamus and the brainstem. After injection of 1 mg/kg LPS, this morphological transition was only detected in the brainstem. Microglial cell reactivity gradually returned to control levels within 7 days after LPS administration. Furthermore, LPS induced enhanced expression of 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 injection of LPS. Despite the presence of highly activated microglial cells in the rat brain, no signs of tissue damage were observed at any time point after injection of LPS examined. In addition to the activation of microglial cells, intravenous injection of LPS induced accumulations of macrophages in blood vessels of the choroid plexus and the brain, but no disruption of vessels with subsequent invasion of parenchyma by blood macrophages was detected. Our data demonstrate that a peripheral immune challenge leads to a high and transitory activation of microglial cells in the brain which could possibly contribute to the pathology of infections and septic shock.