The expression of tumour necrosis factor in the hypothalamus after treatment with lipopolysaccharide

To investigate the effects of tumour necrosis factor (TNF) in the hypothalamus, Wistar rats received an intravenous administration of lipopolysaccharide (LPS) at a dose of 3.0 mg/100 g. Concentrations of TNF-alpha in the cerebral liquor and blood sera rapidly increased at 30 minutes after administration of LPS, rose to the maximum level at 1 hour, and then gradually decreased. Using horse-radish peroxidase as a tracer, a transient increase in paracellular permeability throughout the tight junctions of the ependymal cell layer covering the third ventricle was observed by electron microscopy at 30 minutes and in that of the capillary endothelium at 1 hour after administration, respectively. Following LPS administration, TNF was preferentially localized by immunoelectron microscopy in the tight junctional area of the ependymal cell layer and the capillary. These data indicate that TNF, synthesized in the ependymal cell layer, induces a deterioration in the cerebrospinal fluid-brain barrier and subsequently in the blood-brain barrier. The present study suggests that oedematous changes in the hypothalamic areas determined by ultrastructural and magnetic resonance analyses were mainly due to TNF conveyed from the ependymal cell layer to the hypothalamus after administration of LPS.