Brain inflammatory response induced by intracerebroventricular infusion of lipopolysaccharide: an immunohistochemical study

Inflammatory processes may play a critical role in the pathogenesis of the degenerative changes associated with Alzheimer's disease (AD). In the present study, we used an animal model of brain inflammation in order to study a possible mechanism involved in AD. Lipopolysaccharide (LPS) was used to produce global microglial reactivity within the brain of young rats, Time-dependent changes in the inflammatory reaction and the participation of glial cells after acute injection of LPS (50 or 100 mu g) into the lateral ventricle or the fourth ventricle were compared with the chronic infusion of LPS (0.15, 0.5, 1.5 or 5.0 mu g/h) into the fourth ventricle (14 days). Several immunohistochemical markers were used to characterize the microglial response. Acute and chronic exposure to LPS induced major histocompatibility complex class II (MHC II) antigen expression, detected with OX-6 antibody, in a sub-population of microglial cells in defined brain areas. The morphological features and distribution of OX-6 positive cells observed in the proximity of the cannula track after LPS injection into the lateral ventricle suggested the recruitment of monocytes/macrophages from the periphery. The activation of the resident microglial cells was delayed and mainly concentrated within the temporal lobe regions and the limbic system. Chronic infusion to LPS into the fourth ventricle induced a comparable activation of microglial cells. Quantitative analysis of OX-6 positive cells showed a dose-dependent response to LPS exposure. (C) 1998 Elsevier Science B.V. All rights reserved.