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 o rder to study a possible mechanism involved in AD. Lipopolysaccharide (LPS) was used to produce global microglial reactivity within the brai n of young rats, Time-dependent changes in the inflammatory reaction a nd the participation of glial cells after acute injection of LPS (50 o r 100 mu g) into the lateral ventricle or the fourth ventricle were co mpared 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 mark ers were used to characterize the microglial response. Acute and chron ic exposure to LPS induced major histocompatibility complex class II ( MHC II) antigen expression, detected with OX-6 antibody, in a sub-popu lation of microglial cells in defined brain areas. The morphological f eatures and distribution of OX-6 positive cells observed in the proxim ity of the cannula track after LPS injection into the lateral ventricl e suggested the recruitment of monocytes/macrophages from the peripher y. The activation of the resident microglial cells was delayed and mai nly concentrated within the temporal lobe regions and the limbic syste m. Chronic infusion to LPS into the fourth ventricle induced a compara ble activation of microglial cells. Quantitative analysis of OX-6 posi tive cells showed a dose-dependent response to LPS exposure. (C) 1998 Elsevier Science B.V. All rights reserved.