PATHOLOGICAL AND BIOCHEMICAL CONSEQUENCES OF ACUTE AND CHRONIC NEUROINFLAMMATION WITHIN THE BASAL FOREBRAIN CHOLINERGIC SYSTEM OF RATS

Inflammatory processes may play a critical role in the degeneration of basal forebrain cholingeric cells that underlies some of the cognitiv e impairments associated with Alzheimer's disease. In the present stud y, the proinflammagen lipopolysaccharide, from the cell wall of Gram-n egative bacteria, was used to produce inflammation within the basal fo rebrain of rats. The effects of acute, high-dose injections of lipopol ysaccharide (2, 20 or 40 mu g) upon basal forebrain chemistry and neur onal integrity were compared with the effects of chronic, low-dose lip opolysaccharide infusions (0.18, 0.25, 1.8 or 5.0 mu g/h) for either 1 4, 37, 74 or 112 days. Acute exposure to lipopolysaccharide decreased cortical choline acetyltransferase activity and the number of immunore active choline acetyltransferase-positive cells within a small region of the basal forebrain. Regional levels of five different neuropeptide s were unchanged by acute, high-dose lipopolysaccharide injections. Ch ronic lipopolysaccharide infusions produced (i) a time-dependent, but not dose-dependent, decrease in cortical choline acetyltransferase act ivity that paralleled a decline in the number of choline acetyltransfe rase- and p75-immunoreactive cells within the basal forebrain, and (ii ) a dense distribution of reactive astrocytes and microglia within the basal forebrain. Chronic neuroinflammation might underlie the genesis of some neuropathological changes associated with normal ageing or Al zheimer's disease. (C) 1998 IBRO. Published by Elsevier Science Ltd.