DISTRIBUTION OF FOS-LIKE IMMUNOREACTIVITY IN THE RAT-BRAIN FOLLOWING INTRAVENOUS LIPOPOLYSACCHARIDE ADMINISTRATION

The central nervous system, particularly the hypothalamus, is intimate ly involved in the coordination of various aspects of the inflammatory response, including the generation of fever. We used intravenous inje ctions of bacterial cell wall lipopolysaccharide (LPS; 5 or 125 mu g/k g) to stimulate the acute phase response and mapped the resultant dist ribution of Fos-like immunoreactivity in the rat brain. In addition, w e compared the patterns of Fos distribution with the thermoregulatory responses elicited by the LPS. Administration of LPS resulted in a dos e- and time-dependent pattern of Fos-like immunoreactivity throughout the rat brain consistent with a coordinated autonomic, endocrine, and behavioral response to the LPS challenge that was most pronounced 2 ho urs following injection. Specifically, Fos-like immunoreactivity was o bserved in key autonomic regulatory nuclear groups, including the insu lar and prelimbic cortices, paraventricular hypothalamic nucleus, para brachial nucleus, nucleus of the solitary tract, and the rostral and c audal levels of the ventrolateral medulla. In addition, a significant sustained elevation of Fos-like immunoreactivity was observed in a cel l group adjacent to the organum vasculosum of the lamina terminalis, w hich we termed the ventromedial preoptic area. This sustained elevatio n of Fos-like immunoreactivity coupled with the alterations in body te mperature elicited by LPS leads us to hypothesize that the ventromedia l preoptic area may be a key site for the initiation of fever during e ndotoxemia. (C) 1996 Wiley-Liss, Inc.