Jk. Elmquist et al., DISTRIBUTION OF FOS-LIKE IMMUNOREACTIVITY IN THE RAT-BRAIN FOLLOWING INTRAVENOUS LIPOPOLYSACCHARIDE ADMINISTRATION, Journal of comparative neurology, 371(1), 1996, pp. 85-103
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.