ANATOMIC PATTERNS OF FOS IMMUNOSTAINING IN RAT-BRAIN FOLLOWING SYSTEMIC ENDOTOXIN ADMINISTRATION

To identify brain neurons that participate in the acute phase response , rat brains were examined immunocytochemically for Fos protein follow ing the intravenous administration of bacterial endotoxin (lipopolysac charide, LPS). Two to three hours after the injection of LPS, 150 mu g /kg body weight, to adult male Long-Evens rats, a consistent anatomic pattern of Fos immunostained cell nuclei is seen. In the brain stem, p rominant Fos immunostaining is induced in tyrosine hydroxylase immunor eactive neurons of the caudal ventral-lateral medulla (the A1 cell gro up), in both tyrosine hydroxylase positive and negative neurons of nu. tractus solitarius, in the parabrachial nu., and in a few neurons of the locus ceruleus. In the hypothalamus, endotoxin induces Fos express ion in magnocellular neurons of the paraventricular and supraoptic nuc lei and internuclear cell groups. A higher percentage of oxytocin-immu noreactive cells is double labeled for Fos nuclear immunostaining than vasopressin-immunoreactive cells. A minority of somatostatin immunore active periventricular hypothalamic neurons are Fos positive. Other hy pothalamic nuclei that contain endotoxin-induced Fes nuclear immunosta ining include the parvocellular neurons of the paraventricular nu., th e dorsomedial and arcuate nuclei, the lateral hypothalamus, the dorsal hypothalamic area (zona incerta), and the median nucleus of the preop tic area. LPS induces numerous Fos-positive neurons in regions known t o respond to a variety of stressful stimuli; these regions include the preoptic area, bed nucleus of the stria terminalis, lateral septum, a nd the central and medial nuclei of the amygdala. Moreover, Fos nuclea r immunostaining is seen in neurons of circumventricular organs: the o rganum vasculosum of the lamina terminalis, the subfornical organ, and the area postrema. The maximum intensity of Fos nuclear immunostainin g occurs 2-3 h after endotoxin administration and declines thereafter. It is attenuated by pretreatment with indomethacin, 25 mg/kg body wei ght SC, or dexamethasone, 1 mg/kg IP. These observations are consisten t with the participation of a variety of brain neuronal systems in the acute phase response and elucidate the functional neuroanatomy of tha t response at the cellular level.