Neural and biochemical mediators of endotoxin and stress-induced c-fos expression in the rat brain

Wan, Weihua; Wetmore, Lisa; Sorensen, Craig M.; Greenberg, Arnold H.; Nance, Dwight M.

doi:10.1016/0361-9230(94)90179-1

Cited by 299 publications

(161 citation statements)

References 56 publications

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“…Vagal sensory input from the abdomen implicated in the central neural (Wan, et al, 1994), hyperthermic , and hormonal (Fleshner, et al, 1995;Gaykema, et al, 1995;Kapcala, et al, 1996) responses to inflammatory stimuli may have contributed to this response as may the action of circulating mediators on the area postrema (Cunningham et al, 1994). However, Fos appeared in this circumventricular organ only in the rats with the most intense dorsomedullary responses as reported previously during acute inflammation Ericsson, et al, 1994).…”

Section: Discussionsupporting

confidence: 54%

“…This surgical model mirrors the clinical course of sepsis and recreates a sequence of events that differs from that after a lethal dose of endotoxin in both time course and the release and distribution of inflammatory mediators (Mathiak, et al, 2000;Wichterman, et al, 1980). The presence of peritonitis and a surgically induced cecal abscess in the model may constitute a sustained stimulus to visceral sensory pathways that respond to tissue inflammation (Fleshner et al, 1995;Gaykema, et al, 1995;Kapcala et al, 1996;Wan, et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

“…The administration of bacterial endotoxin has gained wide use as a systemic inflammatory stimulus (Beishuizen and Thijs, 2003;Carlson et al, 1997;Gaykema et al, 1995;Wan et al, 1994;Watkins et al, 1994), but the utility of endotoxin administration as an experimental model of sepsis has been questioned (Mathiak et al, 2000;Wichterman et al, 1980). The central neural responses to acute doses of endotoxin Wan, et al, 1994) or inflammatory cytokines (Chan et al, 1993;Crane et al, 2003;Ericsson et al, 1994;Xu et al, 1999) have been well described and are likely to be present in sepsis but may comprise only a subset of the complete response to prolonged systemic infection.…”

Section: Introductionmentioning

confidence: 99%

“…The central neural responses to acute doses of endotoxin Wan, et al, 1994) or inflammatory cytokines (Chan et al, 1993;Crane et al, 2003;Ericsson et al, 1994;Xu et al, 1999) have been well described and are likely to be present in sepsis but may comprise only a subset of the complete response to prolonged systemic infection. The central modulation of the immune system and of metabolism is likely to affect the clinical course of sepsis significantly.…”

Section: Introductionmentioning

confidence: 99%

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Central neural distribution of immunoreactive Fos and CRH in relation to plasma ACTH and corticosterone during sepsis in the rat

Carlson

Chiu

Fiedler

et al. 2007

Experimental Neurology

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Although brain pathways activated by sepsis may respond acutely to endotoxin administration, the long-term central response to sepsis is not known. We prepared male rats for hormonal sampling at the circadian nadir (AM) and peak (PM) after cecal ligation and puncture (CLP) or sham surgery. Diurnal variation of corticosterone was present on postoperative day (D) 3 and D4 after sham surgery but not after CLP. CLP increased Fos immunostaining in the nucleus of tractus solitarius (NTS), ventrolateral medulla, medullary raphe, parabrachial nucleus, hypothalamus, amygdala, bed nucleus of stria terminalis, and preoptic region. Fos responses were generally greatest on D1 but persisted to the AM of D4. The number of Fos-positive cell nuclei in the NTS on D3 and D4 did not differ but had greater variance on D3 than on D4 (P < 0.01) with a divergent response in the PM of D3 that was correlated with plasma ACTH (r = 0.927, P<0.01) but not with corticosterone. CLP increased CRH-staining intensity in the hypothalamic paraventricular neurons uniformly from D1 through D4 (P<0.01). Similar to Fos in NTS, this response was correlated with plasma ACTH (r = 0.738, P<0.05) and adrenal size (r = 0.730, P<0.05) in the PM of D3. Neuronal CRH became detectable after CLP in specific medullary areas on D1 and in the preoptic region on D3 and D4. Thus, the suppression of circadian variation by CLP was associated with central neural responses that increased in relation to plasma ACTH without apparent influence on the release of corticosterone.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Central neural distribution of immunoreactive Fos and CRH in relation to plasma ACTH and corticosterone during sepsis in the rat

Carlson

Chiu

Fiedler

et al. 2007

Experimental Neurology

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“…Initially, it was demonstrated that a subdiaphragmatic vagotomy prevented the cerebral Fos response to ip LPS [129]. Subsequently, several groups demonstrated that vagal lesions could prevent the CNS effects of ip IL-1 or LPS on behavior [130,131].…”

Section: Mechanisms Of the Neurochemical Effects Of Cytokinesmentioning

confidence: 99%

Effects of cytokines and infections on brain neurochemistry

Dunn

2006

Clinical Neuroscience Research

281

169

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Administration of cytokines to animals can elicit many effects on the brain, particularly neuroendocrine and behavioral effects. Cytokine administration also alters neurotransmission, which may underlie these effects. The most well studied effect is the activation of the hypothalamopituitary-adrenocortical (HPA) axis, especially that by interleukin-1 (IL-1). Peripheral and central administration of IL-1 also induces norepinephrine (NE) release in the brain, most markedly in the hypothalamus. Small changes in brain dopamine (DA) are occasionally observed, but these effects are not regionally selective. IL-1 also increases brain concentrations of tryptophan, and the metabolism of serotonin (5-HT) throughout the brain in a regionally nonselective manner. Increases of tryptophan and 5-HT, but not NE, are also elicited by IL-6, which also activates the HPA axis, although it is much less potent in these respects than IL-1. IL-2 has modest effects on DA, NE and 5-HT. Like IL-6, tumor necrosis factor-α (TNFα) activates the HPA axis, but affects NE and tryptophan only at high doses. The interferons (IFN's) induce fever and HPA axis activation in man, but such effects are weak or absent in rodents. The reported effects of IFN's on brain catecholamines and serotonin have been very varied. However, interferon-γ, and to a lesser extent, interferon-α, have profound effects on the catabolism of tryptophan, effectively reducing its concentration in plasma, and may thus limit brain 5-HT synthesis.Administration of endotoxin (LPS) elicits responses similar to those of IL-1. Bacterial and viral infections induce HPA activation, and also increase brain NE and 5-HT metabolism and brain tryptophan. Typically, there is also behavioral depression. These effects are strikingly similar to those of IL-1, suggesting that IL-1 secretion, which accompanies many infections, may mediate these responses. Studies with IL-1 antagonists, support this possibility, although in most cases the antagonism is incomplete, suggesting the existence of multiple mechanisms. Because LPS is known to stimulate the secretion of IL-1, IL-6 and TNFα, it seems likely that these cytokines mediate at least some of the responses, but studies with antagonists indicate that there are multiple mechanisms. The neurochemical responses to cytokines are likely to underlie the endocrine and behavioral responses. The NE response to IL-1 appears to be instrumental in the HPA activation, but other mechanisms exist. Neither the noradrenergic nor the serotonergic systems appear to be involved in the major behavioral responses. The significance of the serotonin response is unknown.

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Distribution of fos-like immunoreactivity in the rat brain following intravenous lipopolysaccharide administration

et al. 1996

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The central nervous system, particularly the hypothalamus, is intimately involved in the coordination of various aspects of the inflammatory response, including the generation of fever. We used intravenous injections of bacterial cell wall lipopolysaccharide (LPS; 5 or 125 micrograms/kg) to stimulate the acute phase response and mapped the resultant distribution of Fos-like immunoreactivity in the rat brain. In addition, we compared the patterns of Fos distribution with the thermoregulatory responses elicited by the LPS. Administration of LPS resulted in a dose- 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 hours following injection. Specifically, Fos-like immunoreactivity was observed in key autonomic regulatory nuclear groups, including the insular and prelimbic cortices, paraventricular hypothalamic nucleus, parabrachial nucleus, nucleus of the solitary tract, and the rostral and caudal levels of the ventrolateral medulla. In addition, a significant sustained elevation of Fos-like immunoreactivity was observed in a cell group adjacent to the organum vasculosum of the lamina terminalis, which we termed the ventromedial preoptic area. This sustained elevation of Fos-like immunoreactivity coupled with the alterations in body temperature elicited by LPS leads us to hypothesize that the ventromedial preoptic area may be a key site for the initiation of fever during endotoxemia.

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Neural and biochemical mediators of endotoxin and stress-induced c-fos expression in the rat brain

Cited by 299 publications

References 56 publications

Central neural distribution of immunoreactive Fos and CRH in relation to plasma ACTH and corticosterone during sepsis in the rat

Central neural distribution of immunoreactive Fos and CRH in relation to plasma ACTH and corticosterone during sepsis in the rat

Effects of cytokines and infections on brain neurochemistry

Distribution of fos-like immunoreactivity in the rat brain following intravenous lipopolysaccharide administration

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