Induction by lipopolysaccharide of cyclooxygenase-2 mRNA in rat brain; its possible role in the febrile response

Cao, Chunyu; Matsumura, Kiyoshi; Watanabe, Yasuyoshi

doi:10.1016/0006-8993(95)00839-i

Cited by 238 publications

(146 citation statements)

References 35 publications

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“…[106][107][108] Systemic injection of LPS leads to the synthesis of iNOS and COX2 mRNA in cells of the BBB. 51,52,[109][110][111][112] Inhibition of these enzymes attenuates fever, activates c-Fos expression in the brainstem and hypothalamus and activates the HPA axis (upon systemic injection of LPS or IL-1␤). 79,[113][114][115][116][117] Injection of IL1Ra, prostaglandin or NO synthesis inhibitors into the OVLT attenuates IL-1␤ induced fever.…”

Section: Cytokine Cascadesmentioning

confidence: 99%

Cytokine signals propagate through the brain

et al. 2000

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Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF␣) are proinflammatory cytokines that are constitutively expressed in healthy, adult brain where they mediate normal neural functions such as sleep. They are neuromodulators expressed by and acting on neurons and glia. IL-1 and TNF␣ expression is upregulated in several important diseases/disorders. Upregulation of IL-1 and/or TNF␣ expression, elicited centrally or systemically, propagates through brain parenchyma following specific spatio-temporal patterns. We propose that cytokine signals propagate along neuronal projections and extracellular diffusion pathways by molecular cascades that need to be further elucidated. This elucidation is a prerequisite for better understanding of reciprocal interactions between nervous, endocrine and immune systems. Molecular Psychiatry (2000) 5, 604-615.

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Section: Cytokine Cascadesmentioning

confidence: 99%

Cytokine signals propagate through the brain

et al. 2000

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“…It was demonstrated that (i) LPS and pro-inflammatory cytokines can induce the expression of COX-2 mRNA (Cao et al, 1995;Vezzani and Granata, 2005), (ii) prostaglandins may have a role in the seizure threshold decreasing effect of LPS (Sayyah et al, 2003), (iii) PGE 2 has proconvulsant effect (Sayyah et al, 2003) and (iv) the T-type Ca 2+ channel evoked Ca 2+ current (which has a role in the genesis of absence seizure) decreasing effect of IND may diminish absence epileptic activity in WAG/Rij rats, GAERS rats and Long Evans rats (Depaulis and Van Luijtelaar, 2005;Polack and Charpier, 2006;Shin, 2006;Van Luijtelaar et al, 2000). Thus, indomethacin may exert its effect on absence epileptic activity (e.g.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide induced increase in seizure activity in two animal models of absence epilepsy WAG/Rij and GAERS rats and Long Evans rats

Kovács

Dobolyi

Juhász

et al. 2014

Brain Research Bulletin

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Absence epileptic rats a b s t r a c tWe showed previously that the number and time of spike-wave discharges (SWDs) were increased after intraperitoneal (i.p.) injection of lipopolysaccharide (LPS), an effect, which was completely abolished by cyclooxygenase-2 (COX-2) inhibitor indomethacin (IND) pretreatment in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. These and other results suggest that injection of LPS to genetically absence epileptic animals, such as WAG/Rij rats, may allow us to investigate relationships between absence epilepsy and LPS evoked neuroinflammation processes. However, LPS may evoke different effects on absence epileptic activity in various animal strains. Thus, to extend our previous results, we injected two doses of LPS (50 g/kg and 350 g/kg i.p.) alone and in combination with IND (10 mg/kg IND i.p. +50 g/kg LPS) into rats of two model animal strains (WAG/Rij rats; GAERS rats: Genetic Absence Epileptic Rats from Strasbourg) and into Long Evans rats. The effects of treatments on SWD number and SWD duration were examined. Both doses of LPS increased the SWD number and the total time of SWDs dose-dependently during the whole 4-h recording period, which was abolished by IND pretreatment in all three investigated strains. These results extend our previous results suggesting that our methods using LPS injection into freely moving absence epileptic rats is applicable not only in well-established animal models of absence epilepsy such as WAG/Rij rats and GAERS rats but also in Long Evans rats to investigate links between inflammation and absence epilepsy.

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“…The increase in CSF PGE 2 probably reflects the induction of COX-2 in the brain capillary endothelial cells where LPS or cytokines transiently enhance COX-2 mRNA and protein levels (31). COX-2 mRNA expression in brain capillary cells is enhanced as early as 1 h after peripheral LPS administration (100 g/kg ip) (6), which is compatible with the development of anorexia and other LPS-induced effects, such as fever and activation of the hypothalamic-pituitary-adrenal axis (35), which are also reported to be mediated by COX-2 and CNS PGs.…”

Section: Discussionmentioning

confidence: 99%

“…An alternative route of communication between the periphery and the CNS involves cytokine and LPS receptors on the surface of the cerebral endothelial cells of the brain-blood barrier (1,39) and subsequent mediators such as prostaglandins (PGs) (6). PGs are synthesized by cyclooxygenase (COX), an enzyme that exists in two different isoforms.…”

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confidence: 99%

A role for cyclooxygenase-2 in lipopolysaccharide-induced anorexia in rats

Lugarini¹,

Hrupka²,

Schwartz

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

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tion attenuated anorexia after lipopolysaccharide (LPS) administration, we tested the ability of resveratrol (2.5, 10, and 40 mg/kg) and NS-398 (2.5, 10, and 40 mg/kg), selective inhibitors of the two COX isoforms COX-1 and -2, respectively, to attenuate LPS (100 g/kg ip)-induced anorexia. NS-398 (10 and 40 mg/kg) administered with LPS at lights out attenuated LPS-induced anorexia, whereas resveratrol at all doses tested did not. Because prostaglandin (PG) E2 is considered the major metabolite synthesized by COX, we measured plasma and cerebrospinal fluid (CSF) PGE2 levels after LPS administration. LPS induced a time-dependent increase of PGE2 in CSF but not in plasma. NS-398 (5, 10, and 40 mg/kg) blocked the LPS-induced increase in CSF PGE2, whereas resveratrol (10 mg/kg) did not. These results support a role of COX-2 in mediating the anorectic response to peripheral LPS and point at PGE2 as a potential neuromodulator involved in this response.NS-398; resveratrol; prostaglandin E2; food intake; fever LIPOPOLYSACCHARIDE (LPS) and proinflammatory cytokines [e.g., interleukin (IL)-1␤, IL-6, and tumor necrosis factor-␣] induce anorexia and fever (32), two phenomena partly independent of each other. Brain areas involved in feeding and body temperature regulation are activated (5, 40) after peripheral administration of LPS and cytokines. This can be accomplished through neural and/or humoral communications with the central nervous system (CNS). Vagal afferents have been implicated in some of the behavioral effects induced by peripheral LPS or cytokines (3, 16). In our hands, however, subdiaphragmatic vagal deafferentation, alone or in combination with celiac-superior mesenteric ganglionectomy, did not attenuate the anorectic response to peripheral LPS, muramyl dipeptide, and IL-1␤ (33). An alternative route of communication between the periphery and the CNS involves cytokine and LPS receptors on the surface of the cerebral endothelial cells of the brain-blood barrier (1, 39) and subsequent mediators such as prostaglandins (PGs) (6). PGs are synthesized by cyclooxygenase (COX), an enzyme that exists in two different isoforms. COX-1 is constitutively expressed in many tissues, mainly outside the brain, and its levels are relatively insensitive to inflammatory stimulation. COX-1 is scarcely expressed in capillary endothelial and perivascular glial cells (13). COX-2, on the other hand, is constitutively expressed at low levels in neurons of the cortex, hippocampus, and amygdala, but not in the cells of the cerebral vasculature (34). COX-2 is strongly induced in brain vasculature, however, by LPS and IL-1␤ (12,22,34). LPS or cytokines (31) transiently enhance COX-2 mRNA and protein levels via activation of nuclear factor-B (2, 23).In our hands, nonselective pharmacological inhibition of COX by administration of indomethacin or paracetamol attenuated the pyretic and hypophagic effects of peripheral 27). Selective inhibition of COX-2 blocks LPS-induced fever (7). Use of selective inhibitors for COX-1 and -2 could not establ...

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Induction by lipopolysaccharide of cyclooxygenase-2 mRNA in rat brain; its possible role in the febrile response

Cited by 238 publications

References 35 publications

Cytokine signals propagate through the brain

Cytokine signals propagate through the brain

Lipopolysaccharide induced increase in seizure activity in two animal models of absence epilepsy WAG/Rij and GAERS rats and Long Evans rats

A role for cyclooxygenase-2 in lipopolysaccharide-induced anorexia in rats

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