Lipopolysaccharide-induced production of tumor necrosis factor activity in rats with and without risk factors for stroke

Hallenbeck, John M.; Dutka, A. J.; Vogel, Stefanie N.; Heldman, Eliahu; Doron, David A.; Feuerstein, Giora

doi:10.1016/0006-8993(91)91083-d

Cited by 47 publications

(18 citation statements)

References 30 publications

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“…4 In the present study the previous findings were confirmed in SHR. Moreover, hypertensive rats produced more TNF-a in the cerebrospinal fluid in response to lipopolysaccharide than normotensive rats.…”

Section: Discussionsupporting

confidence: 87%

Release of proinflammatory and prothrombotic mediators in the brain and peripheral circulation in spontaneously hypertensive and normotensive Wistar-Kyoto rats.

Sirén

Heldman

Doron

et al. 1992

Stroke

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Background and Purpose:We reported previously that stroke risk factors prepared the brain stem for the development of ischemia and hemorrhage and induced the production of tumor necrosis factor following an intrathecal injection of lipopolysaccharide, a prototypic monocyte-activating stimulus. This study evaluates whether blood or brain cells of hypertensive rats produce more proinflammatory and prothrombotic mediators than do blood or brain cells of normotensive rats.Methods: Levels of tumor necrosis factor, platelet-activating factor, 6-ketoprostaglandin F la , and thromboxane B 2 in the cerebrospinal fluid and blood of spontaneously hypertensive and normotensive Wistar-Kyoto rats were monitored before and after a challenge with lipopolysaccharide.Results: Little or no activity from these mediators was found in the cerebrospinal fluid or blood of saline-injected control animals. Intravenous administration of lipopolysaccharide (0.001, 0.1, and 1.8 nig/kg) produced dose-dependent increases in blood levels of all mediators in hypertensive rats. In normotensive rats the levels were less than in hypertensive rats and were not clearly dose-related. When lipopolysaccharide was injected intracerebroventricularly, more tumor necrosis factor was measured in the cerebrospinal fluid than in the blood, suggesting local synthesis of this cytokine. Levels of tumor necrosis factor and platelet-activating factor in the cerebrospinal fluid were higher in hypertensive than in normotensive rats. The thromboxane A 2 /prostacyclin ratio was not altered significantly between the two rat strains.Conclusions: It is suggested that the higher incidence of brain stem ischemia and hemorrhage after the intrathecal injection of lipopolysaccharide in hypertensive rats than in normotensive rats might be related to the higher levels of the two cytotoxic factors tumor necrosis factor and platelet-activating factor produced in response to such challenge.

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Section: Discussionsupporting

confidence: 87%

Release of proinflammatory and prothrombotic mediators in the brain and peripheral circulation in spontaneously hypertensive and normotensive Wistar-Kyoto rats.

Sirén

Heldman

Doron

et al. 1992

Stroke

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“…Although differences between the in vitro responsiveness of the SHR EC and WKY or SD EC cultures were observed only at suboptimal concentrations of cytokines, more differences could exist in vivo, where endothelium is subjected to blood flow/shear stress, factors related to hypertension and various agents including cytokines which may be rapidly washed away. Such in vivo differences are indicated by observations that LPS induces greater increases in plasma Ievels of TNFa in SHR than in WKY rats (35). Additional studies regarding the influence of hypertension, as well as other potential risk factors for stroke, on expression of adhesion molecules by endothelium may provide insight toward defining a mechanism by which these factors contribute to the initiation of vascular injury.…”

Section: Discussionmentioning

confidence: 99%

Adhesion Molecules on Normotensive and Hypertensive Rat Brain Endothelial Cells

McCarron

Wang

Sirén

et al. 1994

Experimental Biology and Medicine

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Abstract. The intercellular adhesion of circulating leukocytes to vascular endothellum ls a prerequisite for leukocyte emigration from the blood to extravascular tlssues. Thls process ls facllltated by adheslon molecules on the surfaces of both the vascular endothelial cells and the leukocytes. The experiments presented here demonstrate for the firsttimethat the leukocyte adheslon receptor, lntercellular adhesion molecule-1, ls constitutlvely expressed on cultured cerebromlcrovascular endothellal cell llnes derlved from both spontaneously hypertensive (SHR) rats and normotenslve WlstarKyoto (WKY) rats. Both cultures contalned simllar numbers of cells constltutlvely expressing thls adheslon molecule (31.4% and 29.6%, respectlvely). Adheslon molecule expresslon was up-regulated by lnterleukln-1 ß, tumor necrosis factor-a, lnterferon-y and lipopolysaccharide in a dose-and tlme-dependent manner. Both cultures exhiblted similar maximum Ieveis of adhesion molecule up-regulation to optimal concentratlons of all three cytokines. However, SHR endothelial cells were moresensitive to all three cytokines; slgnificantly higher Ieveis of lntercellular adhesion molecule-1 expresslon were seen on SHR as opposed to WKY endothellal cells cultured with sub-optimal cytoklne concentratlons. lt was also observed that lipopolysaccharide up-regulated intercellular adhesion molecule-1 expression on SHR endothellal cells to a greater extent than on WKY endothellal cells.The findings that intercellular adheslon molecule-1 can be up-regulated to a greater degree on SHR endothellal cells may have lmportant lmplications for ln vlvo perlvascular leukocyte accumulatlon under hypertensive condltlons. These Observations lndlcate a possible mechanism by which hypertension may predlspose to the development of dlsorders such as atherosclerosis and stroke. [P.S.E.B.M. 1994, Vol205] T he adhesion of leukocytes to vascular endothelial cells (EC) is an initial, critical step required for their emigration from the blood stream to extravascular tissues (1-3). The adhesion event is facilitated by a variety of adhesion molecules present on the surfaces of EC (e.g., intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1,

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“…6 Compared with WKY, mature SHR have significantly elevated neutrophil, monocyte, and lymphocyte counts in their blood, 7 with an abnormal degree of activation of these cells, and they produce higher levels of TNF and platelet-activating factor in cerebrospinal fluid after intravenous lipopolysaccharide administration. 8 Neutrophils have been proposed to contribute to ischemic injury, migrating to the site via a process of rolling and tethering to the blood vessel wall through the expression of adhesion molecules on their surface and on the endothelium of blood vessels.…”

mentioning

confidence: 99%

Characterization of the Microglial Response to Cerebral Ischemia in the Stroke-Prone Spontaneously Hypertensive Rat

et al. 2001

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Lipopolysaccharide-induced production of tumor necrosis factor activity in rats with and without risk factors for stroke

Cited by 47 publications

References 30 publications

Release of proinflammatory and prothrombotic mediators in the brain and peripheral circulation in spontaneously hypertensive and normotensive Wistar-Kyoto rats.

Release of proinflammatory and prothrombotic mediators in the brain and peripheral circulation in spontaneously hypertensive and normotensive Wistar-Kyoto rats.

Adhesion Molecules on Normotensive and Hypertensive Rat Brain Endothelial Cells

Characterization of the Microglial Response to Cerebral Ischemia in the Stroke-Prone Spontaneously Hypertensive Rat

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