Endotoxin-induced gene expression differences in the brain and effects of iNOS inhibition and norepinephrine

Wolff, S.; Klatt, Sabine; Wolff, Jens C.; Wilhelm, Jochen; Fink, Ludger; Kaps, Manfred; Rosengarten, Bernhard

doi:10.1007/s00134-009-1394-7

Cited by 22 publications

(18 citation statements)

References 36 publications

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“…We did not find a significant effect of NE on the cytokine level and also did not find significant effects on the gene expression levels of chemokines [37]. Our data are therefore in line with others who found epinephrine but not NE to modulate cytokine levels in a porcine model of endotoxic shock [38].…”

Section: Discussionsupporting

confidence: 89%

Effects of inducible nitric oxide synthase inhibition or norepinephrine on the neurovascular coupling in an endotoxic rat shock model

et al. 2009

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Section: Discussionsupporting

confidence: 89%

Effects of inducible nitric oxide synthase inhibition or norepinephrine on the neurovascular coupling in an endotoxic rat shock model

et al. 2009

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“…We speculate that these protective effects might be linked to the anti-inflammatory property of VNS. Conversely, it was shown that increased endotoxin doses resulted in a more severe uncoupling of the NVC relative to the severity of the inflammatory responses [12]. …”

Section: Discussionmentioning

confidence: 99%

Effects of anti-inflammatory vagus nerve stimulation on the cerebral microcirculation in endotoxinemic rats

Mihaylova

Killian

Mayer

et al. 2012

J Neuroinflammation

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BackgroundIn sepsis syndromes the severity of the inflammation triggers microvascular dysfunction and early organ failure. We studied the effects of anti-inflammatory vagus nerve stimulation on the cerebral microcirculatory integrity in an endotoxinemic rat model.MethodsIn both control and endotoxinemic (5 mg/kg lipopolysaccharide i.v.) rats, the effect of cervical bilateral vagotomy with or without left-sided distal vagus nerve stimulation were compared to non-vagotomized, nonstimulated group (sham). Neurovascular coupling was analyzed by electrical forepaw stimulation, EEG, and cortical laser-Doppler flow recording. Resting cerebral blood flow, evoked potentials and hemodynamic responses, were obtained over a period of 4.5 hours. Regulation of the nitric oxide system (iNOS expression and nitrite/nitrate measurements), cytokines (IFN-γ, TNF-α, IL-6, IL-10), hypoxic and apoptosis signaling molecules (HIF-2α, Bax) were measured at the end of experiments.ResultsIn endotoxinemic rats, vagus nerve stimulation tended to increase anti-inflammatory cytokine levels and resulted in a stabile hemodynamic response (28 ± 13%; versus baseline). Vagotomized animals incurred a pro-inflammatory response (7 ± 4%; P < 0.0001 versus baseline) and produced more HIF-2α than vagotomized vagus nerve stimulated (VNS) animals. Evoked potential amplitudes were stabilized in VNS (15 ± 7 μV; n.s. versus baseline) as compared to vagotomised rats (8 ± 5 μV; P < 0.001 versus baseline). However, no effects were observed on apoptosis markers or nitric oxide levels.ConclusionsVagus nerve stimulation in endotoxinemic rats had a positive effect on neurovascular coupling and stabilized evoked potentials.

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“…The hippocampi were selected for analysis because it has been shown that this particular brain region displays the most robust induction of cytokine expression upon systemic inflammatory challenge by LPS [65], [66] We extracted total RNA using the TRI® reagent (Sigma) according to the manufacturer’s protocol. Briefly, the frozen tissue was thawed and mechanically dissociated in 1 ml TRI reagent.…”

Section: Methodsmentioning

confidence: 99%

Molecular Hydrogen Reduces LPS-Induced Neuroinflammation and Promotes Recovery from Sickness Behaviour in Mice

et al. 2012

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Molecular hydrogen has been shown to have neuroprotective effects in mouse models of acute neurodegeneration. The effect was suggested to be mediated by its free-radical scavenger properties. However, it has been shown recently that molecular hydrogen alters gene expression and protein phosphorylation. The aim of this study was to test whether chronic ad libitum consumption of molecular hydrogen-enriched electrochemically reduced water (H-ERW) improves the outcome of lipopolysaccharide (LPS)-induced neuroinflammation. Seven days after the initiation of H-ERW treatment, C57Bl/6 mice received a single injection of LPS (0.33 mg/kg i.p.) or an equivalent volume of vehicle. The LPS-induced sickness behaviour was assessed 2 h after the injection, and recovery was assessed by monitoring the spontaneous locomotor activity in the homecage for 72 h after the administration of LPS. The mice were killed in the acute or recovery phase, and the expression of pro- and antiinflammatory cytokines in the hippocampus was assessed by real-time PCR. We found that molecular hydrogen reduces the LPS-induced sickness behaviour and promotes recovery. These effects are associated with a shift towards anti-inflammatory gene expression profile at baseline (downregulation of TNF- α and upregulation of IL-10). In addition, molecular hydrogen increases the amplitude, but shortens the duration and promotes the extinction of neuroinflammation. Consistently, molecular hydrogen modulates the activation and gene expression in a similar fashion in immortalized murine microglia (BV-2 cell line), suggesting that the effects observed in vivo may involve the modulation of microglial activation. Taken together, our data point to the regulation of cytokine expression being an additional critical mechanism underlying the beneficial effects of molecular hydrogen.

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Endotoxin-induced gene expression differences in the brain and effects of iNOS inhibition and norepinephrine

Cited by 22 publications

References 36 publications

Effects of inducible nitric oxide synthase inhibition or norepinephrine on the neurovascular coupling in an endotoxic rat shock model

Effects of inducible nitric oxide synthase inhibition or norepinephrine on the neurovascular coupling in an endotoxic rat shock model

Effects of anti-inflammatory vagus nerve stimulation on the cerebral microcirculation in endotoxinemic rats

Molecular Hydrogen Reduces LPS-Induced Neuroinflammation and Promotes Recovery from Sickness Behaviour in Mice

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