Augmented sensitivity to benzodiazepine in septic shock rats

Komatsubara, Takayuki; Kikuchi, Yuji; Saito, Shigeru

doi:10.1007/bf03011043

Cited by 9 publications

(3 citation statements)

References 31 publications

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“…105 Inflammatory mediators increase the insertion of GABA-A receptors in the neuron membrane, 106 and an increase in GABA-A receptor activity has been observed in septic rats. 107,108 Thus, it could be presumed that increased sensitivity to BZ occurs during systemic inflammation. In fact, GABA-A agonists worsen postoperative pain only in the presence of inflammation.…”

Section: 103mentioning

confidence: 99%

Septic encephalopathy: does inflammation drive the brain crazy?

Dal‐Pizzol

Tomasi

Ritter

2014

Rev. Bras. Psiquiatr.

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Sepsis and the multiorgan dysfunction syndrome are among the most common reasons for admission to an intensive care unit, and are a leading cause of death. During sepsis, the central nervous system (CNS) is one of the first organs affected, and this is clinically manifested as sepsis-associated encephalopathy (SAE). It is postulated that the common final pathway that leads to SAE symptoms is the deregulation of neurotransmitters, mainly acetylcholine. Thus, it is supposed that inflammation can affect neurotransmitters, which is associated with SAE development. In this review, we will cover the current evidence (or lack thereof) for the mechanisms by which systemic inflammation interferes with the metabolism of major CNS neurotransmitters, trying to explain how systemic inflammation drives the brain crazy.

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Section: 103mentioning

confidence: 99%

Septic encephalopathy: does inflammation drive the brain crazy?

Dal‐Pizzol

Tomasi

Ritter

2014

Rev. Bras. Psiquiatr.

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“…Other neurotransmitters may also play a role in the activity of the SNS. Studies have shown that the GABAergic tone in the forebrain of septic animals is enhanced (86)(87)(88), while others indicated that PVN activity can be inhibited by GABA A ergic neuronal inputs from the suprachiasmatic nuclei -an effect that can be reversed by the application of GABA-antagonists (84). Both systems (i.e., the excitatory glutamatergic and inhibitory GABAergic) have been extensively investigated and are known to regulate learning and memory in other regions of the brain, but their regulation of the sympathetic nerve activity remains elusive.…”

Section: Other Targets Of Sympathetic Modulation: Nmethyl-d-aspartatementioning

confidence: 99%

Sympathetic excitotoxicity in sepsis: pro-inflammatory priming of macrophages by norepinephrine

Miksa¹

2005

Front Biosci

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In the history of medicine, the interaction between mind and body has been repeatedly proposed. However, the influence of the nervous system on the immune regulation has, until now, drawn little attention. In this regard, the adrenergic system has been explored, and mainly catecholamine-mediated anti-inflammatory effects have been described. These inhibitory effects of epinephrine and norepinephrine were found to be mediated by beta2-adrenoceptors expressed on mononuclear cells. Recently, the role of the parasympathetic nervous system in the local anti-inflammatory reflex has been investigated. Stimulation of the vagus nerve decreases the pro-inflammatory response of macrophages via alpha7-cholinergic receptors. Thus, both the sympathetic and parasympathetic nervous systems are thought to work hand in hand in their anti-inflammatory responses. Here we discuss the deteriorating effects of the release of norepinephrine in sepsis. We have discovered that organ dysfunction in severe sepsis is mediated at least in part by an increase in pro-inflammatory cytokine release from Kupffer cells, which is caused by a priming via gut-derived norepinephrine. The sympathetic nervous system and gut-derived norepinephrine mediate the pro-inflammatory effects by activating alpha2A-adrenoceptor on Kupffer cells. In this review, we will focus on the differential function of the noradrenergic system on local and systemic inflammatory responses and the possibilities of the modulation of sympathetic outflow by centrally active inhibitors such as the novel peptide ghrelin or NMDA-receptor blockers. Furthermore, we will introduce the new concept of "sympathetic excitotoxicity in sepsis" characterized by the neurogenic priming of the systemic pro-inflammatory response.

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“…T he central nervous system is one of the first organs to be affected by sepsis, but the mechanism by which this dysfunction occurs in this condition has not been defined (1)(2)(3)(4)(5)(6)(7)(8). Several proposed mechanisms for the central nervous system dysfunction induced by sepsis include an alteration in the blood-brain barrier, amino acid disruption, and brain ischemia resulting from a global or regional reduction in the cerebral blood flow (6 -8).…”

mentioning

confidence: 98%

Cannabinoid antagonist AM 281 reduces mortality rate and neurologic dysfunction after cecal ligation and puncture in rats

Kikuchi

Hara

Kunimoto

et al. 2005

Critical Care Medicine

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Administration of AM 281 prevented the hemodynamic changes and development of neurologic dysfunction occurring in association with septic shock, and could decrease the mortality rate in experimentally induced septic shock in rats. Although further studies are necessary to determine whether endogenous cannabinoids cause septic encephalopathy in rats directly or via their effects on systemic hemodynamics, the beneficial effects of AM 281 on these rats might have significant therapeutic implications in cases of septic encephalopathy.

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Augmented sensitivity to benzodiazepine in septic shock rats

Cited by 9 publications

References 31 publications

Septic encephalopathy: does inflammation drive the brain crazy?

Septic encephalopathy: does inflammation drive the brain crazy?

Sympathetic excitotoxicity in sepsis: pro-inflammatory priming of macrophages by norepinephrine

Cannabinoid antagonist AM 281 reduces mortality rate and neurologic dysfunction after cecal ligation and puncture in rats

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