The role of the adrenergic system in septic encephalopathy

Davies, D.C.; Parmar, NK; Moss, R.E.; Tighe, D.; Bennett, E. D.

doi:10.1186/cc1247

Cited by 7 publications

(5 citation statements)

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“…The pathophysiology of sepsis-induced encephalopathy is incompletely understood [38]. Proposed mechanisms include microorganisms directly invading the central nervous system (CNS), microorganism-derived products entering the CNS [39, 40], metabolic abnormalities affecting CNS function [41, 42], disruption of blood-brain barrier [43–45], changes in neurotransmitter function synthesis and receptorial distribution [46], and impairment of brain circulation and auto-regulation [47, 48]. Thus, knowledge of histopathological changes in the CNS in the context of sepsis is of paramount importance to better understand the pathogenesis of sepsis-induced encephalopathy, determine its reversibility, and define potential preventive or therapeutic interventions.…”

Section: Methodsmentioning

confidence: 99%

Histopathological changes of organ dysfunction in sepsis

Garofalo

Lorente-Ros

Goncalvez

et al. 2019

ICMx

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Background Sepsis is a highly lethal disorder. Organ dysfunction in sepsis is not defined as a clinicopathological entity but rather by changes in clinical, physiological, or biochemical parameters. Pathogenesis and specific treatment of organ dysfunction in sepsis are unknown. The study of the histopathological correlate of organ dysfunction in sepsis will help understand its pathogenesis. Methods We searched in PubMed, EMBASE, and Scielo for original articles on kidney, brain, and liver dysfunction in human sepsis. A defined search strategy was designed, and pertinent articles that addressed the histopathological changes in sepsis were retrieved for review. Only studies considered relevant in the field were discussed. Results Studies on acute kidney injury (AKI) in sepsis reveal that acute tubular necrosis is less prevalent than other changes, indicating that kidney hypoperfusion is not the predominant pathogenetic mechanism of sepsis-induced AKI. Other more predominant histopathological changes are apoptosis, interstitial inflammation, and, to a lesser extent, thrombosis. Brain pathological findings include white matter hemorrhage and hypercoagulability, microabscess formation, central pontine myelinolysis, multifocal necrotizing leukoencephalopathy, metabolic changes, ischemic changes, and apoptosis. Liver pathology in sepsis includes steatosis, cholangiolitis and intrahepatic cholestasis, periportal inflammation, and apoptosis. There is no information on physiological or biochemical biomarkers of the histopathological findings. Conclusions Histopathological studies may provide important information for a better understanding of the pathogenesis of organ dysfunction in sepsis and for the design of potentially effective therapies. There is a lack of clinically available biomarkers for the identification of organ dysfunction as defined by the histological analysis.

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Section: Methodsmentioning

confidence: 99%

Histopathological changes of organ dysfunction in sepsis

Garofalo

Lorente-Ros

Goncalvez

et al. 2019

ICMx

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“…Such changes are likely to be due to inflammatory mediators, and in vitro studies have shown that interferon gamma causes increased permeability to human brain endothelial monolayers [40]. Additional factors associated with sepsis may also contribute to microvascular and blood brain barrier changes, such as stimulation of vascular alpha-1 adrenoceptors [21]. The effects of alteration in BBB and cerebral microvascular function include: impaired delivery of nutrients and removal of metabolic waste products, as well as increased access to the CNS of compounds whose presence is usually tightly controlled.…”

Section: Septic Encephalopathymentioning

confidence: 98%

Infection–associated encephalopathies—their investigation, diagnosis, and treatment

2006

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Reduced level of consciousness is a common clinical finding in acutely sick patients. In the majority of cases a cause for the encephalopathy is readily identifiable,whilst in a minority the aetiology is more difficult to ascertain. Frequently the onset of encephalopathy is associated with, or follows, infection. The mechanisms through which infection leads to encephalopathy are diverse. They range from direct microbial invasion of the brain or its supporting structures, to remote, infection-triggered mechanisms such as acute disseminated encephalomyelitis. Most common however, is the encephalopathy caused through a remote effect of systemic sepsis-septic encephalopathy. This article discusses the clinical presentation and underlying pathogeneses of the acute encephalopathies associated with infection, aiming to aid both their recognition and treatment.

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“…In the porcine caecal peritonitis model of systemic sepsis, intravenous treatment with the β 2 ‐adrenoceptor agonist dopexamine (0.6 mg kg −1 h −1 ) protected against sepsis‐induced perimicrovessel oedema (Fig. 1C) in the cerebral cortex (Davies et al. 2001).…”

Section: Blood–brain Barrier Breakdown and Oedema Formation In Septicmentioning

confidence: 99%

“…Methoxamine treatment also caused swelling of microvessel endothelial cells in both septic and non‐septic pigs. Conjoint dopexamine and methoxamine treatment did not prevent this endothelial cell swelling (Davies et al. 2001).…”

Section: Blood–brain Barrier Breakdown and Oedema Formation In Septicmentioning

confidence: 99%

Blood–brain barrier breakdown in septic encephalopathy and brain tumours*

2002

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Septic encephalopathy is associated with breakdown of the blood-brain barrier and cerebral oedema. These features are also common properties of brain tumours. Perimicrovessel oedema, disruption of associated astrocyte end feet and neuronal injury occur in a porcine model of acute septic encephalopathy. The adrenergic system has been implicated in the inflammatory response to sepsis and may play a role in controlling blood-brain barrier permeability, since the β 2 -adrenoceptor agonist dopexamine inhibits perimicrovessel oedema formation whereas the α 1 -adrenoceptor agonist methoxamine provokes it. Electron microscopy revealed tight junction opening in highgrade astrocytoma microvessels. Expression of the tight junction protein occludin is reduced in these microvessels and this reduction is inversely correlated with the degree of cerebral oedema. Normal astrocytes secrete factors that induce barrier properties in endothelial cells, whereas high-grade astrocytomas secrete vascular endothelial growth factor, which stimulates angiogenesis, down regulates occludin and increases endothelial cell permeability.The water channel protein aquaporin-4 is normally expressed in astrocyte foot processes around cerebral microvessels. Its expression is massively up-regulated in high-grade astrocytoma and around metastatic adenocarcinoma.There is a significant correlation between aquaporin-4 expression and the degree of cerebral oedema, but it is not clear whether increased aquaporin-4 expression enhances oedema formation or clearance. These results suggest that the pathophysiology of brain oedema is multifactorial, but that there may be common processes operating regardless of the aetiology.

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The role of the adrenergic system in septic encephalopathy

Cited by 7 publications

References 0 publications

Histopathological changes of organ dysfunction in sepsis

Histopathological changes of organ dysfunction in sepsis

Infection–associated encephalopathies—their investigation, diagnosis, and treatment

Blood–brain barrier breakdown in septic encephalopathy and brain tumours*

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