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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

On one side, brain dysfunction is a poorly explored complication of sepsis. On the other side, brain dysfunction may actively contribute to the pathogenesis of sepsis. The current review aimed at summarizing the current knowledge about the reciprocal interaction between the immune and central nervous systems during sepsis. The immune-brain cross talk takes part in circumventricular organs that, being free from blood-brain-barrier, interface between brain and bloodstream, in autonomic nuclei including the vagus nerve, and finally through the damaged endothelium. Recent observations have confirmed that sepsis is associated with excessive brain inflammation and neuronal apoptosis which clinical relevance remains to be explored. In parallel, damage within autonomic nervous and neuroendocrine systems may contribute to sepsis induced organ dysfunction.
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PMID:Science review: The brain in sepsis--culprit and victim. 1569 82

A diffuse cerebral dysfunction is often present in sepsis and may ensues even before signs of other organ failure. It is better defined as ''Sepsis Associated Encephalopathy'' (SAE), in order to stress the absence of direct infection of the central nervous system. The main sign of SAE is an altered mental status. Electroencephalography is the more sensitive diagnostic test, and allows the grading of the severity of cerebral dysfunction that is related to outcome. SAE is potentially reversible, but it always worsens the prognosis. Pathophysiology of SAE is not still completely understood, and it is probably multifactorial. Indeed, brain dysfunction in sepsis may be related to action of micro-organisms toxins, to the effects of inflammatory mediators, to metabolic alterations and to abnormalities in cerebral circulation. At this moment a specific treatment for SAE does not exist and outcome relies upon prompt and appropriate treatment of sepsis as a whole.
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PMID:Sepsis associated encephalopathy. 1571 5

Sepsis causes brain dysfunction. Because neurotransmission requires high ascorbate and low dehydroascorbic acid (DHAA) concentrations in brain extracellular fluid, the effect of septic insult on ascorbate recycling (i.e., uptake and reduction of DHAA) and export was investigated in primary rat and mouse astrocytes. DHAA raised intracellular ascorbate to physiological levels but extracellular ascorbate only slightly. Septic insult by lipopolysaccharide and interferon-gamma increased ascorbate recycling in astrocytes permeabilized with saponin but decreased it in those with intact plasma membrane. The decrease was due to inhibition of the glucose transporter (GLUT1) that translocates DHAA because septic insult slowed uptake of the nonmetabolizable GLUT1 substrate 3-O-methylglucose. Septic insult also abolished stimulation by glutamate of ascorbate export. Specific nitric oxide synthase (NOS) inhibitors and nNOS and iNOS deficiency failed to alter the effects of septic insult. Inhibitors of NADPH oxidase generally did not protect against septic insult, because only one of those tested (diphenylene iodonium) increased GLUT1 activity and ascorbate recycling. We conclude that astrocytes take up DHAA and use it to synthesize ascorbate that is exported in response to glutamate. This mechanism may provide the antioxidant on demand to neurons under normal conditions, but it is attenuated after septic insult.
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PMID:Sepsis inhibits recycling and glutamate-stimulated export of ascorbate by astrocytes. 1619 26

Sepsis-associated encephalopathy (SAE) is a frequent but poorly understood neurological complication in sepsis that negatively influences survival. Here we present clinical and experimental evidence that this brain dysfunction may be related to altered neurotransmission produced by inflammatory mediators. Compared with septic patients, SAE patients had higher interleukin-1beta (IL-1beta) plasma levels; interestingly, these levels decreased once the encephalopathy was resolved. A putative IL-1beta effect on type A gamma-aminobutyric acid receptors (GABA(A)Rs), which mediate fast synaptic transmission in most cerebral inhibitory synapses in mammals, was investigated in cultured hippocampal neurons and in Xenopus oocytes expressing native or foreign rat brain GABA(A)Rs, respectively. Confocal images in both cell types revealed that IL-1beta increases recruitment of GABA(A)Rs to the cell surface. Moreover, brief applications of IL-1beta to voltage-clamped oocytes yielded a delayed potentiation of the GABA-elicited chloride currents (I(GABA)); this effect was suppressed by IL-1ra, the natural IL-1 receptor (IL-1RI) antagonist. Western blot analysis combined with I(GABA) recording and confocal images of GABA(A) Rs in oocytes showed that IL-1beta stimulates the IL-1RI-dependent phosphatidylinositol 3-kinase activation and the consequent facilitation of phospho-Akt-mediated insertion of GABA(A)Rs into the cell surface. The interruption of this signaling pathway by specific phosphatidylinositol 3-kinase or Akt inhibitors suppresses the cytokine-mediated effects on GABA(A)R, whereas activation of the conditionally active form of Akt1 (myr-Akt1.ER*) with 4-hydroxytamoxifen reproduces the effects. These findings point to a previously unrecognized signaling pathway that connects IL-1beta with increased "GABAergic tone." We propose that through this mechanism IL-1beta might alter synaptic strength at central GABAergic synapses and so contribute to the cognitive dysfunction observed in SAE.
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PMID:Interleukin-1beta enhances GABAA receptor cell-surface expression by a phosphatidylinositol 3-kinase/Akt pathway: relevance to sepsis-associated encephalopathy. 1656 7

Sepsis-associated encephalopathy is a global cerebral dysfunction induced by the systemic response to inflammation and infection, without a liver or renal injury. Alteration of consciousness, from confusion to coma, is the main clinical symptom. This encephalopathy is associated with an increase in mortality due to sepsis. Its physiopathology is unknown. There is frequently an increased permeability of the blood-brain barrier, which might explain a role of endotoxins on cerebral metabolism. Changes in neurotransmitter release or concentrations (norepinephrine, serotonin, dopamine, GABA) have been reported. There is not any specific treatment of septic encephalopathy. In most cases, this syndrome is rapidly reversible after the treatment of sepsis.
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PMID:[Brain injury during severe sepsis]. 1669 Feb 46

Beyond the cerebral impact of cardiac arrest, recent research indicates a high prevalence of neurological disturbances such as delirium and coma among patients admitted to the intensive care unit (ICU). These disturbances, grouped here under the term "encephalopathy," may be overlooked while attention is devoted to reversing life-threatening imbalances in cardiac and pulmonary function. Nevertheless, there is ample evidence that encephalopathy is an independent predictor of mortality. Factors associated with encephalopathy include primary cerebral disorders such as stroke, trauma, and meningitis, or systemic derangements including sepsis, organ failure, and exposure to pharmacological agents and toxins. Although encephalopathy may resolve with treatment of the underlying disorder, there is mounting evidence that cerebral dysfunction persists beyond the acute phase of critical illness. ICU survivors often suffer chronic impairments in cognitive ability, suggesting occult brain injury. The pathogenesis and natural history of encephalopathy, still poorly understood, need further clarification to spur the development of effective preventive and therapeutic interventions.
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PMID:The spectrum of encephalopathy in critical illness. 1696 45

Sepsis is often complicated by encephalopathy, neuroendocrine dysfunction and cardiovascular autonomic failure. The cause of septic brain dysfunction is not fully understood. The aim of the present study is to explore whether septic brain dysfunction in a common septic model in the rat correlates with abnormalities either of local cerebral blood flow (LCBF) of defined brain areas or of whole brain blood flow (CBF). 45 male Wistar rats (320+/-13 g) were randomly assigned to a sepsis group (31 rats, cecal ligature and puncture, CLP) or a control group (14 rats, sham operation). Of these 45 rats, 16 rats were used for blood analysis; the remaining 29 rats were used for CBF/LCBF measurements. LCBF measurements were performed 24h after initial surgery using quantitative autoradiography with 4-iodo[N-methyl-(14)C]antipyrine, which allows to analyze CBF on a regional/local and global basis. In 42 different brain regions bilateral optical density measurements were performed. Septic rats (vs. control) presented tachycardia (507+/-37 vs. 452+/-44 min(-1), P<0.05), leukocytopenia (2.96+/-2.37 vs. 8.83+/-2.9710(9) x L(-1), P<0.05), hypocapnia (29.3+/-4.6 vs. 36.4+/-3.9 mmHg, P<0.05), and higher serum lactate concentrations (5.7+/-3.9 vs. 2.2+/-2.0 mmol x L(-1), P<0.05). LCBF of all 42 areas, as well as, CBF (116+/-59 vs. 115+/-52 m x 100 g(-1)min(-1), n.s.) did not differ. The results showed that severe sepsis (mortality rate of 43 %) did not induce alterations in mean CBF and LCBF. It is concluded that brain dysfunction is not reflected in changes of CBF during severe sepsis.
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PMID:Local cerebral blood flow is preserved in sepsis. 1731 43

The cause of brain dysfunction during sepsis and septic encephalopathy is still under ongoing research. Sepsis induced changes in cerebral protein expression may play a significant role in the understanding of septic encephalopathy. The aim of the present study was to explore cerebral proteome alterations in septic rats. Fifty-six male Wistar rats were randomly assigned to a sepsis group (coecal ligature and puncture, CLP) or a control group (sham). Surviving rats were killed 24 or 48 hours after surgery and whole-brain lysates were used for two-dimensional gel electrophoresis and subsequent protein identification. Differentially expressed proteins were identified by mass spectrometry. Using the Ingenuity Pathways Analysis (IPA) tool, the relationship and interaction between the identified proteins was analyzed. Mortality was 53 % in septic rats. No rat of the control group was lost. More than 1,100 spots per gel were discriminated of which 29 different proteins were significantly (2-fold, P<0.01) changed: 24 proteins down-regulated after 24 hours; two proteins up-regulated and three down-regulated after 48 hours. IPA identified 11 of 35 differentially regulated proteins allocating them to an existing inflammatory pathway. In the analysis of septic rat brains, multiple differentially expressed proteins associated with metabolism, signaling, and cell stress can be identified via proteome analysis, that may help to understand the development of septic encephalopathy.
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PMID:Alterations in cerebral metabolomics and proteomic expression during sepsis. 1804 54

Investigations on the relationship between sepsis, brain dysfunction, and cerebral perfusion are methodologically very difficult to perform. It is important to interpret the results of such studies in view of our limited ability to diagnose and quantify brain dysfunction and to consider our limited understanding of the mechanisms that lead to or are associated with brain dysfunction in sepsis.
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PMID:Brain dysfunction in sepsis: what can we learn from cerebral perfusion studies? 1804 92

Delirium, or acute brain dysfunction, is a life-threatening global disturbance in cognitive functioning that frequently manifests in critically ill patients. This review examines the current status of knowledge regarding the pathophysiology of delirium in the ICU, in particular, evaluating the role of iatrogenic factors such as sedatives and analgesic administration in brain dysfunction. This hypothesis is considered along with several other plausible mechanisms of ICU delirium, including sepsis, postoperative cognitive dysfunction, and changes in biomarkers and neurotransmitters. The review concludes by highlighting potential future directions in molecular genetics for the elucidation of delirium and its long-term consequences.
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PMID:Pathophysiology of delirium in the intensive care unit. 1824 78


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