Neurology of Sepsis

Sweis, Rochelle; Ortiz, Jorge G.; Biller, José

doi:10.1007/s11910-016-0623-z

Cited by 23 publications

(16 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In sepsis, thus, uncontrolled, excessive, and overwhelming systemic inflammation can lead to impaired function of vital organs, including the brain (Sweis et al . ; Hattori et al . ).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Role of G protein‐coupled receptor kinase 2 in oxidative and nitrosative stress‐related neurohistopathological changes in a mouse model of sepsis‐associated encephalopathy

Kawakami

Hattori

Ohashi

et al. 2018

Journal of Neurochemistry

View full text Add to dashboard Cite

Sepsis-associated encephalopathy (SAE), characterized as diffuse brain dysfunction and neurological manifestations secondary to sepsis, is a common complication in critically ill patients and can give rise to poor outcome, but understanding the molecular basis of this disorder remains a major challenge. Given the emerging role of G protein-coupled receptor 2 (GRK2), first identified as a G protein-coupled receptor (GPCR) regulator, in the regulation of non-G protein-coupled receptor-related molecules contributing to diverse cellular functions and pathology, including inflammation, we tested the hypothesis that GRK2 may be linked to the neuropathogenesis of SAE. When mouse MG6 microglial cells were challenged with lipopolysaccharide (LPS), GRK2 cytosolic expression was highly up-regulated. The ablation of GRK2 by small interfering RNAs (siRNAs) prevented an increase in intracellular reactive oxygen species generation in LPS-stimulated MG6 cells. Furthermore, the LPS-induced up-regulation of inducible nitric-oxide synthase expression and increase in nitric oxide production were negated by GRK2 inhibitor or siRNAs. However, GRK2 inhibition was without effect on overproduction of tumor necrosis factor-α, interleukin (IL)-6, and IL-1β in LPS-stimulated MG cells. In mice with cecal ligation and puncture-induced sepsis, treatment with GRK2 inhibitor reduced high levels of oxidative and nitrosative stress in the mice brains, where GRK2 expression was up-regulated, alleviated neurohistological damage observed in cerebral cortex sections, and conferred a significant survival advantage to CLP mice. Altogether, these results uncover the novel role for GRK2 in regulating cellular oxidative and nitrosative stress during inflammation and suggest that GRK2 may have a potential as an intriguing therapeutic target to prevent or treat SAE.

show abstract

“…In sepsis, thus, uncontrolled, excessive, and overwhelming systemic inflammation can lead to impaired function of vital organs, including the brain (Sweis et al . ; Hattori et al . ).…”

mentioning

confidence: 99%

“…Its neurological symptoms vary from lethargy and delirium to coma (Sweis et al . ), and, despite the most frequently observed form of encephalopathy in ICUs, the incidence of SAE also varies from 9% to 71% of septic patients, probably depending on the inclusion of criteria employed (Siami et al . ).…”

mentioning

confidence: 99%

Role of G protein‐coupled receptor kinase 2 in oxidative and nitrosative stress‐related neurohistopathological changes in a mouse model of sepsis‐associated encephalopathy

Kawakami

Hattori

Ohashi

et al. 2018

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…The first step upon SAE suspicion in a hospitalized patient would be a neurological examination to identify acute changes in mental status, cognition, sleep patterns, and disorganized thinking. Other alarm signs are agitation, paratonic rigidity, hallucinations, and coma …”

Section: Human Sepsis and Saementioning

confidence: 99%

Sepsis: developing new alternatives to reduce neuroinflammation and attenuate brain injury

Meneses

Cárdenas

Espinosa

et al. 2018

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

Sepsis occurs when a systemic infection induces an uncontrolled inflammatory response that results in generalized organ dysfunction. The exacerbated peripheral inflammation can induce, in turn, neuroinflammation which may result in severe impairment of the central nervous system (CNS). Indeed, the ensuing blood–brain barrier disruption associated with sepsis promotes glial activation and starts a storm of proinflammatory cytokines in the CNS that leads to brain dysfunction in sepsis survivors. Endotoxic shock induced in mice by peripheral injection of lipopolysaccharides closely resembles the peripheral and central inflammation observed in sepsis. In this review, we provide an overview of the neuroinflammatory features in sepsis and of recent progress toward the development of new anti‐neuroinflammatory therapies seeking to reduce mortality and morbidity in sepsis survivors.

show abstract

“… 34 found that intestinal microecological conditions’ change can also induce septic encephalopathy, although their main focus was on the vagal function, the cortical neurons glial cell inflammatory response to the pathogenesis of sepsis encephalopathy was studied. Previous studies have shown that electroencephalogram in patients with sepsis encephalopathy has its characteristic changes 35 . In general, we use α, β, θ, δ four waveforms to describe the pathophysiological state of the brain, α, β waves can be found in patients with clear and sleep, while δ wave prone to patients with sepsis encephalopathy 36 .…”

Section: Disscussionmentioning

confidence: 99%

Intraperitoneal hypertension, a novel risk factor for sepsis-associated encephalopathy in sepsis mice

et al. 2018

Sci Rep

View full text Add to dashboard Cite

Sepsis associated encephalopathy (SAE), appears often indicates the deterioration of the sepsis disease and which have high risk of death. Although several mechanism and hypotheses have been proposed and studied, there is no breakthrough in the treatment of SAE. We performed a systematic research to evaluate the effect of intraperitoneal pressure on SAE. A mice model of sepsis was established by intraperitoneal injection of endotoxin. A total of 48 female BALB/c mouse (30 days old) were randomly divided into a control group (n = 12) and an injection of endotoxin referred to bacterial lipopolysaccharide (LPS) group (n = 12). Intraperitoneal hypertension (IAH) referred to IAH group (n = 12), and LPS + IAH group (n = 12). Following sepsis induction, diagnosis, the brains were analyzed for both function and ultrastructural morphology.We determined that IAH exacerbated sepsis induces sepsis-associated encephalopathy when examining low score of neurological function and more delta wave in EEG, increased neuronal edema in LPS + IAH group, as well as an escalation of Bax and Cleaved-caspase-3, Cleaved-parp, and reduction of Bcl-2 and Mfsd2a in LPS + IAH group. Therefore, IAH can exacerbate and increase incident rate of sepsis-related encephalopathy in sepsis mice by promoting neuronal apoptosis and destruction of the blood-brain barrier.

show abstract

Neurology of Sepsis

Cited by 23 publications

References 61 publications

Role of G protein‐coupled receptor kinase 2 in oxidative and nitrosative stress‐related neurohistopathological changes in a mouse model of sepsis‐associated encephalopathy

Role of G protein‐coupled receptor kinase 2 in oxidative and nitrosative stress‐related neurohistopathological changes in a mouse model of sepsis‐associated encephalopathy

Sepsis: developing new alternatives to reduce neuroinflammation and attenuate brain injury

Intraperitoneal hypertension, a novel risk factor for sepsis-associated encephalopathy in sepsis mice

Contact Info

Product

Resources

About