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brain dysfunction sepsis

Timothy D Girard, Jennifer L Thompson, Pratik P Pandharipande, Nathan E Brummel, James C Jackson, Mayur B Patel, Christopher G Hughes, Rameela Chandrasekhar, Brenda T Pun, Leanne M Boehm, Mark R Elstad, Richard B Goodman, Gordon R Bernard, Robert S Dittus, E W Ely
BACKGROUND: Delirium during critical illness results from numerous insults, which might be interconnected and yet individually contribute to long-term cognitive impairment. We sought to describe the prevalence and duration of clinical phenotypes of delirium (ie, phenotypes defined by clinical risk factors) and to understand associations between these clinical phenotypes and severity of subsequent long-term cognitive impairment. METHODS: In this multicentre, prospective cohort study, we included adult (≥18 years) medical or surgical ICU patients with respiratory failure, shock, or both as part of two parallel studies: the Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors (BRAIN-ICU) study, and the Delirium and Dementia in Veterans Surviving ICU Care (MIND-ICU) study...
March 2018: Lancet Respiratory Medicine
Wei Xing, Pinjie Huang, Yang Lu, Weian Zeng, Zhiyi Zuo
Amantadine has been shown to reduce anesthesia and surgery-induced neuroinflammation and cognitive dysfunction. It is known that sepsis can impair brain function. We determined whether amantadine-attenuated sepsis-induced neuroinflammation and dysfunction of learning and memory and whether toll-like receptors (TLRs) play a role in the effects. Six- to eight-week-old mice were subjected to cecal ligation and puncture (CLP). Amantadine at 30 mg/kg/day was injected intraperitoneally for 3 days. CU-CPT22, a TLR1/TLR2 inhibitor, at 3 mg/kg/day was injected intraperitoneally for 2 days...
March 3, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Masaaki Kawakami, Mizuki Hattori, Wakana Ohashi, Toshio Fujimori, Kohshi Hattori, Mariko Takebe, Kengo Tomita, Hiroki Yokoo, Naoyuki Matsuda, Mitsuaki Yamazaki, Yuichi Hattori
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-GPCR-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...
March 3, 2018: Journal of Neurochemistry
Katharina Rump, Michael Adamzik
Background: Sepsis is a common cause of death in intensive care units worldwide. Due to the high complexity of this immunological syndrome development of novel therapeutic strategies is urgent. Promising drug targets or biomarkers may depict aquaporins (AQPs) as they regulate crucial key mechanisms of sepsis. Main body: Here we report on base of the current literature that several AQPs are involved in different physiological processes of sepsis. In immune system mainly AQPs 3, 5 and 9 seem to be important, as they regulate the migration of different immune cells...
2018: Cell & Bioscience
Maha Gamal, Jackline Moawad, Laila Rashid, Mary Attia Morcos, Nivin Sharawy
BACKGROUND AND AIM: Tetrahydrobiopterin (BH4) is an essential co-factor that regulates nitric oxide (NO) and reactive oxygen species (ROS) production by nitric oxidesynthases (NOS). In this study, we evaluated the effects of sepsis on BH 4 level and redox status in the brain by using the rat model of sepsis- induced by cecal ligation and puncture (CLP) and examined whether BH4 and/or acetyl-L-carnitine(ALC) could prevent the neuronal apoptosis and neurological changes induced by sepsis...
February 8, 2018: Brain Research
Rheal A Towner, D Saunders, N Smith, W Towler, M Cruz, S Do, J E Maher, K Whitaker, M Lerner, K A Morton
Sepsis-associated encephalopathy (SAE) induces neuroinflammation, which is associated with cognitive impairment (CI). CI is also correlated with aging. We used contrast-enhanced magnetic resonance imaging (MRI), perfusion MRI, and MR spectroscopy to assess long-term alterations in BBB permeability, microvascularity, and metabolism, respectively, in a rat lipopolysaccharide-induced SAE model. Free radical-targeted molecular MRI was used to detect brain radical levels at 24 h and 1 week post-LPS injection. CE-MRI showed increased Gd-DTPA uptake in LPS rat brains at 24 h in cerebral cortex, hippocampus, thalamus, and perirhinal cortex regions...
February 7, 2018: GeroScience
Khalil Hajiasgharzadeh, Behzad Baradaran
The hepatic vagus branches innervate the liver and serve an important role in liver-brain connection. It appears that brain modulates inflammatory responses by activation of vagal efferent fibers. This activation and subsequent acetylcholine releases from vagus nerve terminals leads to inhibition of inflammatory cytokines through α7 nicotinic acetylcholine receptors (α7nAChRs) which located on the surface of different cell types such as liver Kupffer cells. This protective role of vagus-α7nAChR axis in liver diseases has been shown in several experimental studies...
December 2017: Advanced Pharmaceutical Bulletin
Deep Chandh Raja, Sanjay Mehrotra, Avinash Agrawal, Abhishek Singh, Kamlesh Kumar Sawlani
Objectives: Cardiac biomarkers have been studied in sepsis in the past and various mechanisms for their rise have been elucidated. However their association with severity of sepsis, mortality and myocardial dysfunction warrants further studies. We have studied three different cardiac biomarkers- troponin T (trop T), creatine phosphokinase MB isoform (CPK MB) and NT pro brain natriuretic peptide (NT Pro BNP) in patients with septicemia. We have attempted to observe the levels of these biomarkers in sepsis, their individual abilities to predict the severity of sepsis, mortality and association with myocardial dysfunction noted in echocardiography...
December 2017: Journal of the Association of Physicians of India
M Winkelmann, W Soechtig, C Macke, C Schroeter, J D Clausen, C Zeckey, C Krettek, P Mommsen
PURPOSE: Patients with multiple injuries are particularly susceptible to accidental hypothermia which is correlated with an increased risk of post-traumatic complications and mortality; however, its impact on neurological outcome in cases where there is concomitant traumatic brain injury is underexplored. METHODS: We analyzed severely injured patients (ISS ≥ 16) including a moderate-to-severe traumatic brain injury (AISHead ≥ 3). The primary endpoint was objective neurological recovery, expressed as Glasgow Outcome Scale (GOS) score at time of discharge...
January 9, 2018: European Journal of Trauma and Emergency Surgery: Official Publication of the European Trauma Society
Figen Esen, Perihan Ergin Ozcan, Erdem Tuzun, M Dustin Boone
Acute brain dysfunction associated with sepsis is a serious complication that results in morbidity and mortality. Intravenous immunoglobulin (IVIg) treatment is known to alleviate behavioral deficits in the experimentally induced model of sepsis. To delineate the mechanisms by which IVIg treatment prevents neuronal dysfunction, an array of immunological and apoptosis markers was investigated. Our results suggest that IVIgG and IgGAM administration ameliorates neuronal dysfunction and behavioral deficits by reducing apoptotic cell death and glial cell proliferation...
December 12, 2017: Reviews in the Neurosciences
Benjamin H Singer, Robert P Dickson, Scott J Denstaedt, Michael W Newstead, Kwi Kim, Nicole R Falkowski, John R Erb-Downward, Thomas M Schmidt, Gary B Huffnagle, Theodore J Standiford
RATIONALE: Sepsis causes brain dysfunction and neuroinflammation. It is unknown whether neuroinflammation in sepsis is initiated by dissemination of bacteria to the brain and sustained by persistent infection, or whether neuroinflammation is a sterile process resulting solely from circulating inflammatory mediators. OBJECTIVES: To determine if gut bacteria translocate to the brain during sepsis, and are associated with neuroinflammation. METHODS: Murine sepsis was induced using cecal ligation and puncture, and sepsis survivor mice were compared with sham and unoperated control animals...
March 15, 2018: American Journal of Respiratory and Critical Care Medicine
Mu-Huo Ji, De-Guo Xia, Lan-Yue Zhu, Xia Zhu, Xiao-Yan Zhou, Jiang-Yan Xia, Jian-Jun Yang
Brain dysfunction is a common complication after sepsis and is an independent risk factor for a poor prognosis, which is partly attributed to the dysregulated inflammatory response and oxidative damage. Melatonin regulates the sleep-wake cycle and also has potent anti-inflammatory and antioxidant properties, yet the protective effects of melatonin on sepsis-induced neurobehavioral dysfunction remain to be elucidated. In the present study, melatonin was administered intraperitoneally daily at a dose of 10 mg/kg for three consecutive days immediately (early treatment) or 7 days (delayed treatment) after sham operation or cecal ligation and puncture (CLP), followed by an additional treatment in drinking water until the end of behavioral tests...
December 2, 2017: Inflammation
Chao Ren, Ya-Lin Tong, Jun-Cong Li, Ning Dong, Ji-Wei Hao, Qing-Hong Zhang, Yong-Ming Yao
Sepsis induced brain injury acts as an acute complication and accounts for deterioration and high mortality rate of septic condition. HMGB1 is a late inflammatory mediator that plays a critical role in brain dysfunction and diseases. However, the role of HMGB1 in sepsis induced brain dysfunction remains intricate. The current study investigated the effect of HMGB1 on brain injury in septic mice model with intracerebroventricular injection of BoxA (a specific antagonist of HMGB1). The expression of HMGB1, morphological changes of brain tissues, apoptosis of brain cells, and alteration of behavior were determined...
November 3, 2017: Oncotarget
Shuibing Zhang, Xueqin Wang, Sha Ai, Wen Ouyang, Yuan Le, Jianbin Tong
BACKGROUND: Sepsis-induced neuroinflammation plays an important role in sepsis-related brain dysfunction. However, the molecules that are targeted during neuroinflammation resulting from sepsis-induced brain dysfunction remain unclear. Herein, we tried to investigate the expression and roles of NMDA receptor subunits during sepsis-related brain dysfunction. METHODS: Sepsis was induced by cecal ligation and perforation (CLP) or by a single intraperitoneal injection of lipopolysaccharide (LPS, 8 mg/kg) in C57BL/6J mice...
2017: PloS One
Ibtihel Dhaya, Marion Griton, Gérard Raffard, Mohamed Amri, Bassem Hiba, Jan Pieter Konsman
To better understand brain dysfunction during sepsis, cerebral arterial blood flow was assessed with Phase Contrast Magnetic Resonance Imaging, perfusion with Arterial Spin Labeling and structure with diffusion-weighted Magnetic Resonance Imaging in rats after intraperitoneal administration of bacterial lipopolysaccharides. Although cerebral arterial flow was not altered, perfusion of the corpus callosum region and diffusion parallel to its fibers were higher after lipopolysaccharide administration as compared to saline injection...
January 15, 2018: Journal of Neuroimmunology
Mu-Huo Ji, Hui Tang, Dan Luo, Li-Li Qiu, Min Jia, Hong-Mei Yuan, Shan-Wu Feng, Jian-Jun Yang
Brain dysfunction remains a common complication after sepsis development and is an independent risk factor for a poorer prognosis and an increased mortality. Here we tested the hypothesis that the behavioral outcomes after lipopolysaccharides (LPS) administration are exacerbated by an impoverished environment (IE) and alleviated by an enriched environment (EE), respectively. Mice were randomly allocated in a standard environment (SE), an EE, or an IE for 4 weeks after LPS or normal saline (NS) administration...
October 10, 2017: Oncotarget
Juciano Gasparotto, Carolina S Girardi, Nauana Somensi, Camila T Ribeiro, José C F Moreira, Monique Michels, Beatriz Sonai, Mariane Rocha, Amanda V Steckert, Tatiana Barichello, João Quevedo, Felipe Dal-Pizzol, Daniel P Gelain
Patients recovering from sepsis have higher rates of CNS morbidities associated with long-lasting impairment of cognitive functions, including neurodegenerative diseases. However, the molecular etiology of these sepsis-induced impairments is unclear. Here, we investigated the role of the receptor for advanced glycation end products (RAGE) in neuroinflammation, neurodegeneration-associated changes, and cognitive dysfunction arising after sepsis recovery. Adult Wistar rats underwent cecal ligation and perforation (CLP), and serum and brain (hippocampus and prefrontal cortex) samples were obtained at days 1, 15, and 30 after the CLP...
January 5, 2018: Journal of Biological Chemistry
Johannes Ehler, Lucinda K Barrett, Valerie Taylor, Michael Groves, Francesco Scaravilli, Matthias Wittstock, Stephan Kolbaske, Annette Grossmann, Jörg Henschel, Martin Gloger, Tarek Sharshar, Fabrice Chretien, Francoise Gray, Gabriele Nöldge-Schomburg, Mervyn Singer, Martin Sauer, Axel Petzold
BACKGROUND: Brain homeostasis deteriorates in sepsis, giving rise to a mostly reversible sepsis-associated encephalopathy (SAE). Some survivors experience chronic cognitive dysfunction thought to be caused by permanent brain injury. In this study, we investigated neuroaxonal pathology in sepsis. METHODS: We conducted a longitudinal, prospective translational study involving (1) experimental sepsis in an animal model; (2) postmortem studies of brain from patients with sepsis; and (3) a prospective, longitudinal human sepsis cohort study at university laboratory and intensive care units (ICUs)...
October 23, 2017: Critical Care: the Official Journal of the Critical Care Forum
Q Feng, L Wu, Y H Ai, S Y Deng, M L Ai, L Huang, Z Y Liu, L N Zhang
Objective: To investigate the diagnostic value of neuron-specific enolase(NSE), central nervous system specific protein(S100β), interleukin-6(IL-6) in sepsis-associated encephalopathy(SAE). Methods: Clinical data of patients admitted to ICU and diagnosed with sepsis were collected from January 2015 to June 2016 in Xiangya Hospital, Central South University. SAE was defined as cerebral dysfunction in the presence of sepsis that also fulfilled the exclusion criteria. The acute physiology and chronic health score (APACHE Ⅱ), sequential organ failure assessment (SOFA), NSE, S100β, IL-6, ICU stay time and 28-day mortality were compared between the two groups...
October 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
H X Ma, X J Shi, Y R Liang, H D Shi, H Wang, Y S Zhao
Objective: To study the clinical characteristics of sepsis with systemic capillary leak syndrome(SCLS) and to evaluate the therapeutic effect and clinical significance of fluid therapy adjusted timely in these patients. Methods: The clinical data of 34 patients with sepsis and SCLS in the Department of Hepatobiliary Surgery ICU of General Hospital of People's Liberation Army General Hospital from July 2014 to January 2016 were retrospectively analyzed.There were 21 males and 13 females, aged from 21 to 74 years, with an average age of 56...
September 1, 2017: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
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