Tumor necrosis factor alpha serum levels and inflammatory response in acute ischemic stroke patients

Intiso, Domenico; Zarrelli, Michele; Lagioia, G.; Rienzo, Filomena Di; Ambrosio, C. Checchia De; Simone, P.; Tonali, P.; Cioffi, Raffaella

doi:10.1007/s10072-003-0194-z

Cited by 105 publications

(58 citation statements)

References 38 publications

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“…33 TNF-a release from blood cells and serum levels of TNF-a were found to be elevated during the acute phase following stroke compared with healthy controls. [34][35][36] Furthermore, increased levels of TNF-a in the cerebral spinal fluid and serum of acute stroke patients has been associated with increased severity of postischemic neuropathology 37 and polymorphism of the TNF gene have been associated with susceptibility to ischemic stroke. 32 IL-6 is a pleiotropic cytokine involved in inflammatory processes and like IL-1 is able to induce acute inflammatory responses such as fibrinogen and C-reactive protein production.…”

Section: Resultsmentioning

confidence: 99%

The etiology of poststroke depression: a review of the literature and a new hypothesis involving inflammatory cytokines

et al. 2006

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Although poststroke depression is unlikely to represent a single disorder and numerous etiologies for different kinds of poststroke depression will likely emerge as the result of future research, we believe that a number of poststroke depressive disorders are likely to be the result of specific changes in brain pathology and neurophysiology. Nevertheless, there are relatively few hypotheses about the pathophysiology of poststroke depression. This paper, therefore, proposes a new hypothesis for poststroke depression involving increased production of proinflammatory cytokines resulting from brain ischemia in cerebral areas linked to the pathogenesis of mood disorders. This paper reviews the evidence supporting the hypothesis that proinflammatory cytokines are involved in the occurrence of stroke as well as mood disorders linked to the brain damage. The increased production of proinflammatory cytokines such as IL-1b, TNF-a or IL-18 resulting from stroke may lead to an amplification of the inflammatory process, particularly in limbic areas, and widespread activation of indoleamine 2,3-dioxygenase (IDO) and subsequently to depletion of serotonin in paralimbic regions such as the ventral lateral frontal cortex, polar temporal cortex and basal ganglia. The resultant physiological dysfunction may lead to poststroke depression. Future investigations may explore this hypothesis through more extensive studies on the role of proinflammatory cytokines, such as IL-1b, TNF-a or even IL-18, in patients with poststroke depression. Molecular Psychiatry (2006) 11, 984-991.

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Section: Resultsmentioning

confidence: 99%

The etiology of poststroke depression: a review of the literature and a new hypothesis involving inflammatory cytokines

et al. 2006

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“…On the other, they can facilitate thrombogenesis by increasing the levels of plasminogenactivating inhibitor-1 tissue factor (PAI-1), and platelet activating factor and by inhibiting tissue plasminogen activator and protein [121]. Clinical studies [122,123] have reported increased levels of proinflammatory cytokines and adhesion molecules in the peripheral blood and cerebrospinal fluid (CSF) of patients with ischemic stroke. Among the cytokines involved in the pathogenesis of ischemic stroke, TNF-is activated in experimental ischemia at both the mRNA and protein levels.…”

Section: Inflammation In Acute Stroke Subtypesmentioning

confidence: 99%

Inflammation in Ischemic Stroke Subtypes

Tuttolomondo

Raimondo²,

Pecoraro³

et al. 2012

CPD

127

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Determining the cause of stroke does influence choices for management. categorization of subtypes of ischemic stroke has had considerable study, but definitions are hard to formulate and their application for diagnosis in an individual patient is often problematic. Cerebral ischemia initiates a complex cascade of events at genomic, molecular, and cellular levels, and inflammation is important in this cascade. In 1993 for For the Trial of Org 10172 in Acute Stroke Treatment (TOAST), Adams et al] conducted a placebo-controlled, randomized, blinded study of the low-molecular-weight heparinoid given to patients within 24 hours after stroke and developed a system for diagnosis of subtype of ischemic stroke that uses components of existing diagnostic schemes. The type of acute ischemic stroke was classified according to the TOAST classification: 1) Large Artery AtheroSclerosis (LAAS); 2) CardioEmbolic Infarct (CEI); 3) LACunar infarct (LAC); 4) stroke of Other Determined Etiology (ODE); 5) stroke of UnDetermined Etiology (UDE) (see Fig. (1)). On the basis of pathophysiologic differences of each stroke subtype it's possible to hypothesize a different pattern of immuno-inflammatory activation in relation of ischemic stroke subtype. A nonspecific systemic inflammatory response occurs after both ischemic and hemorrhagic stroke, either as part of the process of brain damage or in response to complications such as deep venous thrombosis. Several studies have reported that higher levels of inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) are associated with worse outcome after ischemic stroke.Our group reported that patients with cardioembolic subtype showed significantly higher median plasma levels of TNF-, IL-6, IL-1 whereas the lacunar subtype showed significantly lower median plasma levels of TNF-, IL-6 and IL-1 . Our findings underlined the significant association was noted between the severity of neurological deficit at admission, the diagnostic subtype and some inflammatory variables.

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“…Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (Intiso et al, 2004). On the other hand, TNF-α is also produced in brain, by microglia and astrocytes, both of which are activated by LPS.…”

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confidence: 99%

“…during stroke (Intiso et al, 2004). On the other hand, TNF-α is also produced in brain, by microglia and astrocytes, both of which are activated by LPS.…”

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confidence: 99%

TNF is a key mediator of septic encephalopathy acting through its receptor, TNF receptor-1

Alexander

Jacob

Cunningham

et al. 2008

Neurochemistry International

196

141

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In this study, we demonstrate that mice deficient in TNFR1 (TNFR1 -/-) were resistant to LPSinduced encephalopathy. Systemic administration of lipopolysaccharide (LPS) induces a widespread inflammatory response similar to that observed in sepsis. Following LPS administration TNFR1 -/-mice had less caspase-dependent apoptosis in brain cells and fewer neutrophils infiltrating the brain (p<0.039), compared to control C57Bl6 (TNFR1 +/+ ) mice. TNFR1-dependent increase in aquaporin (AQP)-4 mRNA and protein expression was observed with a concomitant increase in water content, in brain (18% increase in C57Bl6 mice treated with LPS vs those treated with saline), similar to cerebral edema observed in sepsis. Furthermore, absence of TNFR1 partially but significantly reduced the activation of astrocytes, as shown by immunofluorescence and markedly inhibited iNOS mRNA expression (p<0.01).Septic Encephalopathy is a devastating complication of sepsis. Although, considerable work has been done to identify the mechanism causing the pathological alterations in this setting, the culprit still remains an enigma. Our results demonstrate for the first time that endotoxemia leads to inflammation in brain, with alteration in blood-brain barrier, up-regulation of AQP4 and associated edema, neutrophil infiltration, astrocytosis, as well as apoptotic cellular death, all of which appear to be mediated by TNF-α signaling through TNFR1. KeywordsRodent; Septic Encephalopathy; Lipopolysaccharide; Apoptosis; Aquaporin 4 Neuroimmunology Sepsis is a condition characterized by uncontrolled infection and affects many organs including brain (Green et al., 2004), with an attendant high mortality rate. Administration of bacterial endotoxin (LPS), a cell wall component of gram-negative bacteria, to mice cause pathogenesis, mimicking what occurs in clinical sepsis (Gardenfors et al., 2002;Radzivil et al., 1990). Septic encephalopathy could be due to multiple factors including inflammatory cells and their mediators, reduced cerebral blood flow, disruption of the blood-brain barrier (BBB), cerebral edema and inflammation (Papadopoulos et al., 2000). One of the mediators of inflammation that play a key role in sepsis, tumor necrosis factor (TNF-α), is increased in circulation following LPS administration (Tsao et al., 2001;Merrill and Benveniste, 1996). Serum TNF-α is an acute phase response and does not correlate with the alterations in brain, Address correspondence and reprint requests to Dr. Jessy J. Alexander, Department of Medicine, University of Chicago, 5841 South Maryland Avenue, MC5100, Chicago, IL 60637. jalexand@medicine.bsd.uchicago.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered w...

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Tumor necrosis factor alpha serum levels and inflammatory response in acute ischemic stroke patients

Cited by 105 publications

References 38 publications

The etiology of poststroke depression: a review of the literature and a new hypothesis involving inflammatory cytokines

The etiology of poststroke depression: a review of the literature and a new hypothesis involving inflammatory cytokines

Inflammation in Ischemic Stroke Subtypes

TNF is a key mediator of septic encephalopathy acting through its receptor, TNF receptor-1

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