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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

While peripheral immune access to the central nervous system (CNS) is restricted and tightly controlled, the CNS is capable of dynamic immune and inflammatory responses to a variety of insults. Infections, trauma, stroke, toxins and other stimuli are capable of producing an immediate and short lived activation of the innate immune system within the CNS. This acute neuroinflammatory response includes activation of the resident immune cells (microglia) resulting in a phagocytic phenotype and the release of inflammatory mediators such as cytokines and chemokines. While an acute insult may trigger oxidative and nitrosative stress, it is typically short-lived and unlikely to be detrimental to long-term neuronal survival. In contrast, chronic neuroinflammation is a long-standing and often self-perpetuating neuroinflammatory response that persists long after an initial injury or insult. Chronic neuroinflammation includes not only long-standing activation of microglia and subsequent sustained release of inflammatory mediators, but also the resulting increased oxidative and nitrosative stress. The sustained release of inflammatory mediators works to perpetuate the inflammatory cycle, activating additional microglia, promoting their proliferation, and resulting in further release of inflammatory factors. Neurodegenerative CNS disorders, including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), tauopathies, and age-related macular degeneration (ARMD), are associated with chronic neuroinflammation and elevated levels of several cytokines. Here we review the hallmarks of acute and chronic inflammatory responses in the CNS, the reasons why microglial activation represents a convergence point for diverse stimuli that may promote or compromise neuronal survival, and the epidemiologic, pharmacologic and genetic evidence implicating neuroinflammation in the pathophysiology of several neurodegenerative diseases.
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PMID:Does neuroinflammation fan the flame in neurodegenerative diseases? 1991 31

The scientific community is fully aware of the importance of heat-related illness and heat stroke syndrome. Numerous guidelines have been recently published and most of them agree on the key role played by the intestine. Likewise, the role of endotoxinemia in the pathophysiology is well established. However, the possibility of bacterial translocation is not mentioned. Our patient illustrates the likelihood of bacterial translocation in heat stroke and consistently the potential need of antibiotic therapy. A 45-year-old man diagnosed with paranoid schizophrenia was confined in a penitentiary center. One summer day in which a temperature of 41 degrees C was observed in the shade, the patient was found in deep coma with an axillary temperature of 42 degrees C. Multiorgan failure was detected in the hospital. Other causes of coma and/or hyperthermia were excluded, and heat stroke was diagnosed. Blood cultures were positive for Pseudomonas aeruginosa and Escherichia coli. Infection site was not identified despite of an exhaustive search. The patient fully recovered after 48 hours. On the basis of review of the literature, we think that bacterial translocation can take part in the pathophysiology of heat stroke. Therefore, antibiotic treatment must be evaluated in heat stroke patients.
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PMID:Bacterial translocation in heat stroke. 1993 77

Infection is the commonest complication of stroke and has a major impact on morbidity and mortality. The relationships between susceptibility to infection after stroke and the influence of infection on stroke outcome are complex, but have considerable clinical relevance. Both pharmacological and non-pharmacological interventions in acute stroke may affect the risk of developing infection by influencing potentially modifiable risk factors, for example exposure to infectious organisms (dysphagia/aspiration), or immune susceptibility to infectious challenge. Treatment of infection itself may also reduce ischaemic injury, and influence outcome following stroke. In this review we discuss the role of current and emerging treatments for stroke and their effects on infection, considering possible underlying mechanisms and implications for the development of new therapies.
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PMID:Current and emerging treatments for acute stroke: relationships with infection. 2016 69

Infectious diseases are the most common medical complication after cerebral ischemia, inpairing both the neurological and the general medical outcome. The most frequent infectious complications are bacterial pneumonia and urinary tract infections. There is a growing body of evidence that a secondary immunosuppressive state accounts for the increased risk of infection following stroke. Infections do not only have an important impact on outcome after stroke but also are known risk factors for stroke. Thus, suitable models for investigating the relation between infections and stroke are urgently needed. Elucidating the underlying mechanisms might facilitate the development of new therapeutic strategies and improve patient outcome. Here we present recent insights into the relationship between infections and stroke, based on experimental models of post-stroke infection. In addition we give a brief overview of models that explore the impact on stroke of preceding infections.
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PMID:Models of infection before and after stroke: investigating new targets. 2016 71

Infections occur commonly following stroke and adversely influence outcome. Dysphagia, greater stroke severity and increasing age are associated with post-stroke infection, but post-stroke immunodepression is now recognised as an independent factor associated with increased susceptibility. Counter-regulatory responses, triggered by the pro-inflammatory response to stroke, appear to effect systemic immunodepression via suppression of both innate and adaptive immune responses. Experimental and clinical studies have identified a range of anti-inflammatory and immunosuppressive changes, including reduced mononuclear phagocyte and natural killer cell function, induction of anti-inflammatory cytokines, apoptotic lymphocyte loss and altered T lymphocyte activity. A range of mechanisms has been proposed, including hypothalamo-pituitary-adrenal axis (HPAA) and sympathetic nervous system (SNS) activation. The post-stroke balance of pro- and anti- inflammatory mechanisms may be aimed at restricting the extent of inflammation and contributing to the restoration of immune homeostasis. However, severe inflammation in the brain may trigger major systemic, counter-inflammatory responses that ultimately compromise immune mechanisms required to combat pathogens. Although key pathways have been identified, the extent to which the various elements of post-stroke immunodepression are clinically relevant remains to be discovered. The identification of markers of immunodepression in the early post-stroke phase may prove useful for identifying patients that may have increased susceptibility to infection. It also seems likely that post-stroke immunodepression will need to be taken into account where stroke treatments impact upon inflammatory and immune pathways.
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PMID:Post-stroke immunodepression and infection: an emerging concept. 2016 72

Previous studies have demonstrated that benefits of intensive statin therapy compared to standard statin therapy begin shortly after an acute event and are continued up to 2 years of follow-up. However, whether efficacy and safety of intensive statin therapy in patients with a recent cardiac event are maintained in longer-term follow-up has not been evaluated. We conducted a post hoc analysis of a subgroup of 999 patients who had a first acute myocardial infarction (MI) <2 months before randomization in a prospective, open-label, blinded end-point evaluation trial of 8,888 patients with a history of MI that compared intensive statin therapy (atorvastatin 80 mg) to standard statin therapy (simvastatin 20 to 40 mg) over approximately 5 years of follow-up. We analyzed the same composite end point used in the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) trial (death, MI, hospitalization for unstable angina, revascularization, and stroke). Rates of the composite end point were 44.7% (n = 226) in the simvastatin group and 37.9% (n = 187) in the atorvastatin group (hazard ratio 0.82, 95% confidence interval 0.67 to 0.99, p = 0.04). Although statistical power was smaller than that of the PROVE IT trial, the relative risk decrease observed at 5 years is consistent with that in the 2-year follow-up in PROVE IT. The 2 treatment regimens were well tolerated. In conclusion, our analysis provides support for the strategy of placing patients with recent MI on intensive statin therapy and maintaining the high dose over the long term, beyond 2 years.
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PMID:Comparison of atorvastatin 80 mg/day versus simvastatin 20 to 40 mg/day on frequency of cardiovascular events late (five years) after acute myocardial infarction (from the Incremental Decrease in End Points through Aggressive Lipid Lowering [IDEAL] trial). 2064 45

Infection and systemic inflammation are risk factors for cerebrovascular diseases and poststroke infections impair outcome in stroke patients, although the mechanisms of their contribution are mostly unknown. No preclinical studies have identified how chronic infection affects ischemic brain damage and which key inflammatory mediators are involved. We used a well established model of gut infection (Trichuris muris) to study how chronic infection contributes to brain injury. We show that, in mice, infection that leads to a chronic Th1-polarized immune response dramatically (60%) exacerbates brain damage caused by experimental stroke. Chronic Th1-type infection resulted in systemic upregulation of proinflammatory mediators and profoundly altered stroke-induced early (40 min to 4 h) and late (48 h) inflammation in the brain and peripheral tissues. Using the same infection, we show that a Th1-, but not Th2-polarized response augments brain injury by increasing the Th1 chemokine CCL5 [regulated on activation, normal T-cell expressed and secreted (RANTES)] systemically. This infection-associated response paralleled altered regulatory T-cell response, accelerated platelet aggregation in brain capillaries, and increased microvascular injury and matrix metalloproteinase activation after stroke. Antibody neutralization of RANTES reversed the effect of chronic infection on brain damage, microvascular MMP-9 activation, and cellular inflammatory response. Our results suggest that chronic infection exacerbates ischemic brain damage via a RANTES-mediated systemic inflammatory response, which leads to delayed resolution of inflammation and augmented microvascular injury in the brain.
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PMID:Chronic systemic infection exacerbates ischemic brain damage via a CCL5 (regulated on activation, normal T-cell expressed and secreted)-mediated proinflammatory response in mice. 2066 93

Basic and clinical research provides evidence that inflammatory mechanisms play a central role in the pathogenesis and progression of atherosclerosis, plaque rupture, thrombosis, and stroke. Inflammatory biomarkers such as high-sensitivity C-reactive protein have been identified as predictors of first stroke and prognosis after stroke. The value of high-sensitivity C-reactive protein and other markers may depend on the characteristics of the study population; their utility may be less among populations with high vascular risk. A recent randomized, clinical trial suggests that the use of rosuvastatin therapy in otherwise healthy patients with high-sensitivity C-reactive protein >2 mg/dL can reduce the risk of a first stroke by 50%. The prognostic role of high-sensitivity C-reactive protein among patients after stroke, however, is less clear, and other biomarkers, including lipoprotein-associated phospholipase A(2), may provide complementary information about the risk of stroke recurrence. Infections, moreover, may contribute to inflammation and stroke risk. Although no single infectious organism is likely to be identified as the direct cause of atherosclerosis, summary measures of multiple chronic infectious exposures, or "infectious burden," have been associated with the risk of stroke and atherosclerosis affecting the carotid arteries. Acute infections have also been found to serve as stroke triggers in epidemiologic studies. Recommendations to vaccinate patients with cardiovascular disease against influenza represent the first specific anti-infective strategy to be used in vascular prophylaxis. Further studies are needed to determine the role of treatment of inflammation and infection in stroke prevention.
Stroke 2010 Oct
PMID:Inflammatory mechanisms of stroke. 2087 99

Infections after ischemic stroke are known to complicate the clinical course and worsen the outcome. Neuroinflammation is one of the predominant mechanisms of secondary progression of brain injury and infection and is far from being well understood. Experimental data demonstrate that ischemic stroke patients are at a higher risk for systemic infections if they show a pronounced anti-inflammatory response after the event, which is considered an indication of a stress-mediated reduction of immune competence. Only a small number of studies describe the time course of inflammation mediators after ischemic stroke in patients with early poststroke infections. Levels of inflammation mediators after the event of stroke differ, depending on clinical severity and concomitant infectious diseases. Thus, sequential dynamics of early inflammation must be considered in the development of both mechanism-targeting anti-inflammatory and anti-infectious treatment strategies in ischemic brain damage.
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PMID:Linking infection and inflammation in acute ischemic stroke. 2095 34

Traumatic brain injury or stroke causes profound suppression of the cellular immune system and short- and long-term psychological sequelae. Infection is also a common result and is likely caused by bacterial translocation from the gut. Both the bacterial translocation from the gut and the ensuing pneumonia and sepsis are ameliorated by adoptive immune therapy. Huge health care costs are incurred by brain trauma and its sequelae in our soldiers, athletes, and general population. Diffusion tensor imaging and adoptive immune therapy should become standards of care to follow the injured brain serially as it heals and as the immune suppression and infections are overcome. Brain infrastructure healing is retarded by a suppressed immune system, and the blood-brain barrier's response to trauma offers opportunity for adoptive immune therapy to enhance microglial-directed neuronal repair and maintenance.
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PMID:The injured brain: TBI, mTBI, the immune system, and infection: connecting the dots. 2153 56


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