Colonic bacterial translocation as a possible factor in stress-worsening experimental stroke outcome

2009 ◽  
Vol 296 (4) ◽  
pp. R979-R985 ◽  
Author(s):  
Javier R. Caso ◽  
Olivia Hurtado ◽  
Marta P. Pereira ◽  
Borja García-Bueno ◽  
Luis Menchén ◽  
...  
Keyword(s):  
Bacterial Translocation ◽  
Immunoglobulin A ◽  
Experimental Studies ◽  
Intestinal Flora ◽  
Enzyme Activation ◽  
Experimental Stroke ◽  
Main Role ◽  
Stroke Outcome ◽  
Stroke Patients ◽  
Mortality And Morbidity

Stress is known to be one of the risk factors of stroke, but only a few experimental studies have examined the possible mechanisms by which prior stress may affect stroke outcome. In stroke patients, infections impede neurological recovery and increase morbidity as well as mortality. We previously reported that stress induces a bacterial translocation and that prior immobilization stress worsens experimental stroke outcome through mechanisms that involve inflammatory mediators such as release of proinflammatory cytokines and enzyme activation. We now investigate whether bacterial translocation from the intestinal flora of rats with stress before experimental ischemia is involved in stroke outcome. We used an experimental paradigm consisting of exposure of Fischer rats to repeated immobilization sessions before permanent middle cerebral artery occlusion (MCAO). The presence of bacteria and the levels and expression of different mediators involved in the bacterial translocation were analyzed. Our results indicate that stress before stroke is related to the presence of bacteria in different organs (mesenteric nodes, spleen, liver, and lung) after MCAO and increases inflammatory colonic parameters (such as cyclooxygenase-2, inducible nitric oxide synthase, and myeloperoxidase), but decreases colonic immunoglobulin A, and these results are correlated with colonic inflammation and bacterial translocation. Understanding the implication of bacterial translocation during stress-induced stroke worsening is of great potential clinical relevance, given the high incidence of infections after severe stroke and their main role in mortality and morbidity in stroke patients.

scholarly journals Comorbidity and age in the modelling of stroke: are we still failing to consider the characteristics of stroke patients?

2020 ◽  
Vol 4 (1) ◽  
pp. e100013 ◽  
Author(s):  
Sarah K McCann ◽  
Catherine B Lawrence
Keyword(s):  
Infarct Volume ◽  
Treatment Options ◽  
Response To Treatment ◽  
Experimental Stroke ◽  
Preclinical Studies ◽  
Stroke Patients ◽  
Mortality And Morbidity ◽  
Degree Of Protection ◽  
Stroke Research ◽  
Drug Interventions

Stroke is a significant cause of mortality and morbidity for which there are limited treatment options. Virtually all drug interventions that have been successful preclinically in experimental stroke have failed to translate to an effective treatment in the clinical setting. In this review, we examine one of the factors likely contributing to this lack of translation, the failure of preclinical studies to consider fully the advanced age and comorbidities (eg, hypertension or diabetes) present in most patients with stroke. Age and comorbidities affect the likelihood of suffering a stroke, disease progression and the response to treatment. Analysing data from preclinical systematic reviews of interventions for ischaemic stroke we show that only 11.4% of studies included an aged or comorbid model, with hypertension being the most frequent. The degree of protection (% reduction in infarct volume) varied depending on the comorbidity and the type of intervention. We consider reasons for the lack of attention to comorbid and aged animals in stroke research and discuss the value of testing a potential therapy in models representing a range of comorbidities that affect patients with stroke. These models can help establish any limits to a treatment’s efficacy and inform the design of clinical trials in appropriate patient populations.

scholarly journals Adrenergic-mediated loss of splenic marginal zone B cells contributes to infection susceptibility after stroke

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Laura McCulloch ◽  
Craig J. Smith ◽  
Barry W. McColl
Keyword(s):  
B Cells ◽  
Marginal Zone ◽  
Major Complication ◽  
Experimental Stroke ◽  
Stroke Patients ◽  
Marginal Zone B Cells ◽  
Mortality And Morbidity ◽  
Susceptibility To Infection ◽  
Infection Susceptibility ◽  
Improve Clinical Outcome

Abstract Infection is a major complication of acute stroke and causes increased mortality and morbidity; however, current interventions do not prevent infection and improve clinical outcome in stroke patients. The mechanisms that underlie susceptibility to infection in these patients are unclear. Splenic marginal zone (MZ) B cells are innate-like lymphocytes that provide early defence against bacterial infection. Here we show experimental stroke in mice induces a marked loss of MZ B cells, deficiencies in capturing blood-borne antigen and suppression of circulating IgM. These deficits are accompanied by spontaneous bacterial lung infection. IgM levels are similarly suppressed in stroke patients. β-adrenergic receptor antagonism after experimental stroke prevents loss of splenic MZ B cells, preserves IgM levels, and reduces bacterial burden. These findings suggest that adrenergic-mediated loss of MZ B cells contributes to the infection-prone state after stroke and identify systemic B-cell disruption as a target for therapeutic manipulation.

scholarly journals Is age a key factor contributing to the disparity between success of neuroprotective strategies in young animals and limited success in elderly stroke patients? Focus on protein homeostasis

2017 ◽  
Vol 37 (10) ◽  
pp. 3318-3324 ◽  
Author(s):  
Wei Yang ◽  
Wulf Paschen
Keyword(s):  
Medical Community ◽  
Experimental Stroke ◽  
Protein Homeostasis ◽  
Stroke Outcome ◽  
Self Healing ◽  
Cellular Functions ◽  
Stroke Patients ◽  
Limited Success ◽  
Neuroprotective Strategies ◽  
Ischemic Stress

Neuroprotection strategies to improve stroke outcome have been successful in the laboratory but not in clinical stroke trials, and thus have come under scrutiny by the medical community. Experimental stroke investigators are therefore under increased pressure to resolve this problem. Acute ischemic stroke represents a severe form of metabolic stress that activates many pathological processes and thereby impairs cellular functions. Traditionally, neuroprotection strategies were designed to improve stroke outcome by interfering with pathological processes triggered by ischemia. However, stroke outcome is also dependent on the brain’s capacity to restore cellular functions impaired by ischemia, and this capacity declines with age. It is, therefore, conceivable that this age-dependent decline in the brain’s self-healing capacity contributes to the disparity between the success of neuroprotective strategies in young animals, and limited success in elderly stroke patients. Here, prosurvival pathways that restore protein homeostasis impaired by ischemic stress should be considered, because their capacity decreases with increasing age, and maintenance of proteome fidelity is pivotal for cell survival. Boosting such prosurvival pathways pharmacologically to restore protein homeostasis and, thereby, cellular functions impaired by ischemic stress is expected to counterbalance the compromised self-healing capacity of aged brains and thereby help to improve stroke outcome.

scholarly journals The Role of Glutamine in the Complex Interaction between Gut Microbiota and Health: A Narrative Review

2019 ◽  
Vol 20 (20) ◽  
pp. 5232 ◽  
Author(s):  
Simone Perna ◽  
Tariq A. Alalwan ◽  
Zahraa Alaali ◽  
Tahera Alnashaba ◽  
Clara Gasparri ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Bacterial Translocation ◽  
Immunoglobulin A ◽  
Experimental Studies ◽  
Bacterial Overgrowth ◽  
Intestinal Lumen ◽  
Glutamine Supplementation ◽  
Potential Applications

The scientific literature has demonstrated that glutamine is one of the main beneficial amino acids. It plays an important role in gut microbiota and immunity. This paper provides a critical overview of experimental studies (in vitro, in vivo, and clinical) investigating the efficacy of glutamine and its effect on gut microbiota. As a result of this review, we have summarized that glutamine could affect gut microbiota via different mechanisms including the reduction in the ratio of Firmicutes to Bacteroidetes, with the activation of NF-κB and PI3K-Akt pathways, reducing the intestinal colonization (Eimeria lesions) and bacterial overgrowth or bacterial translocation, increasing the production of secretory immunoglobulin A (SIgA) and immunoglobulin A+ (IgA+) cells in the intestinal lumen, and decreasing asparagine levels. The potential applications of glutamine on gut microbiota include, but are not limited to, the management of obesity, bacterial translocation and community, cytokines profiles, and the management of side effects during post-chemotherapy and constipation periods. Further studies and reviews are needed regarding the effects of glutamine supplementation on other conditions in humans.

Addiction and Liver Disease

2014 ◽  
Vol 25 (2) ◽  
pp. 75-83
Author(s):  
Md Akmat Ali ◽  
Farida Yeasmin ◽  
MN Nag
Keyword(s):  
Liver Disease ◽  
Liver Diseases ◽  
Drug Users ◽  
Harmful Effect ◽  
Main Role ◽  
Drug Induced ◽  
Mortality And Morbidity ◽  
Other Substances ◽  
Excessive Alcohol ◽  
Medicine Today

Drug induced liver disease is a global problem. The aims of the study are to know the recreational drugs causing harmful effect on liver, epidemiology of addiction; pathophysiology and their consequences. The major findings published to date concerning different agents causing addiction and liver disease, their implications with regard to understanding disease mechanisms and their amplitude or spectrum are described. Addiction not only invites lot of sufferings to the family and the country, but also responsible for different types of liver disease including fatty liver, hepatitis and liver failure; responsible for mortality and morbidity. Among the addiction causing substances alcohol playing the main role for liver disease worldwide. Indirect effects of addiction on liver are hepatitis B, hepatitis C and their complication, mainly due to contamination of sharing needle. Majority of people in Bangladesh are life long abstainer. Excessive alcohol beverages and other substances like heroin, amphetamine are not harmless, rather they can cause serious liver diseases. There are some differences in prevalence of addiction and liver diseases among countries. Intravenous drug users are affected both directly and indirectly due to contaminated needle sharing . DOI: http://dx.doi.org/10.3329/medtoday.v25i2.17926 Medicine Today 2013 Vol.25(2): 75-83

Preterm Birth, Inflammation and Infection: New Alternative Strategies for their Prevention

2019 ◽  
Vol 20 (5) ◽  
pp. 354-365 ◽  
Author(s):  
Víctor M. Muñoz-Pérez ◽  
Mario I. Ortiz ◽  
Raquel Cariño-Cortés ◽  
Eduardo Fernández-Martínez ◽  
Leticia Rocha-Zavaleta ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Medicinal Plants ◽  
Low Income ◽  
Experimental Studies ◽  
Neonatal Outcomes ◽  
New Drugs ◽  
Alternative Strategies ◽  
Mortality And Morbidity ◽  
Therapeutic Benefits ◽  
Gynecology And Obstetrics

Background:Worldwide, the progress in reducing neonatal mortality has been very slow. The rate of preterm birth has increased over the last 20 years in low-income and middle-income countries. Its association with increased mortality and morbidity is based on experimental studies and neonatal outcomes from countries with socioeconomic differences, which have considered implementing alternative healthcare strategies to prevent and reduce preterm births.Methods:Currently, there is no widely effective strategy to prevent preterm birth. Pharmacological therapies are directed at inhibiting myometrial contractions to prolong parturition. Some drugs, medicinal plants and microorganisms possess myorelaxant, anti-inflammatory and immunomodulatory properties that have proved useful in preventing preterm birth associated with inflammation and infection.Results:This review focuses on the existing literature regarding the use of different drugs, medicinal plants, and microorganisms that show promising benefits for the prevention of preterm birth associated with inflammation and infection. New alternative strategies involving the use of PDE-4 inhibitors, medicinal plants and probiotics could have a great impact on improving prenatal and neonatal outcomes and give babies the best start in life, ensuring lifelong health benefits.Conclusion:Despite promising results from well-documented cases, only a small number of these alternative strategies have been studied in clinical trials. The development of new drugs and the use of medicinal plants and probiotics for the treatment and/or prevention of preterm birth is an area of growing interest due to their potential therapeutic benefits in the field of gynecology and obstetrics.

Functional outcome after intracerebral haemorrhage – a review of the potential role of antiapoptotic agents

2016 ◽  
Vol 27 (3) ◽  
pp. 317-327 ◽  
Author(s):  
Abubakar Tijjani Salihu ◽  
Sangu Muthuraju ◽  
Zamzuri Idris ◽  
Abdul Rahman Izaini Ghani ◽  
Jafri Malin Abdullah
Keyword(s):  
Functional Outcome ◽  
Intracerebral Haemorrhage ◽  
Neuronal Death ◽  
Potential Role ◽  
Management Strategies ◽  
Experimental Studies ◽  
Neuronal Loss ◽  
Multimodality Treatment ◽  
Mortality And Morbidity

AbstractIntracerebral haemorrhage (ICH) is the second most common form of stroke and is associated with greater mortality and morbidity compared with ischaemic stroke. The current ICH management strategies, which mainly target primary injury mechanisms, have not been shown to improve patient’s functional outcome. Consequently, multimodality treatment approaches that will focus on both primary and secondary pathophysiology have been suggested. During the last decade, a proliferation of experimental studies has demonstrated the role of apoptosis in secondary neuronal loss at the periphery of the clot after ICH. Subsequently, the value of certain antiapoptotic agents in reducing neuronal death and improving functional outcome following ICH was evaluated in animal models. Preliminary evidence from those studies strongly supports the potential role of antiapoptotic agents in reducing neuronal death and improving functional outcome after intracerebral haemorrhage. Expectedly, the ongoing and subsequent clinical trials will substantiate these findings and provide clear information on the most potent and safe antiapoptotic agents, their appropriate dosage, and temporal window of action, thereby making them suitable for the multimodality treatment approach.

7,8-Dihydroxyflavone and Neuropsychiatric Disorders: A Translational Perspective from the Mechanism to Drug Development

2021 ◽  
Vol 19 ◽  
Author(s):  
Shaojie Yang ◽  
Guoqi Zhu
Keyword(s):  
Drug Development ◽  
Memory Function ◽  
Experimental Studies ◽  
Intestinal Flora ◽  
Neuropsychiatric Disorders ◽  
Tyrosine Kinase Receptor ◽  
Downstream Signaling ◽  
Clinical Drug Development ◽  
Clinical Drug

: 7,8-Dihydroxyflavone (7,8-DHF) is a kind of natural flavonoids, with the potential to cross the blood-brain barrier. 7,8-DHF effectively mimics the effect of brain-derived neurotrophic factor (BDNF) in the brain to selectively activate tyrosine kinase receptor B (TrkB) and downstream signaling pathways, thus playing a neuroprotective role. The preclinical effects of 7,8-DHF have been widely investigated in the neuropsychiatric disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), depression and memory impairment. Besides the effect on TrkB, 7,8-DHF could also function through fighting against oxidative stress, cooperating with estrogen receptors or regulating intestinal flora. This review focuses on the recent experimental studies on depression, neurodegenerative diseases and learning and memory function. Additionally, the structural modification and preparation of 7,8-DHF were also concluded and proposed, hoping to provide reference for the follow-up research and clinical drug development of 7,8-DHF in the field of neuropsychiatric disorders.

scholarly journals Different Strokes for Different Folks: The Rich Diversity of Animal Models of Focal Cerebral Ischemia

2010 ◽  
Vol 30 (8) ◽  
pp. 1412-1431 ◽  
Author(s):  
David W Howells ◽  
Michelle J Porritt ◽  
Sarah SJ Rewell ◽  
Victoria O'Collins ◽  
Emily S Sena ◽  
...  
Keyword(s):  
Animal Model ◽  
Ischemic Stroke ◽  
Animal Models ◽  
Focal Cerebral Ischemia ◽  
Experimental Stroke ◽  
Stroke Outcome ◽  
Rich Diversity ◽  
Single Animal ◽  
The Rich ◽  
Use Of Models

No single animal model is able to encompass all of the variables known to affect human ischemic stroke. This review highlights the major strengths and weaknesses of the most commonly used animal models of acute ischemic stroke in the context of matching model and experimental aim. Particular emphasis is placed on the relationships between outcome and underlying vascular variability, physiologic control, and use of models of comorbidity. The aim is to provide, for novice and expert alike, an overview of the key controllable determinants of experimental stroke outcome to help ensure the most effective application of animal models to translational research.

scholarly journals Brain-derived neurotrophic factor in peripheral blood mononuclear cells and stroke outcome

2018 ◽  
Vol 243 (15-16) ◽  
pp. 1207-1211 ◽  
Author(s):  
Martin Pedard ◽  
Céline Brenière ◽  
Nicolas Pernet ◽  
Catherine Vergely ◽  
Yannick Béjot ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Outcome ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Stroke Outcome ◽  
Stroke Patients ◽  
Peripheral Blood Mononuclear ◽  
Ischemic Brain ◽  
Blood Mononuclear Cells

Stroke outcome is dependent on brain-derived neurotrophic factor (BDNF)-dependent neuroplasticity. As peripheral blood mononuclear cells (PBMC) contain BDNF, diapedesis of these cells might be followed by BDNF delivery to the ischemic brain. To test this hypothesis, we investigated the association between BDNF levels in PBMC and functional outcome in patients with ischemic stroke. BDNF was measured in PBMC that were isolated from ischemic stroke patients ( n = 40) just before (day 0) and after (days 1 and 3) fibrinolysis. Three months after stroke, patients were stratified using the modified Rankin Scale (mRS) according to the unfavorable (mRS scores 3–6) and favorable (mRS scores 0–2) functional outcome. We used univariate and multivariate logistic regressions to assess the relationship between BDNF levels in PBMC and functional outcome. BDNF levels in PBMC decreased from day 0 to day 3 in patients with unfavorable outcome, while they remained stable in patients with favorable outcome. Patients with favorable outcome exhibited at day 3 higher PBMC-BDNF levels than patients with unfavorable outcome and the levels were associated with good outcome (odd ratio: 12.0; 95% confidence interval, 1.4–106.2, P = 0.023). PBMC-BDNF levels remained a predictor of stroke outcome after adjusting from cardiovascular risk, interval between admission and fibrinolysis, stroke severity from hospital admission to discharge, lymphocytes count, neutrophils/lymphocytes ratio at admission. Favorable functional outcome in ischemic stroke patients that benefited from fibrinolysis was predicted by a high BDNF level in PBMC, suggesting that PBMC might serve as a cellular vector to deliver BDNF to the ischemic brain. Impact statement There are a great number of arguments suggesting that BDNF could be involved in stroke recovery dependent of neuroplasticity. Methods that can enhance BDNF levels in the ischemic brain could therefore have great clinical value. Peripheral blood mononuclear cells (PBMC) that contain BDNF and infiltrate early and sustainably the ischemic brain might be used as a cellular vector to deliver BDNF to the ischemic brain and consequently promote recovery. This work is important in this field to show if this BDNF derived from BDNF could exert a positive action on stroke recovery. Our main results showed that a high BDNF level at day 3 after hospital admission was associated with a 12.4 fold increase in favorable outcome after adjusting for still recognized prognostic markers. The new information in this field is this finding identifies PBMC as an attractive cellular vector to deliver BDNF to the ischemic brain.

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