scholarly journals Lipids and Lipid Mediators Associated with the Risk and Pathology of Ischemic Stroke

2020 ◽  
Vol 21 (10) ◽  
pp. 3618 ◽  
Author(s):  
Anna Kloska ◽  
Marcelina Malinowska ◽  
Magdalena Gabig-Cimińska ◽  
Joanna Jakóbkiewicz-Banecka
Keyword(s):  
Fatty Acids ◽  
Ischemic Stroke ◽  
Brain Tissue ◽  
Lipid Mediators ◽  
Normal Brain ◽  
Stroke Treatment ◽  
Post Stroke ◽  
Increased Risk ◽  
Risk Biomarkers ◽  
And Function

Stroke is a severe neurological disorder in humans that results from an interruption of the blood supply to the brain. Worldwide, stoke affects over 100 million people each year and is the second largest contributor to disability. Dyslipidemia is a modifiable risk factor for stroke that is associated with an increased risk of the disease. Traditional and non-traditional lipid measures are proposed as biomarkers for the better detection of subclinical disease. In the central nervous system, lipids and lipid mediators are essential to sustain the normal brain tissue structure and function. Pathways leading to post-stroke brain deterioration include the metabolism of polyunsaturated fatty acids. A variety of lipid mediators are generated from fatty acids and these molecules may have either neuroprotective or neurodegenerative effects on the post-stroke brain tissue; therefore, they largely contribute to the outcome and recovery from stroke. In this review, we provide an overview of serum lipids associated with the risk of ischemic stroke. We also discuss the role of lipid mediators, with particular emphasis on eicosanoids, in the pathology of ischemic stroke. Finally, we summarize the latest research on potential targets in lipid metabolic pathways for ischemic stroke treatment and on the development of new stroke risk biomarkers for use in clinical practice.

Abstract T P228: Ischemic Stroke Results in Increased Activity of the Neuroprotective Angiotensin Converting Enzyme 2 in Rat Brain and Serum

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Douglas M Bennion ◽  
Emily Haltigan ◽  
Alexander J Irwin ◽  
Daniel L Purich ◽  
Colin Sumners
Keyword(s):  
Cerebral Cortex ◽  
Ischemic Stroke ◽  
Angiotensin Converting Enzyme ◽  
Rat Cerebral Cortex ◽  
Mrna Levels ◽  
Converting Enzyme ◽  
Stroke Treatment ◽  
Angiotensin Converting Enzyme 2 ◽  
Post Stroke ◽  
Rebound Increase

Background: Recent studies show that pharmacological induction of the angiotensin converting enzyme 2/angiotensin-(1-7)/mas [ACE2-Ang-(1-7)-Mas] axis, a protective pathway of the renin angiotensin system, elicits neuroprotection in ischemic stroke. However, endogenous levels and activity of the components of this axis in the brain and serum following stroke are not well established. Here, we assessed the post-stroke activity and expression of ACE2 in rat cerebral cortex and serum after ischemic stroke in rats, in the absence or presence of an ACE2 activator. Methods: Sprague Dawley rats underwent sham surgery or endothelin-1-induced middle cerebral artery occlusion (ET-1 MCAO). Activity of ACE2 was analyzed within serum and cerebral cortical tissue samples using a fluorometric assay, and mRNA levels were assessed by qRT-PCR. In an additional experiment, rats received daily intraperitoneal administration of diminazene aceturate (DIZE), a putative ACE2 activator, or vehicle after ET-1 MCAO. Data are normalized to corresponding control values and expressed as means ± SEM with a significance of p<0.05. Results: ACE2 activity levels were significantly increased in ischemic brain cortex at 4, 12, and 24 h after a stroke (4h: 237.1±46.1%; 12h: 212.4±12.8%; 24h: 191.6±19.1%) versus rats with sham strokes. Paradoxically, there was a significant decrease in ACE2 mRNA levels in the ischemic cortex at 24h (0.71±0.1) compared to shams (1.0±0.08). After decreasing in activity at 4h after stroke, serum ACE2 activity was increased at 24h in stroked rats (96.08±9.4%) versus shams (70.80±7.1%). Post-stroke treatment with DIZE (7.5 mg/kg) resulted in significantly increased ACE2 activity in serum (213.7±49.8%) versus controls, two days following stroke. Conclusions: Activity of the protective enzyme ACE2 is increased in rat cerebral cortex following stroke, with a rebound increase in serum activity. Post-stroke treatment with an ACE2 activator resulted in significantly increased ACE2 activity in serum. These results suggest that stroke therapeutics designed to target the ACE2/Ang-(1-7)/Mas axis may act in synergy with endogenous changes in the acute post-stroke setting, lending promise to their further study as potential neuroprotective agents.

scholarly journals Neutrophil-to-Lymphocyte Ratio and Symptomatic Hemorrhagic Transformation in Ischemic Stroke Patients Undergoing Revascularization

2020 ◽  
Vol 10 (11) ◽  
pp. 771
Author(s):  
Milena Świtońska ◽  
Natalia Piekuś-Słomka ◽  
Artur Słomka ◽  
Paweł Sokal ◽  
Ewa Żekanowska ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Multivariable Analysis ◽  
Area Under The Curve ◽  
Intravenous Thrombolysis ◽  
Hemorrhagic Transformation ◽  
Neutrophil To Lymphocyte Ratio ◽  
Study Endpoint ◽  
Stroke Treatment ◽  
Lymphocyte Ratio ◽  
Increased Risk

Objectives: Symptomatic hemorrhagic transformation (sHT) is a life-threatening complication of acute ischemic stroke (AIS). The early identification of the patients at increased risk of sHT can have clinically relevant implications. The aim of this study was to explore the validity and accuracy of the neutrophil-to-lymphocyte ratio (NLR) in predicting sHT in patients with AIS undergoing revascularization. Methods: Consecutive patients hospitalized for AIS who underwent intravenous thrombolysis, mechanical thrombectomy or both were identified. The NLR values were estimated at admission. The study endpoint was the occurrence of sHT within 24 h from stroke treatment. Results: Fifty-one patients with AIS were included, with a median age of 67 (interquartile range, 55–78) years. sHT occurred in 10 (19.6%) patients. Patients who developed sHT had higher NLR at admission. NLR was an independent predictor of sHT and showed good discriminatory power (area under the curve 0.81). In a multivariable analysis, NLR and systolic blood pressure were independently associated with sHT. Conclusions: NLR at admission can accurately predict sHT in patients with AIS undergoing revascularization.

scholarly journals Fluoride Exposure Induces Inhibition of Sodium-and Potassium-Activated Adenosine Triphosphatase (Na+, K+-ATPase) Enzyme Activity: Molecular Mechanisms and Implications for Public Health

2019 ◽  
Vol 16 (8) ◽  
pp. 1427 ◽  
Author(s):  
Declan Timothy Waugh
Keyword(s):  
Enzyme Activity ◽  
Atpase Activity ◽  
Molecular Mechanisms ◽  
Chemical Elements ◽  
Biological Pathways ◽  
Normal Brain ◽  
Biological Interface ◽  
Increased Risk ◽  
And Function ◽  
Risk Of Cancer

In this study, several lines of evidence are provided to show that Na + , K + -ATPase activity exerts vital roles in normal brain development and function and that loss of enzyme activity is implicated in neurodevelopmental, neuropsychiatric and neurodegenerative disorders, as well as increased risk of cancer, metabolic, pulmonary and cardiovascular disease. Evidence is presented to show that fluoride (F) inhibits Na + , K + -ATPase activity by altering biological pathways through modifying the expression of genes and the activity of glycolytic enzymes, metalloenzymes, hormones, proteins, neuropeptides and cytokines, as well as biological interface interactions that rely on the bioavailability of chemical elements magnesium and manganese to modulate ATP and Na + , K + -ATPase enzyme activity. Taken together, the findings of this study provide unprecedented insights into the molecular mechanisms and biological pathways by which F inhibits Na + , K + -ATPase activity and contributes to the etiology and pathophysiology of diseases associated with impairment of this essential enzyme. Moreover, the findings of this study further suggest that there are windows of susceptibility over the life course where chronic F exposure in pregnancy and early infancy may impair Na + , K + -ATPase activity with both short- and long-term implications for disease and inequalities in health. These findings would warrant considerable attention and potential intervention, not to mention additional research on the potential effects of F intake in contributing to chronic disease.

Localized Brain Tissue Cooling for Use During Intracranial Thrombectomy

2012 ◽  
Author(s):  
Thomas L. Merrill ◽  
Denise R. Merrill ◽  
Jennifer E. Akers
Keyword(s):  
Ischemic Stroke ◽  
Reperfusion Injury ◽  
Brain Tissue ◽  
Ischemic Injury ◽  
Blood Perfusion ◽  
Neuroprotective Agents ◽  
Tissue Necrosis ◽  
Stroke Treatment ◽  
Neurological Outcomes

The primary goal of current ischemic stroke treatment is quickly restoring blood perfusion. Recanalization is linked to improved neurological outcomes [1]. Resulting tissue necrosis, however, following a stroke has two causes: 1) ischemic injury and 2) reperfusion injury. Therefore, development of neuroprotective agents specifically beneficial against reperfusion injury are required.

scholarly journals Top Priorities for Cerebroprotective Studies: A Paradigm Shift

Stroke ◽  
2021 ◽  
Author(s):  
Patrick Lyden ◽  
Alastair Buchan ◽  
Johannes Boltze ◽  
Marc Fisher ◽  
Keyword(s):  
Ischemic Stroke ◽  
Brain Tissue ◽  
Imaging Techniques ◽  
Neurovascular Unit ◽  
Clinical Trial Design ◽  
Clinical Work ◽  
Brain Regions ◽  
Tissue Imaging ◽  
Health Concern ◽  
Stroke Treatment

Despite years of basic research and pioneering clinical work, ischemic stroke remains a major public health concern. Prior STAIR (Stroke Treatment Academic Industry Roundtable) conferences identified both failures of clinical trial design and failures in preclinical assessment in developing putative ischemic stroke treatments. At STAIR XI, participants in workshop no. 1 Top Priorities for Neuroprotection sought to redefine the neuroprotection paradigm and given the paucity of evidence underlying preclinical assessment, offer consensus-based recommendations. STAIR proposes the term brain cytoprotection or cerebroprotection to replace the term neuroprotection when the intention of an investigation is to demonstrate that a new, candidate treatment benefits the entire brain. Although “time is still brain,” tissue imaging techniques have been developed to identify patients with both predicted core injury and penumbral, salvageable brain tissue, regardless of time after stroke symptom onset. STAIR XI workshop participants called this imaging approach a tissue window to select patients for recanalization. Elements of the neurovascular unit show differential vulnerability evolving over differing time scales in different brain regions. STAIR proposes the term target window to suggest therapies that target the different elements of the neurovascular unit at different times. Based on contemporary principles of rigor and transparency, the workshop updated, revised, and enhanced the STAIR preclinical recommendations for developing new treatments in 2 phases: an exploratory qualification phase and a definitive validation phase. For new, putative treatments, investigators should carefully characterize the mechanism of action, the pharmacokinetics/pharmacodynamics, demonstrate target engagement, and confirm penetration through the blood-brain barrier. Before clinical trials, testing of candidate molecules in stroke models could proceed in a comprehensive manner using animals of both sexes and to include significant variables such as age and comorbid conditions. Comprehensive preclinical assessment might include multicenter, collaborative testing, for example, network trials. In the absence of a proven cerebroprotective agent to use as a gold standard, however, it remains speculative whether such comprehensive preclinical assessment can effectively predict clinical outcome.

scholarly journals Augmentation of peripheral lymphocyte-derived cholinergic activity in patients with acute ischemic stroke

BMC Neurology ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Meng Yuan ◽  
Bin Han ◽  
Yiping Xia ◽  
Ye Liu ◽  
Chunyang Wang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Stroke ◽  
Acute Ischemic Stroke ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Brain Infarction ◽  
Cholinergic Activity ◽  
Post Stroke ◽  
Increased Risk ◽  
Cholinergic Pathway

Abstract Background Brain ischemia activates the parasympathetic cholinergic pathway in animal models of human disease. However, it remains unknown whether activation of the cholinergic pathway impacts immune defenses and disease outcomes in patients with ischemic stroke. This study investigated a possible association between peripheral cholinergic activity, post-stroke infection, and mortality. Methods In this study, we enrolled 458 patients with acute ischemic stroke (< 24 h after onset), 320 patients with ischemic stroke on day 10, and 216 healthy subjects. Peripheral cholinergic activity, reflected by intracellular acetylcholine (ACh) content in human peripheral blood mononuclear cells (PBMCs), was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Expression of acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) was measured by quantitative real-time PCR and western blot. Regression analyses were used to assess associations between peripheral cholinergic function and clinical outcomes. Results Within 24 h after the onset of acute ischemic stroke, there was a rapid increase in peripheral cholinergic activity that correlated with brain infarction volume (r = 0.67, P < 0.01). Specifically, lymphocyte-derived ACh levels were significantly higher in stroke patients with pneumonia (0.21 ± 0.02 ng/106 PBMC versus 0.15 ± 0.01 ng/106 PBMC, P = 0.03). Of note, lymphocytic AChE catalytic activity was significantly lower in these patients. One-year mortality was significantly greater in patients with higher intracellular ACh levels within the first 24 h after acute stroke. Conclusions Lymphocytes produced increased amounts of ACh in patients with acute stroke, and pneumonia was a likely result. The association between this enhanced cholinergic activity and increased risk of pneumonia/mortality suggests that increased cholinergic activity may contribute to fatal post-stroke infection.

Abstract 19922: Phosphatidylserine Receptor Upregulation in Stroke for Targeted Carrier Delivery

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Tao Peng ◽  
David D McPherson ◽  
Shao-Ling Huang
Keyword(s):  
Endothelial Cells ◽  
Cerebral Ischemia ◽  
Brain Tissue ◽  
Umbilical Vein ◽  
Brain Cells ◽  
Normal Brain ◽  
Necrosis Factor Alpha ◽  
Stroke Treatment ◽  
Early Stages ◽  
Phosphatidylserine Receptor

Introduction: The phosphatidylserine receptor (PSR) plays an important role in apoptosis and inflammation. Whether this receptor is expressed in damaged brain cells in the early stages of stroke is unknown. Hypothesis: The purpose of this study was to determine if this receptor is expressed on ischemic neurovascular endothelial cells and if so, can it bind with PS-containing liposomes (PS-liposomes). The latter would allow for a neurovascular targeting strategy for therapeutic delivery to ischemic brain cells. Methods: Sprague Dawley rats (n=22) were randomly divided into sham, cerebral ischemia, and subarachnoid hemorrhage (SAH) injury groups. Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 2 hours using an intraluminal suture method. SAH was induced by an endovascular perforation method. Brain tissue was harvested for immunofluorescence staining at day 2 after surgery. Cultured human umbilical vein endothelial cells (HUVEC) were pre-treated with tumor necrosis factor alpha (TNFα) to stimulated PSR. Fluorescence labeled PS-containing liposomes (FITC-PS-Liposomes) were used. The PSR expression and the adhesion of liposomes were observed using fluorescence microscopy. Results: Normal brain tissue did not demonstrate PSR expression (Fig.1A). After brain injury, PSR expression was observed in the injured area and colocalized with the endothelium both in the MCAO (Fig.1B) and SAH animals (Fig.1C). Normal HUVEC did not demonstrate fluorescence (Fig.1D). Weak fluorescence was observed in normal cells that incorporated the PS-liposomes (Fig.1E). Strong fluorescence was observed in the TNFα-activated HUVEC that incorporated the FITC-PS-Liposomes (Fig.1F). Conclusions: This is first report that PSR expression occurs in cerebral microvascular endothelial cells in the early stages of stroke and can be recognized by PS-liposomes. This may allow development of a targeted liposomal carrier for novel targeted stroke treatment.

scholarly journals Adipogenesis and lipotoxicity: role of peroxisome proliferator-activated receptor γ (PPARγ) and PPARγcoactivator-1 (PGC1)

2007 ◽  
Vol 10 (10A) ◽  
pp. 1132-1137 ◽  
Author(s):  
Gema Medina-Gomez ◽  
Sarah Gray ◽  
Antonio Vidal-Puig
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Peroxisome Proliferator ◽  
Metabolic Complications ◽  
Peroxisome Proliferator Activated Receptor ◽  
Toxic Response ◽  
Increased Risk ◽  
And Function

AbstractObesity is characterised by an increase in the adipose deposits, resulting from an imbalance between food intake and energy expenditure. When expansion of the adipose tissue reaches its maximum limit, as in obesity, fat accumulates in non-adipose tissues such as liver, heart, muscle and pancreas, developing a toxic response known as lipotoxicity, a condition that promotes the development of insulin resistance and other metabolic complications. Thus, the lipotoxic state may contribute to the increased risk of insulin resistance, diabetes, fatty liver and cardiovascular complications associated with obesity.We are interested in studying adipose tissue, specifically how mechanisms of adipogenesis and remodelling of adipose tissue, in terms of size and function of the adipocytes, could be considered a strategy to increase the capacity for lipid storage and prevent lipotoxicity. The peroxisome proliferator-activated receptors (PPARs) are a family of transcription factors that regulate energy balance by promoting either energy deposition or energy dissipation. Under normal physiological conditions, PPARγ is mainly expressed in adipose tissue and regulates diverse functions such as the development of fat cells and their capacity to store lipids. The generation of PPARγ knockout mice, either tissue specific or isoform specific, has provided new models to study PPARγ’s role in adipose tissue differentiation and function and have highlighted the essential role of PPARγ in adipogenesis and lipogenesis.A second strategy to prevent lipotoxicity is to increase the capacity of tissues to oxidise fatty acids. PPARγcoactivator-1α is a coactivator of PPARγ that induces the expression of genes that promote the differentiation of preadipocytes to brown adipocytes. Recently, it has been implicated in increasing the oxidation of fatty acids via increasing mitochondrial capacity and function, making this co-factor a key candidate for the treatment of lipotoxicity.

scholarly journals Umbilical cord mesenchymal stem cells limit post-stroke infection

2021 ◽  
Author(s):  
Jianbang Han ◽  
Yu Xie ◽  
Zhiming Feng ◽  
Haitao Sun ◽  
Feng Li ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Brain Injury ◽  
Nk Cells ◽  
Umbilical Cord ◽  
Stroke Treatment ◽  
Post Stroke ◽  
Increased Risk ◽  
Activated State ◽  
The Brain

Abstract Background Brain ischemia leads to excessive infiltration of clusters of CD8+ T and natural killer (NK) cells in the brain, which aggravate ischemic brain injury. Acute ischemic stroke also has a negative impact on the antibacterial immune response, leading to stroke-induced immunodepression and infection. Umbilical cord mesenchymal stem cell (ucMSC) have an immunosuppressive function. Therefore, we aimed to determine whether ucMSC treatment alleviates the excessive infiltration of CD8+ T and NK cells. We also investigated significant concerns that ucMSC treatment might suppress antimicrobial immunity, leading to an increased risk of infection. Methods After middle cerebral artery occlusion, stroke and post-stroke infective mice received intravenous injection of ucMSC. We performed haematoxylin and eosin staining of organs and assessed the Modified Neurological Severity Score (mNSS),the activated state of microglia,quantity and distribution of CD8 + T and NK cells. Changes of cytokines (IL-6, TNF-α, IL-10), and blood biochemical indexes were also detected.We then assessed autophagy and apoptosis of platelets, as well as mitochondrial membrane potential (MMP) and ATP levels.In vitro ucMSC was co-cultured with platelet and Escherichia coli, followed by detection of the E. coli growth curve. Results ucMSC treatment ameliorated the infiltration of CD8+ T and NK cells in the brain, reduced levels of proinflammatory cytokines, and increased anti-inflammatory cytokines.ucMSC treatment limit post-stroke infection and reduce the inflmamatory injury of various organs induced by post-stroke infection,as well as ucMSC inhibit the growth of Escherichia coli in vivo and vitro.ucMSC treatment maintained autophagy, MMP, and the production of ATP, while inhibiting apoptosis of platelets in vivo. Conclusions Based on these findings, ucMSC may represent a potential and safe therapeutic option for stroke treatment by inhibiting brain injury and limiting post-stroke infection.

scholarly journals RISK OF POST STROKE PNEUMONIA DURING HOSPITALIZATION

2021 ◽  
Vol 4 (IAHSC) ◽  
pp. 108-113
Author(s):  
Juliana Gracia G.E.P Massie ◽  
Ratna Sitorus ◽  
I Made Kariasa ◽  
Yunisar Gultom ◽  
Maya Khairani ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Discrimination Performance ◽  
Diagnostic Study ◽  
Common Complication ◽  
Stroke Patients ◽  
Cross Sectional ◽  
Post Stroke ◽  
Increased Risk ◽  
Nursing Team

Introduction: Post-stroke pneumonia is the most a common complication during the first few weeks after a stroke. Thus, a score is needed for the early identification of stroke patients with an increased risk of pneumonia to assist the nursing team in preventing the onset of pneumonia in stroke patients during hospitalization. This study aimed to assess the application of the A2DS2 score to predict pneumonia in acute ischemic stroke patients. Method: This is a diagnostic study that used a cross-sectional method conducted among adult acute ischemic stroke patients. Data analysis was performed to assess the calibration and discrimination performance of the A2DS2 score. Results: A total of 16 respondents were followed up. The incidence of post-stroke pneumonia was observed in 6 patients (37.5%). Conclusion: This scoring proved clinically accurate to predict the incidence of pneumonia in acute ischemic stroke patients.

Sign in / Sign up

Export Citation Format

Share Document