scholarly journals Promising Biomarker Candidates for Cardioembolic Stroke Etiology. A Brief Narrative Review and Current Opinion

2021 ◽  
Vol 12 ◽  
Author(s):  
Arnold Markus ◽  
Schütz Valerie ◽  
Katan Mira
Keyword(s):  
Randomized Clinical Trials ◽  
Thrombus Formation ◽  
Preventive Treatment ◽  
Cardioembolic Stroke ◽  
Prevention Strategies ◽  
Vessel Occlusion ◽  
Cerebral Vessel ◽  
Stroke Etiology ◽  
Underlying Mechanisms ◽  
Made In

Determining the cause of stroke is considered one of the main objectives in evaluating a stroke patient in clinical practice. However, ischemic stroke is a heterogeneous disorder and numerous underlying disorders are implicated in its pathogenesis. Although progress has been made in identifying individual stroke etiology, in many cases underlying mechanisms still remain elusive. Since secondary prevention strategies are tailored toward individual stroke mechanisms, patients whose stroke etiology is unknown may not receive optimal preventive treatment. Cardioembolic stroke is commonly defined as cerebral vessel occlusion by distant embolization arising from thrombus formation in the heart. It accounts for the main proportion of ischemic strokes, and its share to stroke etiology is likely to rise even further in future decades. However, it can be challenging to distinguish cardioembolism from other possible etiologies. As personalized medicine advances, stroke researchers' focus is increasingly drawn to etiology-associated biomarkers. They can provide deeper insight regarding specific stroke mechanisms and can help to unravel previously undetected pathologies. Furthermore, etiology-associated biomarkers could play an important role in guiding future stroke prevention strategies. To achieve this, broad validation of promising candidate biomarkers as well as their implementation in well-designed randomized clinical trials is necessary. This review focuses on the most-promising candidates for diagnosis of cardioembolic stroke. It discusses existing evidence for possible clinical applications of these biomarkers, addresses current challenges, and outlines future perspectives.

Arterial thrombus formation

2010 ◽  
Vol 30 (03) ◽  
pp. 127-135 ◽  
Author(s):  
I. Hagedorn ◽  
T. Vögtle ◽  
B. Nieswandt
Keyword(s):  
Thrombus Formation ◽  
Therapeutic Option ◽  
Coagulation Factor ◽  
Cerebrovascular Diseases ◽  
Vessel Occlusion ◽  
Intracellular Calcium Signaling ◽  
Arterial Thrombus ◽  
Interesting Possibility ◽  
Post Traumatic ◽  
Made In

SummaryPlatelet and coagulation factor-dependent thrombus formation is critical to limit post-traumatic blood loss at sites of vascular injury. However, under pathological conditions like rupture of an atherosclerotic plaque, it may also lead to vessel occlusion causing myocardial infarction or stroke. Therefore, antithrombotic treatment is the prime therapeutic option in the prophylaxis and treatment of ischaemic cardio- and cerebrovascular diseases. The use of existing antithrombotic agents is, however, limited by their inherent effect on primary haemostasis. In recent years, major advances have been made in understanding the mechanisms of thrombus formation in haemostasis and thrombosis and some studies raised the interesting possibility that occlusive thrombus formation and haemo stasis may involve partially different mechanisms. This review briefly summarizes these developments and highlights newly identified mechanisms involved in platelet adhesion and activation, intracellular calcium signaling, integrin activation and initiation of coagulation. The suitability of these pathways as novel targets for antithrombotic therapy is discussed.

A New Model for Quantitative In Vivo Microscopic Analysis of Thrombus Formation and Vascular Recanalisation: The Ear of the Hairless (hr/hr) Mouse

1997 ◽  
Vol 78 (05) ◽  
pp. 1408-1414 ◽  
Author(s):  
Frank Roesken ◽  
Martin Ruecker ◽  
Brigitte Vollmar ◽  
Nicole Boeckel ◽  
Eberhard Morgenstern ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Light Exposure ◽  
Thrombus Formation ◽  
Microscopic Analysis ◽  
Cell Interaction ◽  
Vascular Perfusion ◽  
Vessel Occlusion ◽  
Endothelial Cell Interaction ◽  
Platelet Deposition

SummaryThe alteration of rheological blood properties as well as deterioration of vascular perfusion conditions and cell-cell interactions are major determinants of thrombus formation. Herein, we present an experimental model which allows for quantitative in vivo microscopic analysis of these determinants during both thrombus formation and vascular recanalisation. The model does not require surgical preparation procedures, and enables for repeated analysis of identical microvessels over time periods of days or months, respectively. After i.v. administration of FITC-dextran thrombus formation was induced photochemically by light exposure to individual arterioles and venules of the ear of ten anaesthetised hairless mice. In venules, epiillumination induced rapid thrombus formation with first platelet deposition after 0.59 ± 0.04 min and complete vessel occlusion within 7.48 ±1.31 min. After a 24-h time period, 75% of the thrombosed venules were found recanalised. Marked leukocyte-endothelial cell interaction in those venules indicated persistent endothelial cell activation and/or injury, even after an observation period of 7 days. In arterioles, epi-illumination provoked vasomotion, while thrombus formation was significantly (p <0.05) delayed with first platelet deposition after 2.32 ± 0.22 min and complete vessel occlusion within 20.07 ±3.84 min. Strikingly, only one of the investigated arterioles was found recanalised after 24 h, which, however, did not show leukocyte-endothelial cell interaction. Heparin (300 U/kg, i.v.) effectively counteracted the process of thrombus formation in this model, including both first platelet deposition and vessel occlusion. We conclude that the model of the ear of the hairless mouse allows for distinct in vivo analysis of arteriolar and venular thrombus formation/ recanalisation, and, thus, represents an interesting tool for the study of novel antithrombotic and thrombolytic strategies, respectively.

Effects of multiphase versus single-phase CT angiography for the detection of distal cerebral vessel occlusion

2021 ◽  
Author(s):  
Gerald M. Hefferman ◽  
Grayson L. Baird ◽  
David W. Swenson ◽  
Robert C. Ward ◽  
Mahesh V. Jayaraman ◽  
...  
Keyword(s):  
Ct Angiography ◽  
Single Phase ◽  
Vessel Occlusion ◽  
Cerebral Vessel

EXPRESS: Stent Retriever Alone vs. Aspiration and Stent-Retriever Combination in Large Vessel Occlusion Stroke: A Matched Analysis

2021 ◽  
pp. 174749302110192
Author(s):  
Mahmoud H Mohammaden ◽  
Diogo C. Haussen ◽  
Leonardo Pisani ◽  
Alhamza Al-Bayati ◽  
Aaron Anderson ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Functional Independence ◽  
Stent Retriever ◽  
Sensitivity Analyses ◽  
First Line ◽  
Anterior Circulation ◽  
Vessel Occlusion ◽  
Guide Catheter ◽  
First Pass ◽  
Combined Technique

Background Three randomized clinical trials have reported similar safety and efficacy for contact aspiration (CA) and Stent-retriever (SR) thrombectomy. Aim We aimed to determine whether the Combined Technique (SR+CA) was superior to SR alone as first-line thrombectomy strategy in a patient cohort where balloon-guide catheter was universally used. Methods A prospectively maintained mechanical thrombectomy database from January 2018-December 2019 was reviewed. Patients were included if they had anterior circulation proximal occlusion ischemic stroke (intracranial ICA or MCA-M1/M2 segments) and underwent SR alone thrombectomy or SR+CA as first-line therapy. The primary outcome was the first-pass effect (FPE) (mTICI2c-3). Secondary outcomes included modified FPE (mTICI2b-3), successful reperfusion (mTICI2b-3) prior to and after any rescue strategy, and 90-day functional independence (mRS ≤2). Safety outcomes included rate of parenchymal hematoma (PH) type-2 and 90-day mortality. Sensitivity analyses were performed after dividing the overall cohort according to first-line modality into two matched groups. Results A total of 420 patients were included in the analysis (mean age 64.4 years; median baseline NIHSS 16[11-21]). As compared to first-line SR alone, first-line SR+CA resulted in similar rates of FPE (53% vs. 51%,aOR 1.122, 95%CI[0.745-1.691],p=0.58), mFPE (63% vs. 60.4%,aOR1.250, 95%CI[0.782-2.00],p=0.35), final successful reperfusion (97.6% vs. 98%,p=0.75) and higher chances of successful reperfusion prior to any rescue strategy (81.8% vs. 72.5%,aOR 2.033, 95%CI[1.209-3.419],p=0.007). Functional outcome and safety measures were comparable between both groups. Likewise, the matched analysis (148 patient-pairs) demonstrated comparable results for all clinical and angiographic outcomes except for significantly higher rates of successful reperfusion prior to any rescue strategies with the first-line SR+CA treatment (81.8% vs. 73.6%,aOR 1.881, 95%CI[1.039-3.405],p=0.037). Conclusions Our findings reinforce the findings of ASTER-2 trial in that the first-line thrombectomy with a Combined Technique did not result in increased rates of first-pass reperfusion or better clinical outcomes. However, addition of contact aspiration after initial SR failure might be beneficial in achieving earlier reperfusion.

scholarly journals Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Patricia Soriano Roque ◽  
Mehdi Hooshmandi ◽  
Laura Neagu-Lund ◽  
Shelly Yin ◽  
Noosha Yousefpour ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
General Anesthesia ◽  
Preventive Treatment ◽  
Intranasal Insulin ◽  
Translational Repressor ◽  
Beneficial Effects ◽  
Underlying Mechanisms ◽  
Induced Apoptosis ◽  
Preclinical And Clinical Studies

AbstractLong-lasting cognitive impairment in juveniles undergoing repeated general anesthesia has been observed in numerous preclinical and clinical studies, yet, the underlying mechanisms remain unknown and no preventive treatment is available. We found that daily intranasal insulin administration to juvenile mice for 7 days prior to repeated isoflurane anesthesia rescues deficits in hippocampus-dependent memory and synaptic plasticity in adulthood. Moreover, intranasal insulin prevented anesthesia-induced apoptosis of hippocampal cells, which is thought to underlie cognitive impairment. Inhibition of the mechanistic target of rapamycin complex 1 (mTORC1), a major intracellular effector of insulin receptor, blocked the beneficial effects of intranasal insulin on anesthesia-induced apoptosis. Consistent with this finding, mice lacking mTORC1 downstream translational repressor 4E-BP2 showed no induction of repeated anesthesia-induced apoptosis. Our study demonstrates that intranasal insulin prevents general anesthesia-induced apoptosis of hippocampal cells, and deficits in synaptic plasticity and memory, and suggests that the rescue effect is mediated via mTORC1/4E-BP2 signaling.

scholarly journals The Evolution of Safe and Effective Coaguligands for Vascular Targeting and Precision Thrombosis of Solid Tumors and Vascular Malformations

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 776
Author(s):  
Fahimeh Faqihi ◽  
Marcus A. Stoodley ◽  
Lucinda S. McRobb
Keyword(s):  
Ischemic Stroke ◽  
Targeted Delivery ◽  
Vascular Malformations ◽  
Thrombus Formation ◽  
Developed Countries ◽  
Coagulation Cascade ◽  
Vascular Targeting ◽  
Systemic Delivery ◽  
Vessel Occlusion ◽  
Vessel Patency

In cardiovascular and cerebrovascular biology, control of thrombosis and the coagulation cascade in ischemic stroke, myocardial infarction, and other coagulopathies is the focus of significant research around the world. Ischemic stroke remains one of the largest causes of death and disability in developed countries. Preventing thrombosis and protecting vessel patency is the primary goal. However, utilization of the body’s natural coagulation cascades as an approach for targeted destruction of abnormal, disease-associated vessels and tissues has been increasing over the last 30 years. This vascular targeting approach, often termed “vascular infarction”, describes the deliberate, targeted delivery of a thrombogenic effector to diseased blood vessels with the aim to induce localized activation of the coagulation cascade and stable thrombus formation, leading to vessel occlusion and ablation. As systemic delivery of pro-thrombotic agents may cause consternation amongst traditional stroke researchers, proponents of the approach must suitably establish both efficacy and safety to take this field forward. In this review, we describe the evolution of this field and, with a focus on thrombogenic effectors, summarize the current literature with respect to emerging trends in “coaguligand” development, in targeted tumor vessel destruction, and in expansion of the approach to the treatment of brain vascular malformations.

scholarly journals Efficacy and Safety of Intravenous rtPA in Ischemic Strokes Due to Small-Vessel Occlusion: Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Bartosz Karaszewski ◽  
Adam Wyszomirski ◽  
Bartosz Jabłoński ◽  
David J. Werring ◽  
Dominika Tomaka
Keyword(s):  
Clinical Trials ◽  
Ischemic Stroke ◽  
Randomized Clinical Trials ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
Efficacy And Safety ◽  
Eligibility Criteria ◽  
Vessel Occlusion ◽  
Excellent Outcome ◽  
Symptomatic Intracerebral Hemorrhage

AbstractIntravenous recombinant tissue plasminogen activator (iv-rtPA) has been routinely used to treat ischemic stroke for 25 years, following large clinical trials. However, there are few prospective studies on the efficacy and safety of this therapy in strokes attributed to cerebral small vessel disease (SVD). We evaluated functional outcome (modified Rankin scale, mRS) and symptomatic intracerebral hemorrhage (sICH) using all available data on the effects of iv-rtPA in SVD-related ischemic stroke (defined either using neuroimaging, clinical features, or both). Using fixed-effect and random-effects models, we calculated the pooled effect estimates with regard to excellent and favorable outcomes (mRS=0–1 and 0–2 respectively, at 3 months), and the rate of sICH. Twenty-three studies fulfilled the eligibility criteria, 11 of which were comparative, and there were only 3 randomized clinical trials. In adjusted analyses, there was an increased odds of excellent outcome (adjusted OR=1.53, 95% CI: 1.29–1.82, I2: 0%) or favorable outcome (adjusted OR=1.68, 95% CI: 1.31–2.15,I2: 0%) in patients who received iv-rtPA compared with placebo. Across the six studies which reported it, the incidence of sICH was higher in the treatment group (M-H RR = 8.83, 95% CI: 2.76–28.27). The pooled rate of sICH in patients with SVD administered iv-rtPA was only 0.72% (95% CI: 0.12%–1.64%). We conclude that when ischemic stroke attributed to SVD is considered separately, available data on the effects of iv-rtPA therapy are insufficient for the highest level of recommendation, but it seems to be safe. Although further therapeutic trials in SVD-related ischemic stroke appear to be justified, our findings should not prevent its continued use for this group of patients in clinical practice.

scholarly journals Translational approaches to understanding metabolic dysfunction and cardiovascular consequences of obstructive sleep apnea

2015 ◽  
Vol 309 (7) ◽  
pp. H1101-H1111 ◽  
Author(s):  
Luciano F. Drager ◽  
Vsevolod Y. Polotsky ◽  
Christopher P. O'Donnell ◽  
Sergio L. Cravo ◽  
Geraldo Lorenzi-Filho ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Cardiovascular Risk ◽  
Sleep Apnea ◽  
Animal Models ◽  
Metabolic Dysfunction ◽  
Significant Progress ◽  
Glucose And Lipid Metabolism ◽  
Obstructive Sleep ◽  
Underlying Mechanisms ◽  
Made In

Obstructive sleep apnea (OSA) is known to be independently associated with several cardiovascular diseases including hypertension, myocardial infarction, and stroke. To determine how OSA can increase cardiovascular risk, animal models have been developed to explore the underlying mechanisms and the cellular and end-organ targets of the predominant pathophysiological disturbance in OSA–intermittent hypoxia. Despite several limitations in translating data from animal models to the clinical arena, significant progress has been made in our understanding of how OSA confers increased cardiovascular risk. It is clear now that the hypoxic stress associated with OSA can elicit a broad spectrum of pathological systemic events including sympathetic activation, systemic inflammation, impaired glucose and lipid metabolism, and endothelial dysfunction, among others. This review provides an update of the basic, clinical, and translational advances in our understanding of the metabolic dysfunction and cardiovascular consequences of OSA and highlights the most recent findings and perspectives in the field.

scholarly journals Green Tea and Epigallocatechin Gallate (EGCG) for the Management of Nonalcoholic Fatty Liver Diseases (NAFLD): Insights into the Role of Oxidative Stress and Antioxidant Mechanism

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1076
Author(s):  
Guoyi Tang ◽  
Yu Xu ◽  
Cheng Zhang ◽  
Ning Wang ◽  
Huabin Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Liver ◽  
Green Tea ◽  
Liver Diseases ◽  
Randomized Clinical Trials ◽  
Epigallocatechin Gallate ◽  
Protective Effects ◽  
Nonalcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver Diseases ◽  
Underlying Mechanisms

Nonalcoholic fatty liver diseases (NAFLD) represent a set of liver disorders progressing from steatosis to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma, which induce huge burden to human health. Many pathophysiological factors are considered to influence NAFLD in a parallel pattern, involving insulin resistance, oxidative stress, lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, inflammatory cascades, fibrogenic reaction, etc. However, the underlying mechanisms, including those that induce NAFLD development, have not been fully understood. Specifically, oxidative stress, mainly mediated by excessive accumulation of reactive oxygen species, has participated in the multiple NAFLD-related signaling by serving as an accelerator. Ameliorating oxidative stress and maintaining redox homeostasis may be a promising approach for the management of NAFLD. Green tea is one of the most important dietary resources of natural antioxidants, above which epigallocatechin gallate (EGCG) notably contributes to its antioxidative action. Accumulative evidence from randomized clinical trials, systematic reviews, and meta-analysis has revealed the beneficial functions of green tea and EGCG in preventing and managing NAFLD, with acceptable safety in the patients. Abundant animal and cellular studies have demonstrated that green tea and EGCG may protect against NAFLD initiation and development by alleviating oxidative stress and the related metabolism dysfunction, inflammation, fibrosis, and tumorigenesis. The targeted signaling pathways may include, but are not limited to, NRF2, AMPK, SIRT1, NF-κB, TLR4/MYD88, TGF-β/SMAD, and PI3K/Akt/FoxO1, etc. In this review, we thoroughly discuss the oxidative stress-related mechanisms involved in NAFLD development, as well as summarize the protective effects and underlying mechanisms of green tea and EGCG against NAFLD.

scholarly journals Circulating HIV DNA Correlates With Neurocognitive Impairment in Older HIV-infected Adults on Suppressive ART

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Michelli Faria de Oliveira ◽  
Ben Murrell ◽  
Josué Pérez-Santiago ◽  
Milenka Vargas ◽  
Ronald J. Ellis ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Neurocognitive Impairment ◽  
Neurocognitive Functioning ◽  
Neurocognitive Disorder ◽  
Prevention Strategies ◽  
Hiv Dna ◽  
Treatment And Prevention ◽  
Markers Of Inflammation ◽  
Underlying Mechanisms ◽  
Dna Reservoir

Abstract Older HIV-infected adults have a higher risk of neurocognitive impairment, but the underlying mechanisms are poorly understood. Here, we investigated the associations between levels of HIV DNA in peripheral blood, soluble markers of inflammation and cellular trafficking in blood and cerebrospinal fluid (CSF) and neurocognitive functioning among 18 younger (22–40 years) and 26 older (50–71 years) HIV-infected subjects, who were administered a comprehensive neurocognitive battery. Older HIV-infected individuals presented higher levels of inflammation in CSF and blood compared to younger individuals, but no difference was observed in HIV DNA levels. Among older participants, higher HIV DNA levels were significantly associated with more severe neurocognitive impairment (p = 0.005), particularly in the Executive Functions domain (p = 0.004). No association was observed between HIV DNA and neurocognition among younger individuals. Despite significantly increased inflammation observed in the older group, none of the inflammatory markers were associated with neurocognitive impairment among older HIV+ individuals (p > 0.05). Our study supports the involvement of peripheral HIV DNA reservoir in the pathogenesis of neurocognitive disorder during suppressive ART. Correlates of neurocognitive impairment might differ between younger and older adults, suggesting that future treatment and prevention strategies for HIV-associated neurocognitive disorders likely need to be tailored based on age.

Sign in / Sign up

Export Citation Format

Share Document