scholarly journals Beyond the Brain: The Systemic Pathophysiological Response to Acute Ischemic Stroke

2020 ◽  
Vol 22 (2) ◽  
pp. 159-172
Author(s):  
Maria H.H. Balch ◽  
Shahid M. Nimjee ◽  
Cameron Rink ◽  
Yousef Hannawi
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Systemic Disease ◽  
Glucose Deprivation ◽  
Future Research ◽  
Ischemic Brain ◽  
Excitatory Neurotransmitter ◽  
Stroke Research ◽  
Bidirectional Interactions ◽  
The Brain

Stroke research has traditionally focused on the cerebral processes following ischemic brain injury, where oxygen and glucose deprivation incite prolonged activation of excitatory neurotransmitter receptors, intracellular calcium accumulation, inflammation, reactive oxygen species proliferation, and ultimately neuronal death. A recent growing body of evidence, however, points to far-reaching pathophysiological consequences of acute ischemic stroke. Shortly after stroke onset, peripheral immunodepression in conjunction with hyperstimulation of autonomic and neuroendocrine pathways and motor pathway impairment result in dysfunction of the respiratory, urinary, cardiovascular, gastrointestinal, musculoskeletal, and endocrine systems. These end organ abnormalities play a major role in the morbidity and mortality of acute ischemic stroke. Using a pathophysiology-based approach, this current review discusses the pathophysiological mechanisms following ischemic brain insult that result in end organ dysfunction. By characterizing stroke as a systemic disease, future research must consider bidirectional interactions between the brain and peripheral organs to inform treatment paradigms and develop effective, comprehensive therapeutics for acute ischemic stroke.

Abstract MP16: Excessive White Matter Hyperintensity Burden and Functional Outcomes After Acute Ischemic Stroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Sungmin Hong ◽  
Anne-katrin Giese ◽  
Markus D Schirmer ◽  
Adrian V Dalca ◽  
Anna Bonkhoff ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Acute Ischemic Stroke ◽  
Functional Outcomes ◽  
Life Time ◽  
Stroke Recovery ◽  
White Matter Hyperintensity ◽  
Brain Health ◽  
Stroke Outcomes ◽  
The Brain

Objective: Ability of the brain to recover after an acute ischemic stroke (AIS) is linked to the pre-stroke burden of white matter hyperintensity (WMH), a radiographic marker of brain health. We sought to determine the excessive WMH burden in an AIS population and investigate its association with 3-month stroke outcomes. Data: We used 2,435 subjects from the MRI-GENIE study. Three-month functional outcomes of 872 subjects among those subjects were measured by 90-day modified Ranking Scale (mRS). Methods: We automatically quantified WMH volume (WMHv) on FLAIR images and adjusted for a brain volume. We modeled a trend using the factor analysis (FA) log-linear regression using age, sex, atrial fibrillation, diabetes, hypertension, coronary artery disease and smoking as input variables. We categorized three WMH burden groups based on the conditional probability given by the model (LOW: lower 33%, MED: middle 34%, and HIGH: upper 33%). The subgroups were compared with respect to mRS (median and dichotomized odds ratio (OR) (good/poor: mRS 0-2/3-6)). Results: Five FA components out of seven with significant relationship to WMHv (p<0.001) were used for the regression modeling (R 2 =0.359). The HIGH group showed higher median (median=2, IQR=2) mRS score than LOW (median=1, IQR=1) and MED (median=1, IQR=1). The odds (OR) of good AIS outcome for LOW and MED were 1.8 (p=0.0001) and 1.6 (p=0.006) times higher than HIGH, respectively. Conclusion: Once accounted for clinical covariates, the excessive WMHv was associated with worse 3-month stroke outcomes. These data suggest that a life-time of injury to the white matter reflected in WMH is an important factor for stroke recovery and an indicator of the brain health.

scholarly journals Non-Coding RNA in Acute Ischemic Stroke: Mechanisms, Biomarkers and Therapeutic Targets

2018 ◽  
Vol 27 (12) ◽  
pp. 1763-1777 ◽  
Author(s):  
Sheng-Wen Wang ◽  
Zhong Liu ◽  
Zhong-Song Shi
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Neural Development ◽  
Therapeutic Targets ◽  
Circular Rnas ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Cerebral Ischemic ◽  
Functional Rnas ◽  
The Brain

Non-coding RNAs (ncRNAs) are a class of functional RNAs that regulate gene expression in a post-transcriptional manner. NcRNAs include microRNAs, long non-coding RNAs and circular RNAs. They are highly expressed in the brain and are involved in the regulation of physiological and pathophysiological processes, including cerebral ischemic injury, neurodegeneration, neural development, and plasticity. Stroke is one of the leading causes of death and physical disability worldwide. Acute ischemic stroke (AIS) occurs when brain blood flow stops, and that stoppage results in reduced oxygen and glucose supply to cells in the brain. In this article, we review the latest progress on ncRNAs in relation to their implications in AIS, as well as their potential as diagnostic and prognostic biomarkers. We also review ncRNAs acting as possible therapeutic targets in future precision medicine. Finally, we conclude with a brief discussion of current challenges and future directions for ncRNAs studies in AIS, which may facilitate the translation of ncRNAs research into clinical practice to improve clinical outcome of AIS.

scholarly journals Histological stroke clot analysis after thrombectomy: Technical aspects and recommendations

2019 ◽  
Vol 15 (5) ◽  
pp. 467-476 ◽  
Author(s):  
S Staessens ◽  
S Fitzgerald ◽  
T Andersson ◽  
F Clarençon ◽  
F Denorme ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Endovascular Procedures ◽  
Cerebral Arteries ◽  
Research Field ◽  
Stroke Therapy ◽  
Technical Aspects ◽  
Stroke Research

The recent advent of endovascular procedures has created the unique opportunity to collect and analyze thrombi removed from cerebral arteries, instigating a novel subfield in stroke research. Insights into thrombus characteristics and composition could play an important role in ongoing efforts to improve acute ischemic stroke therapy. An increasing number of centers are collecting stroke thrombi. This paper aims at providing guiding information on thrombus handling, procedures, and analysis in order to facilitate and standardize this emerging research field.

Management of acute ischemic stroke

BMJ ◽  
2020 ◽  
pp. l6983 ◽  
Author(s):  
Michael S Phipps ◽  
Carolyn A Cronin
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Treatment Time ◽  
Recurrent Stroke ◽  
Time Windows ◽  
Intravenous Thrombolysis ◽  
Stroke Care ◽  
Developed Countries ◽  
Future Research ◽  
The Impact

ABSTRACT Stroke is the leading cause of long term disability in developed countries and one of the top causes of mortality worldwide. The past decade has seen substantial advances in the diagnostic and treatment options available to minimize the impact of acute ischemic stroke. The key first step in stroke care is early identification of patients with stroke and triage to centers capable of delivering the appropriate treatment, as fast as possible. Here, we review the data supporting pre-hospital and emergency stroke care, including use of emergency medical services protocols for identification of patients with stroke, intravenous thrombolysis in acute ischemic stroke including updates to recommended patient eligibility criteria and treatment time windows, and advanced imaging techniques with automated interpretation to identify patients with large areas of brain at risk but without large completed infarcts who are likely to benefit from endovascular thrombectomy in extended time windows from symptom onset. We also review protocols for management of patient physiologic parameters to minimize infarct volumes and recent updates in secondary prevention recommendations including short term use of dual antiplatelet therapy to prevent recurrent stroke in the high risk period immediately after stroke. Finally, we discuss emerging therapies and questions for future research.

scholarly journals Endogenous THBD (Thrombomodulin) Mediates Angiogenesis in the Ischemic Brain—Brief Report

2020 ◽  
Vol 40 (12) ◽  
pp. 2837-2844 ◽  
Author(s):  
Jan Wenzel ◽  
Dimitrios Spyropoulos ◽  
Julian Christopher Assmann ◽  
Mahtab Ahmad Khan ◽  
Ines Stölting ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Soluble Form ◽  
Stroke Outcome ◽  
Brain Endothelial Cells ◽  
Ischemic Brain ◽  
Infarct Area ◽  
The Brain

Objective: THBD (thrombomodulin) is part of the anticoagulant protein C-system that acts at the endothelium and is involved in anti-inflammatory and barrier-stabilizing processes. A recombinant soluble form of THBD was shown to have protective effects in different organs, but how the endogenous THBD is regulated during ischemia, particularly in the brain is not known to date. The aim of this study was to investigate the role of THBD, especially in brain endothelial cells, during ischemic stroke. Approach and Results: To induce ischemic brain damage, we occluded the middle cerebral artery of mice. We found an increased endothelial expression of Thbd in the peri-infarct area, whereas in the core of the ischemic tissue Thbd expression was decreased compared with the contralateral side. We generated a novel Cre/loxP-based mouse line that allows for the inducible deletion of Thbd specifically in brain endothelial cells, which worsened stroke outcome 48 hours after middle cerebral artery occlusion. Unexpectedly, we found no signs of increased coagulation, thrombosis, or inflammation in the brain but decreased vessel diameters and impaired angiogenesis in the peri-infarct area that led to a reduced overall vessel length 1 week after stroke induction. Conclusions: Endogenous THBD acts as a protective factor in the brain during ischemic stroke and enhances vessel diameter and proliferation. These previously unknown properties of THBD could offer new opportunities to affect vessel function after ischemia and thereby improve stroke outcome.

scholarly journals Lillian Mary Pickford. 14 August 1902—14 August 2002

2019 ◽  
Vol 67 ◽  
pp. 371-400
Author(s):  
John F. B. Morrison ◽  
John A. Russell
Keyword(s):  
Hot Flashes ◽  
Fluid Composition ◽  
Posterior Pituitary ◽  
Excitatory Neurotransmitter ◽  
Female Sex Hormones ◽  
Concentrate Urine ◽  
Posterior Pituitary Gland ◽  
Bidirectional Interactions ◽  
The Brain ◽  
Mary Pickford

Mary Pickford was an experimental physiologist who carried out pioneering work on the actions of the hormones (oxytocin and vasopressin [ syn. antidiuretic hormone, ADH]) secreted by the posterior pituitary gland, which is part of the brain. She provided understanding of how the secretion of these hormones is controlled to regulate body fluid composition, specifically the maintenance, through actions on the kidneys, of normal osmolarity and Na + concentration, and hence blood volume and pressure. Using the water-loaded dog model she showed that vasopressin is the only hormone that regulates the excretion of water, by stimulating the kidneys to concentrate urine; she found that oxytocin could stimulate excretion of Na + . She showed that acetylcholine is an excitatory neurotransmitter in the hypothalamus, stimulating the neurons that produce vasopressin to secrete—the first evidence for acetylcholine action in the brain. The principles that Mary established have been extensively confirmed; hence, she was important in the establishment of the concepts and discipline of neuroendocrinology, which is about the bidirectional interactions between hormones and the brain. Using human and animal models, in her later work Mary focused on possible roles of interactions between female sex hormones and vasodilating actions of oxytocin in the perimenopausal problem of ‘hot flashes’ (or ‘hot flushes’) experienced by many women. She faced, but overcame, entrenched gender prejudice during her career; she was the first woman to be elected to the Pharmacological Society, and the first woman appointed to a chair in the Edinburgh Medical School.

Remote ischemic conditioning for acute ischemic stroke: dawn in the darkness

2016 ◽  
Vol 27 (5) ◽  
pp. 501-510 ◽  
Author(s):  
Jingrui Pan ◽  
Xiangpen Li ◽  
Ying Peng
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Ischemic Preconditioning ◽  
Research Progress ◽  
High Morbidity ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Remote Ischemic Perconditioning ◽  
Neuroprotective Strategy ◽  
The Brain

AbstractStroke is a leading cause of disability with high morbidity and mortality worldwide. Of all strokes, 87% are ischemic. The only approved treatments for acute ischemic stroke are intravenous thrombolysis with alteplase within 4.5 h and thrombectomy within 8 h after symptom onset, which can be applied to just a few patients. During the past decades, ischemic preconditioning has been widely studied to confirm its neuroprotection against subsequent ischemia/reperfusion injury in the brain, including preconditioning in situ or in a remote organ (such as a limb) before onset of brain ischemia, the latter of which is termed as remote ischemic preconditioning. Because acute stroke is unpredicted, ischemic preconditioning is actually not suitable for clinical application. So remote ischemic conditioning performed during or after the ischemic duration of the brain was then designed to study its neuroprotection alone or in combination with alteplase in animals and patients, which is named as remote ischemic perconditioning or remote ischemic postconditioning. As expected, animal experiments and clinical trials both showed exciting results, indicating that an evolution in the treatment for acute ischemic stroke may not be far away. However, some problems or disputes still exist. This review summarizes the research progress and unresolved issues of remote ischemic conditioning (pre-, per-, and post-conditioning) in treating acute ischemic stroke, with the hope of advancing our understanding of this promising neuroprotective strategy for ischemic stroke in the near future.

Protecting Oligodendrocytes by Targeting Non-Glutamate Receptors as a New Therapeutic Strategy for Ischemic Stroke

Pharmacology ◽  
2017 ◽  
Vol 100 (3-4) ◽  
pp. 148-152
Author(s):  
Pan Luo ◽  
Dong Liu ◽  
Lianjun Guo
Keyword(s):  
Ischemic Stroke ◽  
Glutamate Receptors ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Cellular Level ◽  
Transient Receptor Potential Channels ◽  
Excitatory Neurotransmitter ◽  
Cellular Targets ◽  
Potential Channels ◽  
The Brain

Ischemic stroke has many devastating effects within the brain. At the cellular level, excitotoxicity has been a popular pharmacological target for therapeutics. To date, many clinical trials have been performed with drugs that target excitatory neurotransmitter receptors, such as NMDA receptor agonists. The results, however, have been lackluster. Most efforts to understand the impacts of excitotoxicity on the brain have focused primarily on neurons, and to a lesser degree, on gliocytes as cellular targets. Recent evidence suggests that oligodendrocytes (OLGs), the myelin-forming cells in the central nervous system, are damaged by ischemia in a manner completely different from that in neurons. Whereas ischemia primarily damages neurons through overactivation of ionotropic glutamate receptors, the ischemia damage in OLGs occurs through overactivation of H+-gated transient receptor potential channels. Given the differential mechanisms of ischemic injury between neurons and OLGs, strategies to target non-glutamate receptors to prevent OLG damage/demyelination deserve greater attention in drug development. Such strategies, combined with neuroprotective measures, could provide an excellent therapeutic avenue for the treatment of ischemic stroke.

scholarly journals Use of heparinized saline flush during endovascular thrombectomy for acute ischemic stroke; a survey of clinical practice in the Netherlands

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Faysal Benali ◽  
Christiaan van der Leij ◽  
Julie Staals ◽  
Wim H. van Zwam
Keyword(s):  
Ischemic Stroke ◽  
Clinical Practice ◽  
The Netherlands ◽  
Research And Development ◽  
Acute Ischemic Stroke ◽  
Future Research ◽  
Heparin Dose ◽  
Endovascular Thrombectomy ◽  
Heparinized Saline ◽  
Relevant Variables

Abstract Background and introduction Information about optimal use of heparin in flush fluids during endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) is lacking. Variables that determine total heparin dose entering the patient by flush fluids are mostly unknown. We aim to provide insight in these unknown but highly relevant variables. Methods and results We performed a survey including all Dutch interventionists performing EVT (n = 79) collecting data on used concentration of heparin in infusion bags, number of infusion bags connected, timing of connecting the flush line and the dripping rate (ml/sec). We calculated potential heparin dose entering the patient per hour through flush fluids (IU/h). Twenty-eight interventionists (35%) representing 17 Dutch stroke centers completed the survey. Eight interventionists responded not to add any heparin to flush fluids (18%). The highest amount of heparin entering the patients was 13,500 IU/h, reported by 2 interventionists from the same center (4%). Conclusions We provide insight in the use of heparinized flush during EVT in the Netherlands. Total amounts of heparin administered via flush fluids may go up to 13,500 IU/h. With this paper we intend to set a starting for future research and development of guidelines on the use of heparinized flush fluids during EVT for AIS.

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