scholarly journals Platelet-Reactive Antibodies in Patients after Ischaemic Stroke—An Epiphenomenon or a Natural Protective Mechanism

2020 ◽  
Vol 21 (21) ◽  
pp. 8398
Author(s):  
Young Eun Park ◽  
Rushi Penumarthy ◽  
Paul P. Sun ◽  
Caroline Y. Kang ◽  
Marie-Christine Morel-Kopp ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Thrombus Formation ◽  
National Institutes Of Health ◽  
Neurological Dysfunction ◽  
Protective Mechanism ◽  
Stroke Patients ◽  
Neuroprotective Effects ◽  
Platelet Antibodies ◽  
Ischaemic Brain ◽  
Ischaemic Brain Damage

Ischaemic brain damage induces autoimmune responses, including the production of autoantibodies with potential neuroprotective effects. Platelets share unexplained similarities with neurons, and the formation of anti-platelet antibodies has been documented in neurological disorders. The aim of this study was to investigate the presence of anti-platelet antibodies in the peripheral blood of patients after ischaemic stroke and determine any clinical correlations. Using a flow cytometry-based platelet immunofluorescence method, we detected platelet-reactive antibodies in 15 of 48 (31%) stroke patients and two of 50 (4%) controls (p < 0.001). Western blotting revealed heterogeneous reactivities with platelet proteins, some of which overlapped with brain proteins. Stroke patients who carried anti-platelet antibodies presented with larger infarcts and more severe neurological dysfunction, which manifested as higher scores on the National Institutes of Health Stroke Scale (NIHSS; p = 0.009), but they had a greater recovery in the NIHSS by the time of hospital discharge (day 7 ± 2) compared with antibody-negative patients (p = 0.043). Antibodies from stroke sera reacted more strongly with activated platelets (p = 0.031) and inhibited platelet aggregation by up to 30.1 ± 2.8% (p < 0.001), suggesting the potential to interfere with thrombus formation. In conclusion, platelet-reactive antibodies can be found in patients soon after ischaemic stroke and correlate with better short-term outcomes, suggesting a potential novel mechanism limiting thrombosis.

scholarly journals Cold stress protein RBM3 responds to hypothermia and is associated with good stroke outcome

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Paulo Ávila-Gómez ◽  
Alba Vieites-Prado ◽  
Antonio Dopico-López ◽  
Saima Bashir ◽  
Héctor Fernández-Susavila ◽  
...  
Keyword(s):  
Body Temperature ◽  
Molecular Marker ◽  
Ischaemic Stroke ◽  
Rna Binding ◽  
Stress Protein ◽  
Brain Regions ◽  
Phase Iii ◽  
Binding Motif ◽  
Stroke Patients ◽  
Ischaemic Brain

Abstract RNA-binding motif protein 3 is a molecular marker of hypothermia that has proved neuroprotective in neurodegenerative disease models. However, its relationship to the well-recognized therapeutic effect of hypothermia in ischaemic stroke had not been studied. In this work, the expression of RNA-binding motif protein 3 was investigated in ischaemic animal models subjected to systemic and focal brain hypothermia, specifically the effects of RNA-binding motif protein 3 silencing and overexpression on ischaemic lesions. Moreover, the association of RNA-binding motif protein 3 levels with body temperature and clinical outcome was evaluated in two independent cohorts of acute ischaemic stroke patients (n = 215); these levels were also determined in a third cohort of 31 patients derived from the phase III EuroHYP-1 trial of therapeutic cooling in ischaemic stroke. The preclinical data confirmed the increase of brain RNA-binding motif protein 3 levels in ischaemic animals subjected to systemic and focal hypothermia; this increase was selectively higher in the cooled hemisphere of animals undergoing focal brain hypothermia, thus confirming the direct effect of hypothermia on RNA-binding motif protein 3 expression, while RNA-binding motif protein 3 up-regulation in ischaemic brain regions led to functional recovery. Clinically, patients with body temperature &lt;37.5°C in the first two cohorts had higher RNA-binding motif protein 3 values at 24 h and good outcome at 3 months post-ischaemic stroke, while RNA-binding motif protein 3 levels in the cooled third cohort tended to exceed those in placebo-treated patients. These results make RNA-binding motif protein 3 a molecular marker associated with the effect of hypothermia in ischaemic stroke and suggest its potential application as a promising protective target.

1,8-cineole ameliorates ischaemic brain damage via TRPC6/CREB pathways in rats

2021 ◽  
Author(s):  
Chen Meng ◽  
Wenjing Zeng ◽  
Jing Lv ◽  
Yu Wang ◽  
Meiling Gao ◽  
...  
Keyword(s):  
Brain Damage ◽  
Transient Receptor Potential ◽  
Infarct Volume ◽  
Glucose Deprivation ◽  
Neurological Dysfunction ◽  
Male Rats ◽  
Neuroprotective Effects ◽  
Ischaemic Brain

Abstract Objectives A previous in vitro study reported that the monoterpene oxide 1,8-cineole (cineole) attenuates neuronal caused by oxygen–glucose deprivation/reoxygenation in culture. However, to date, there is no in vivo evidence showing neuroprotective effects of cineole against stroke. This study aimed to investigate whether cineole attenuates cerebral ischaemic damage in rats. Methods A rat model of middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion was applied. Male rats were treated with oral cineole (100 mg/kg) for 7 consecutive days, then subjected to MCAO surgery. Infarct volume, neurologic deficits, apoptosis and expression levels of all-spectrin breakdown products of 145 kDa (SBDP145), transient receptor potential canonical (subtype) 6 (TRPC6) and phosphorylated CREB (p-CREB) were measured in ischaemic brain tissues. Key findings Cineole treatment significantly reduced infarct volume, neurological dysfunction, neuronal apoptosis, SBDP145 formation and TRPC6 degradation and enhanced p-CREB expression in MCAO rats compared with vehicle treatment. These neuroprotective effects were markedly suppressed by pharmacological inhibition of MEK or CaMKIV signalling. Conclusions Our study provides in vivo evidence demonstrating that cineole pretreatment attenuates ischaemic stroke-induced brain damage, mainly through blocking calpain-induced TRPC6 degradation and activating CREB via MEK/CREB and CaMKIV/CREB signalling pathways.

Serine proteases of the complement lectin pathway and their genetic variations in ischaemic stroke

2017 ◽  
Vol 71 (2) ◽  
pp. 141-147 ◽  
Author(s):  
Gohar Tsakanova ◽  
Ani Stepanyan ◽  
Karen Nahapetyan ◽  
Robert B Sim ◽  
Arsen Arakelyan ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Genetic Polymorphisms ◽  
Serine Proteases ◽  
Healthy Subjects ◽  
Lectin Pathway ◽  
Nucleotide Polymorphisms ◽  
Ischaemic Brain ◽  
Proteolytic Activities ◽  
Ischaemic Brain Damage ◽  
Armenian Population

AimsThe aim of the current study was to assess the proteolytic activities of collectin-bound MASP-1 and MASP-2 in the blood of patients with ischaemic stroke, as well as the association of their six genetic polymorphisms (rs3203210, rs28945070, rs28945073 in MASP1 gene and rs2273343, rs12711521, rs147270785 in MASP2 gene) with this pathology.MethodsIn total, 250 patients and 300 healthy subjects were involved in this study. MBL-associated serine protease (MASP)-1 and MASP-2 activities were measured using in-house developed immunofluorescent and enzyme-linked immunosorbent assays, respectively. Sequence specific primer PCR was used to study the association of MASP1 and MASP2 genetic polymorphisms with ischaemic stroke.ResultsThe results obtained demonstrate that the activities of collectin-bound MASP-1 and MASP-2 in patients with ischaemic stroke are significantly higher than those in healthy subjects (p<0.001). According to the data obtained for genotyping, the rs3203210 polymorphism in the MASP1 gene and the rs147270785 polymorphism in the MASP2 gene are associated with ischaemic stroke (p<0.0001).ConclusionsIn conclusion we suggest that the complement lectin pathway serine proteases, MASP-1 and MASP-2, can be associated with ischaemic stroke development risk and may participate in pathological events leading to post-ischaemic brain damage. Moreover rs3203210 and rs147270785 single nucleotide polymorphisms in the MASP1 and MASP2 genes, respectively, are strongly associated with ischaemic stroke, and the minor rs3203210*C and rs147270785*A alleles of these polymorphisms may be considered as protective factors for ischameic stroke, at least in the Armenian population.

Is Reperfusion Useful in Ischaemic Stroke Patients Presenting with a Low National Institutes of Health Stroke Scale and a Proximal Large Vessel Occlusion of the Anterior Circulation?

2017 ◽  
Vol 43 (5-6) ◽  
pp. 305-312 ◽  
Author(s):  
Cyril Dargazanli ◽  
Arturo Consoli ◽  
Benjamin Gory ◽  
Raphaël Blanc ◽  
Julien Labreuche ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Favourable Outcome ◽  
National Institutes Of Health ◽  
Large Vessel Occlusion ◽  
Stroke Patients ◽  
Anterior Circulation ◽  
Vessel Occlusion ◽  
Excellent Outcome ◽  
Mild Stroke ◽  
The Impact

Background: In population-based studies, patients presenting with minor or mild stroke symptoms represent about two-thirds of stroke patients, and almost one-third of these patients are unable to ambulate independently at the time of discharge. Although mechanical thrombectomy (MT) has become the standard of care for acute ischaemic stroke with proximal large vessel occlusion (LVO) in the anterior circulation, the management of patients harbouring proximal occlusion and minor-to-mild stroke symptoms has not yet been determined by recent trials. The purpose of this study was to evaluate the impact of reperfusion on clinical outcome in low National Institutes of Health Stroke Scale (NIHSS) patients treated with MT. Methods: We analysed 138 consecutive patients with acute LVO of the anterior circulation (middle cerebral artery M1 or M2 segment, internal carotid artery or tandem occlusion) with NIHSS <8, having undergone MT in 3 different centres. Reperfusion was graded using the modified thrombolysis in cerebral infarction (TICI) score and 3 grades were defined, ranging from failed or poor reperfusion (TICI 0, 1, 2A) to complete reperfusion (TICI 3). The primary clinical endpoint was an excellent outcome defined as a modified Rankin score (mRs) 0-1 at 3-months. The impact of reperfusion grade was assessed in univariate and multivariate analyses. The secondary endpoints included favourable functional outcome (90-day mRS 0-2), death and safety concerns. Results: Successful reperfusion was achieved in 81.2% of patients (TICI 2B, n = 47; TICI 3, n = 65). Excellent outcome (mRs 0-1) was achieved in 69 patients (65.0%) and favourable outcome (mRs ≤2) in 108 (78.3%). Death occurred in 7 (5.1%). Excellent outcome increased with reperfusion grades, with a rate of 34.6% in patients with failed/poor reperfusion, 61.7% in patients with TICI 2B reperfusion, and 78.5% in patients with TICI 3 reperfusion (p < 0.001). In multivariate analysis adjusted for patient characteristics associated with excellent outcome, the reperfusion grade remained significantly associated with an increase in excellent outcome; the OR (95% CI) was 3.09 (1.06-9.03) for TICI 2B and 6.66 (2.27-19.48) for TICI 3, using the failed/poor reperfusion grade as reference. Similar results were found regarding favourable outcome (90-day mRs 0-2) or overall mRS distribution (shift analysis). Conclusion: Successful reperfusion is strongly associated with better functional outcome among patients with proximal LVO in the anterior circulation and minor-to-mild stroke symptoms. Randomized controlled studies are mandatory to assess the benefit of MT compared with optimal medical management in this subset of patients.

Pre-Admission CHADS2 and CHA2DS2-VASc Scores on Early Neurological Worsening

2021 ◽  
pp. 1-8
Author(s):  
Ki-Woong Nam ◽  
Chi Kyung Kim ◽  
Sungwook Yu ◽  
Jong-Won Chung ◽  
Oh Young Bang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Stroke Risk ◽  
Multivariable Analysis ◽  
National Institutes Of Health ◽  
Risk Scores ◽  
Stroke Patients ◽  
Nihss Score ◽  
Early Neurological Deterioration ◽  
Close Relationship ◽  
The Relationship

<b><i>Background:</i></b> Stroke risk scores (CHADS<sub>2</sub> and CHA<sub>2</sub>DS<sub>2</sub>-VASc) not only predict the risk of stroke in atrial fibrillation (AF) patients, but have also been associated with prognosis after stroke. <b><i>Objective:</i></b> The aim of this study was to evaluate the relationship between stroke risk scores and early neurological deterioration (END) in ischemic stroke patients with AF. <b><i>Methods:</i></b> We included consecutive ischemic stroke patients with AF admitted between January 2013 and December 2015. CHADS<sub>2</sub> and CHA<sub>2</sub>DS<sub>2</sub>-VASc scores were calculated using the established scoring system. END was defined as an increase ≥2 on the total National Institutes of Health Stroke Scale (NIHSS) score or ≥1 on the motor NIHSS score within the first 72 h of admission. <b><i>Results:</i></b> A total of 2,099 ischemic stroke patients with AF were included. In multivariable analysis, CHA<sub>2</sub>DS<sub>2</sub>-VASc score (adjusted odds ratio [aOR] = 1.17, 95% confidence interval [CI] = 1.04–1.31) was significantly associated with END after adjusting for confounders. Initial NIHSS score, use of anticoagulants, and intracranial atherosclerosis (ICAS) were also found to be closely associated with END, independent of the CHA<sub>2</sub>DS<sub>2</sub>-VASc score. Multivariable analysis stratified by the presence of ICAS demonstrated that both CHA<sub>2</sub>DS<sub>2</sub>-VASc (aOR = 1.20, 95% CI = 1.04–1.38) and CHADS<sub>2</sub> scores (aOR = 1.24, 95% CI = 1.01–1.52) were closely related to END in only patients with ICAS. In patients without ICAS, neither of the risk scores were associated with END. <b><i>Conclusions:</i></b> High CHA<sub>2</sub>DS<sub>2</sub>-VASc score was associated with END in ischemic stroke patients with AF. This close relationship is more pronounced in patients with ICAS.

Is a picture-perfect thrombectomy necessary in acute ischemic stroke?

2021 ◽  
pp. neurintsurg-2020-017193
Author(s):  
Ching-Jen Chen ◽  
Reda Chalhoub ◽  
Dale Ding ◽  
Jeyan S Kumar ◽  
Natasha Ironside ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Mechanical Thrombectomy ◽  
National Institutes Of Health ◽  
Stroke Patients ◽  
Anterior Circulation ◽  
Vessel Occlusion ◽  
Symptomatic Intracerebral Hemorrhage ◽  
History Of ◽  
Multivariable Models ◽  
Secondary Outcomes

BackgroundThe benefit of complete reperfusion (modified Thrombolysis in Cerebral Infarction (mTICI) 3) over near-complete reperfusion (≥90%, mTICI 2c) remains unclear. The goal of this study is to compare clinical outcomes between mechanical thrombectomy (MT)-treated stroke patients with mTICI 2c versus 3.MethodsThis is a retrospective study from the Stroke Thrombectomy and Aneurysm Registry (STAR) comprising 33 centers. Adults with anterior circulation arterial vessel occlusion who underwent MT yielding mTICI 2c or mTICI 3 reperfusion were included. Patients were categorized based on reperfusion grade achieved. Primary outcome was modified Rankin Scale (mRS) 0–2 at 90 days. Secondary outcomes were mRS scores at discharge and 90 days, National Institutes of Health Stroke Scale score at discharge, procedure-related complications, and symptomatic intracerebral hemorrhage.ResultsThe unmatched mTICI 2c and mTICI 3 cohorts comprised 519 and 1923 patients, respectively. There was no difference in primary (42.4% vs 45.1%; p=0.264) or secondary outcomes between the unmatched cohorts. Reperfusion status (mTICI 2c vs 3) was also not predictive of the primary outcome in non-imputed and imputed multivariable models. The matched cohorts each comprised 191 patients. Primary (39.8% vs 47.6%; p=0.122) and secondary outcomes were also similar between the matched cohorts, except the 90-day mRS which was lower in the matched mTICI 3 cohort (p=0.049). There were increased odds of the primary outcome with mTICI 3 in patients with baseline mRS ≥2 (36% vs 7.7%; p=0.011; pinteraction=0.014) and a history of stroke (42.3% vs 15.4%; p=0.027; pinteraction=0.041).ConclusionsComplete and near-complete reperfusion after MT appear to confer comparable outcomes in patients with acute stroke.

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