Days Of Ischemic Stroke Research Articles

Oral Health in Patients Hospitalized Because of Ischemic Stroke.

Background/Objectives: Maintenance of good oral health is relevant to overall health and quality of life. Results of many analyses showed that stroke patients had worse oral health than the control population. The aim of this study was a clinical assessment of oral condition in post-stroke patients and a healthy population. Methods: Oral health was assessed in stroke patients on the first day of ischemic stroke, and in a control group of healthy subjects. The number of teeth, the presence of active carious foci, fillings, and prosthetic restorations were evaluated. To assess oral hygiene, the Approximal Plaque Index (API) was used. In periodontal examinations, the presence of dental deposits, the depth of the existing periodontal pockets, tooth mobility, and the Sulcus Bleeding Index (SBI) during probing were assessed. Results: Significantly higher mean values of Decayed Teeth (DT), Missing Teeth (MT), and Decayed, Missing, and Filled Teeth (DMFT) indices were recorded in the study group. The incidence of dental caries, API, and SBI was also significantly higher in the study group. The study and control groups did not differ significantly in the average number of pockets 3 mm deep and deeper and in the frequency of having prosthetic restorations. Conclusions: Oral health and the level of oral hygiene in patients hospitalized because of ischemic stroke, in comparison with that in a healthy population, is not satisfactory. Active interdisciplinary collaboration between various medical specialists in the therapy of patients with general illnesses, including stroke, is strongly recommended.

Increased levels of platelet function-related miR-16-5p predicts increased severity of ischemic stroke: in silico validation analysis

Abstract Background Ischemic stroke (IS) is one of the most frequent causes of death. Since miRNAs have been illustrated to play an important role in various processes through regulation of multiple genes, and platelet function, their utility as novel biomarkers should be determined. We aimed to identify and validate circulating miRNAs, modulated in acute ischemic stroke (IS) patients in order to distinguish the most specific as biomarkers to facilitate diagnosis and prognosis. Method Sixty patients with acute IS (24-h and 7-days after IS) and 30 age- and gender-matched individuals free of stroke with multiple risk factors for cardiovascular disease. Studied miRNAs were selected based on bioinformatic analysis that was previously published by our team (1-2-3). PlasmaRNA was extracted; quality RNA was assessed: fluorometric assay; RT-PCR for miRNAs expression measurement p<0.05. Results Let-7e expression 7-day of IS was significantly lower than both controls and first day of IS (p=0.007, p=0.001, res). miR-125a-3p was lower both at day-1 and day-7 of IS compared to controls (p=0.008, p=0.020, res). miR-125a-5p on the other hand, had significantly higher expression at day-1 compared to controls (p=0.002). Both miR-125a-3p and -5p showed diagnostic value in ROC curve analysis (AUC= 0.705, AUC= 0.709, res). Patients with moderate stroke (based on NIHSS) had significantly higher miR-16-5p expression levels compared to patients with minor stroke at the first day of IS (AUC: 0.718, (95% CI, 0.59-0.85) p = 0.004). High baseline expression of miR-16-5p and diabetes mellitus are independent predictors of increased severity of stroke to a multivariate analysis (OR: 4.341; 95% CI, 1.15–16.42; p = 0.031 and OR: 4.653; 95% CI, 1.07–20.19; p = 0.040, res). Conclusion In this study we validated miRNAs based on our previous bioinformatic analysis which could serve as novel, platelet-related predictive biomarkers of the IS severity, and can be used for early stratification of patients and prediction of severity of disease development in an individual.

Serum Level of Brain-Derived Neurotrophic Factor and Thrombotic Type Are Predictive of Cognitive Impairment in the Acute Period of Ischemic Strokes Patients.

40-70% of patients after a stroke, including a mild one, may experience cognitive impairment. Brain-derived neurotrophic factor (BDNF) plays a significant role in the pathogenesis and rehabilitation of ischemic stroke and also affects the patients' recovery prognosis. An association between cognitive impairment in the poststroke period and lower peripheral BDNF levels is known, but the prognostic significance of serum BDNF levels and clinical characteristics for the risk of developing cognitive impairment in the acute period remains uncertain. We conducted a prospective cohort study of patients in the acute phase of ischemic stroke. Clinical examination, assessment of neurological status, neuropsychological testing, and laboratory analyzes were performed on patients at 1 and 14 days after ischemic stroke. The state of cognitive functions was assessed by the Mini-Mental State Examination scale. Quantification of BDNF in blood serum was performed by solid-phaseenzyme-linked immunosorbent assay (ELISA). We found that within 14 days after an acute ischemic stroke, we found a decrease in the clinical severity of patients compared to 1 day of the onset of the disease before the start of treatment and a significant decrease in the level of BDNF in the blood serum of patients with ischemic stroke both on the first and on the 14th day. However, during the 2 weeks of the acute period, no significant changes were detected, despite the general improvement of the clinical condition. In our study, cognitive impairment was found in almost half of the patients on the first day of ischemic stroke, and there was no significant reduction in this prevalence over 2 weeks. We found that a low level of BDNF and a thrombotic subtype of ischemic stroke can be risk factors for cognitive impairment in the acute period, which can be useful in planning treatment and rehabilitation measures.

Abstract 41: Synthesis And Pharmacological Validation Of Novel Neuroprotective Purinergic Receptor P2X4 Antagonists For The Treatment Of Ischemic Stroke

Background and Purpose: Identification of a novel treatment for ischemic stroke is urgently needed. We previously showed that genetic deletion as well as short term pharmacological inhibition of P2X4R, a purinergic receptor for adenosine triphosphate ATP, provides acute neuroprotection and thus can be potential drug targets to treat ischemic stroke. Here we synthesized and pharmacologically validated those experimental drugs for the treatment of ischemic stroke. Methods: We first performed the P2X4 receptor structure activity (SAR) relationship based on known heterocyclic antagonist P2X4 antagonists including NP-1815-PX Following extensive modification of the reported synthetic route, we synthesized several analogues that maintained or enhanced antagonist affinity. We used [Ca 2+ ] i influx assay in P2X4R overexpressing human HEK cells to identify potent and specific P2X4R antagonist. Two most potent leads (MRS4719 and 4596 given subcutaneously for 3 days post stroke) were then tested for their neuroprotective activity using middle cerebral artery occlusion (MCAo) model of ischemic stroke (60 min MCAo followed by 3 days of reperfusion) using both sexes of young and aged mice. MRS4719 was also tested in human primary monocyte derived macrophage obtained from the blood of de-identified aged healthy subjects (55±10 years). Results: Analogues MRS 4719 and MRS4596 were most potent at human (h) P2X4R (IC 50 0.503 and 1.38 μM, respectively), and were highly selective versus hP2X1R, hP2X2/3R, hP2X3R). Both MRS 4719 and MRS 4596 showed neuroprotective effects after 3 days of ischemic stroke in a dose dependent manner in young mice (8-12 weeks old). Optimal dose of MRS4719 (1.5 mg/kg/day) also significantly reduced infarct volume (59.6±5.3 vs. 27.47±10.23 mm 3 ; p<0.05) in middle-aged mice (11-12 months). MRS 4719 showed learning and memory enhancing activity when measured after 4 weeks of stroke. MRS 4719 inhibited ATP-induced [Ca 2+ ] i influx in primary human monocyte-derived macrophages, consistent with its blocking effect at endogenously expressed P2X4R. Conclusions: This study indicates MRS4719 is a potent P2X4R antagonist and has translational potential for the treating of ischemic stroke across the age.

Health Services Use and Outcomes for Hospital Admissions With a Major Cardiovascular Event Recorded in Health Care Administrative Data in Patients Receiving Maintenance Hemodialysis: A Retrospective Cohort Study.

Administrative data are used in studies of hemodialysis care to report cardiovascular-related hospitalizations. Showing recorded events are associated with significant health care resource use and poor outcomes would confirm that administrative data algorithms identify clinically meaningful events. The objective of this study was to describe the 30-day health service use and outcomes when a hospital admission with myocardial infarction, congestive heart failure, or ischemic stroke is recorded in administrative databases. This is a retrospective review of linked administrative data. Patients receiving maintenance in-center hemodialysis in Ontario, Canada, between April 1, 2013, and March 31, 2017, were included. Records from linked health care databases at ICES in Ontario, Canada were considered. We identified hospital admission with the most responsible diagnosis recorded as myocardial infarction, congestive heart failure, or ischemic stroke. We then assessed the frequency of common tests, procedures, consultations, post-discharge outpatient drug prescriptions, and outcomes within 30 days following the hospital admission. We used descriptive statistics to summarize results using counts and percentages for categorical variables and means with standard deviations or medians with quartile ranges for continuous variables. There were 14 368 patients who received maintenance hemodialysis between April 1, 2013, and March 31, 2017. The number of events per 1000 person-years was 33.5 for hospital admissions with myocardial infarction, 34.2 for congestive heart failure, and 12.9 for ischemic stroke. The median (25th, 75th percentile) duration of hospital stay was 5 (3-10) days for myocardial infarction, 4 (2-8) days for congestive heart failure, and 9 (4-18) days for ischemic stroke. The chance of death within 30 days was 21% for myocardial infarction, 11% for congestive heart failure, and 19% for ischemic stroke. Events, procedures, and tests recorded in administrative data can be misclassified compared with medical charts. In patients receiving maintenance hemodialysis, hospital admissions of major cardiovascular events routinely recorded in health administrative databases are associated with significant use of health service resources and poor health outcomes.

The direct and indirect effects of length of hospital stay on the costs of inpatients with stroke in Ningxia, China, between 2015 and 2020: A retrospective study using quantile regression and structural equation models.

ImportanceLength of hospital stay (LOHS) is the main cost-determining factor of hospitalization for stroke patients. However, previous analyses involving LOHS did not consider confounding or indirect factors, or the effects of other factors on LOHS and inpatient costs.ObjectiveTo investigate the direct and indirect effects of LOHS on the hospitalization costs of inpatients with ischemic and hemorrhagic stroke.Design, setting, and participantsThis was a population-based, retrospective, and observational study that analyzed data acquired from the Nationwide Inpatient Sample between 2015 and 2020 relating to ischemic and hemorrhagic stroke in Ningxia, China.Main outcomes and measuresHospitalizations were identified by the International Classification of Diseases 10th Revision (ICD-10). Inpatient costs were described by the median M (P25, P75). We used a quantile regression model to estimate the linear relationships between a group of independent variables X and the quantile of the explained variable hospitalization cost (Y). A structural equation model (SEM) was then used to investigate the direct and indirect effects of LOHS on inpatient costs.ResultsThe study included 129,444 patients with ischemic stroke and 15,525 patients with hemorrhagic stroke. The median LOHS was 10 (8–13) days for ischemic stroke and 15 (10–22) days for hemorrhagic stroke. The median M (P25, P75) of inpatient costs was $1020 (742–1545) for ischemic stroke and 2813 (1576–6191) for hemorrhagic stroke. The total effect of LOHS on inpatient costs was 0.795 in patients with ischemic stroke. The effect of yearof discharge (X4) and CCI (X8) on inpatient costs was dominated by an indirect effect through the LOHS. The indirect effect was −0.071 (84.52% of the total effect value) and 0.034 (69.39% of the total effect value), respectively. The total effect of LOHS on inpatient costs in patients with hemorrhagic stroke was 0.754. The influence of CCI on inpatient costs was dominated by an indirect effect through LOHS; the indirect effect value was −0.028 (77.78% of the total effect value). The payment type, surgery, method of discharge, and hospital level also exerted an impact on inpatient costs by direct and indirect effects through the LOHS.Conclusions and relevanceLength of hospital stay (LOHS) was identified as the main factor influencing hospitalization costs. However, other social factors were shown to indirectly influence hospitalization costs through the LOHS. Taking effective measures to further reduce hospitalization costs remains an effective way to control hospitalization costs for stroke patients.

Proinflammatory laboratory predictors of pneumonia in ischemic stroke patients: prospective study

Bacterial pneumonia is a frequent complication of ischemic stroke at the hospital stage. The search for prognostic laboratory markers of pneumonia remains an urgent task, as it will allow to individualize the approach to the treatment and rehabilitation of such patients. To investigate the prognostic significance of proteins of the acute phase of inflammation, as well as to evaluate them as early predictors of the development of pneumonia in patients with ischemic stroke. The study included 302 patients in the acute period of ischemic stroke. C-reactive protein (CRP), tumor necrosis factor , interleukin-6 (IL-6), neutrophil elastase, neopterin, serum amyloid A (SAA), secreted phospholipase type 2 (sPLA2) were determined in all patients on the first day by enzyme immunoassay. Statistical data processing was carried out using SPSS and Microsoft Excel software (USA). At the hospital stage, pneumonia developed in 82/302 patients (27.2%; 95% confidence interval 22.332.3%). The levels of CRP, IL-6, sPLA2, SAA and neopterin significantly differed in the presence and absence of pneumonia. Step-by-step logistic regression analysis revealed the significance of IL-6 and CRP concentrations in the prognosis of pneumonia. The threshold value of IL-6 concentration was 3.45 pg/ml (sensitivity 82.4%, specificity 66.7%). The prognostic value of a positive result (PPR) in the prognosis of pneumonia was 40%, a negative result (PNR) 92%. The threshold value of CRP was 1640 mg/l with a sensitivity of 65.8% and a specificity of 74.8%. The PPR of the threshold value of the concentration of CRP was 45%, PNR 80%. The measurement of the concentration of IL-6 and CRP on the first day of ischemic stroke makes it possible to identify patients with the greatest risk of pneumonia at the hospital stage. The results of the work indicate the necessity to include CRP and IL-6 in the list of mandatory laboratory tests that should be carried out for each patient with ischemic stroke on the first day from the onset of the disease.

Diagnostic Performance of Circulating miRNAs and Extracellular Vesicles in Acute Ischemic Stroke.

Background: Increased inflammation activates blood coagulation system, higher platelet activation plays a key role in the pathophysiology of ischemic stroke (IS). During platelet activation and aggregation process, platelets may cause increased release of several proinflammatory, and prothrombotic mediators, including microRNAs (miRNAs) and extracellular vesicles (EVs). In the current study we aimed to assess circulating miRNAs profile related to platelet function and inflammation and circulating EVs from platelets, leukocytes, and endothelial cells to analyse their diagnostic and predictive utility in patients with acute IS. Methods: The study population consisted of 28 patients with the diagnosis of the acute IS. The control group consisted of 35 age- and gender-matched patients on acetylsalicylic acid (ASA) therapy without history of stroke and/or TIA with established stable coronary artery disease (CAD) and concomitant cardiovascular risk factors. Venous blood samples were collected from the control group and patients with IS on ASA therapy (a) 24 h after onset of acute IS, (b) 7-days following index hospitalization. Flow cytometry was used to determine the concentration of circulating EVs subtypes (from platelets, leukocytes, and endothelial cells) in platelet-depleted plasma and qRT-PCR was used to determine several circulating plasma miRNAs (miR-19a-3p, miR-186-5p and let-7f). Results: Patients with high platelet reactivity (HPR, based on arachidonic acid-induced platelet aggregometry) had significantly elevated platelet-EVs (CD62+) and leukocyte-EVs (CD45+) concentration compared to patients with normal platelet reactivity at the day of 1 acute-stroke (p = 0.012, p = 0.002, respectively). Diagnostic values of baseline miRNAs and EVs were evaluated with receiver operating characteristic (ROC) curve analysis. The area under the ROC curve for miR-19a-3p was 0.755 (95% CI, 0.63–0.88) p = 0.004, for let-7f, it was 0.874 (95% CI, 0.76–0.99) p = 0.0001; platelet-EVs was 0.776 (95% CI, 0.65–0.90) p = 0.001, whereas for leukocyte-EVs, it was 0.715 (95% CI, 0.57–0.87) p = 0.008. ROC curve showed that pooling the miR-19a-3p expressions, platelet-EVs, and leukocyte-EVs concentration yielded a higher AUC than the value of each individual biomarker as AUC was 0.893 (95% CI, 0.79–0.99). Patients with moderate stroke had significantly elevated miR-19a-3p expression levels compared to patients with minor stroke at the first day of IS. (AUC: 0.867, (95% CI, 0.74–0.10) p = 0.001). Conclusion: Combining different biomarkers of processes underlying IS pathophysiology might be beneficial for early diagnosis of ischemic events. Thus, we believe that in the future circulating biomarkers might be used in the prehospital phase of IS. In particular, circulating plasma EVs and non-coding RNAs including miRNAs are interesting candidates as bearers of circulating biomarkers due to their high stability in the blood and making them highly relevant biomarkers for IS diagnostics.

Personalised Approach to Diagnosing and Managing Ischemic Stroke with a Plasma-Soluble Urokinase-Type Plasminogen Activator Receptor.

Background: The increasing incidence of ischemic stroke has led to the search for a novel biomarker to predict the course of disease and the risk of mortality. Recently, the role of the soluble urokinase plasminogen activator receptor (suPAR) as a biomarker and indicator of immune system activation has been widely examined. Therefore, the aim of the current study was to assess the dynamics of changes in serum levels of suPAR in ischemic stroke and to evaluate the prognostic value of suPAR in determining mortality risk. Methods: Eighty patients from the Department of Neurology, diagnosed with ischemic stroke, were enrolled in the study. Residual blood was obtained from all the patients on the first, third and seventh days after their ischemic stroke and the concentrations of suPAR and C-reactive protein (CRP), as well as the number of leukocytes and National Institute of Health’s Stroke Scale (NIHSS) scores, were evaluated. Results: On the first day of ischemic stroke, the average suPAR concentration was 6.55 ng/mL; on the third day, it was 8.29 ng/mL; on the seventh day, it was 9.16 ng/mL. The average CRP concentration on the first day of ischemic stroke was 4.96 mg/L; on the third day, it was 11.76 mg/L; on the seventh day, it was 17.17 mg/L. The number of leukocytes on the first day of ischemic stroke was 7.32 × 103/mm3; on the third day, it was 9.27 × 103/mm3; on the seventh day, it was 10.41 × 103/mm3. Neurological condition, which was assessed via the NIHSS, on the first day of ischemic stroke, was scored at 10.71 points; on the third day, it was scored at 12.34 points; on the seventh day, it was scored at 13.75 points. An increase in the values of all the evaluated parameters on the first, third and seventh days of hospitalisation was observed. The patients with hypertension, ischemic heart disease and type 2 diabetes showed higher suPAR and CRP concentrations at the baseline as well as on subsequent days of hospitalisation. The greatest sensitivity and specificity were characterised by suPAR-3, where a value above 10.5 ng/mL resulted in a significant increase in mortality risk. Moreover, an NIHSS-1 score above 12 points and a CRP-3 concentration above 15.6 mg/L significantly increased the risk of death in the course of the disease. Conclusions: The plasma suPAR concentration after ischemic stroke is strongly related to the patient’s clinical status, with a higher concentration on the first and third days of stroke resulting in a poorer prognosis at a later stage of treatment. Therefore, assessing the concentration of this parameter has important prognostic value.

Нейротрофічний фактор мозку як маркер відновлення моторних та когнітивних функцій у гострому періоді кардіоемболічного та атеротромботичного ішемічного інсульту

церебральний ішемічний інсульт - одне з найбільш поширених захворювань, що спричиняють психоемоційні, когнітивні та рухові розлади. Сучасні дослідження спрямовані на пошук біологічних маркерів ураження головного мозку при діагностиці інсультів, зокрема, фізичних, візуалізаційних, електрофізіологічних, гістологічних, генетичних та нейрональних, визначення яких може прискорити диференційну діагностику. Мета дослідження – оцінити рівень нейротрофічного фактору мозку в крові, стан моторних і когнітивних функцій в гострому періоді ішемічного інсульту на 1 та 14 добу, а також можливість використання рівня нейротрофічного фактору мозку крові в якості маркера відновлення рухової та інтелектуально-мнестичної сфери при атеротромботичному та кардіоемболічному підтипах ішемічного інсульту. У дослідження було включено 34 особи з діагнозом гострий ішемічний інсульт. Залежно від результатів клінічного обстеження пацієнтів було розподілено на 2 групи: група 1 – пацієнти, в яких ішемічний інсульт виник внаслідок атеросклеротичного ураження судин каротидної системи з розвитком оклюзії за механізмом атеротромбозу (17 осіб), група 2 – пацієнти, у яких ішемічний інсульт виник внаслідок ураження судин каротидної системи з розвитком оклюзії за кардіоемболічним механізмом (17 осіб). Для порівняння клініко-лабораторних показників додатково було виділено контрольну групу (пацієнти неврологічного відділення, які не мали ураження центральної нервової системи - 11 осіб). Обстеження пацієнтів проведено на 1 та 14 добу захворювання. Моторні функції оцінювали за ступенем повсякденної активності життя, що визначали за індексом Бартел, стан когнітивних функцій - за шкалою Mini-Mental State Examination. Індекс Бартел на 1 добу гострого періоду ішемічного інсульту перебував в межах легкої залежності для кардіоемболічного підтипу та помірної - для атеротромботичного. Протягом 14 днів у досліджуваних пацієнтів обох груп відбувалося зростання індексу до рівня повної незалежності у групі 1 та легкого ступеню залежності у групі 2. У обстежених пацієнтів із ішемічним інсультом було визначено середні значення за шкалою Mini-Mental State Examination на рівні помірного когнітивного дефіциту на 1 добу при обох підтипах ішемічного інсульту. Відновлення когнітивних функцій протягом 14 днів після ішемічного інсульту відбувалося тільки у другій групі до легких когнітивних розладів. Концентрація нейротрофічного фактору мозку на 1 добу ішемічного інсульту різко знижувалася порівняно з контрольною групою. Отримані результати дозволяють розглядати визначення мозкового нейротрофічного фактору об’єктивним біомаркером як тяжкості перебігу кардіоемболічного та атеротромботичного ішемічного інсульту, так і прогнозу відновлення моторних і когнітивних функцій.

PRODUCTION OF INTERLEUKINS 1Β, 2, 4, 10 AND C-REACTIVE PROTEIN IN ISCHEMIC STROKE

The aim: The aim of this study was to determine the content of interleukins (IL) 1β, 2, 4, and 10, as well as the generally accepted marker of inflammation - C-reactive protein (CRP) - in the peripheral blood on the first and tenth days of ischemic stroke (IS). Materials and methods: The study involved 25 patients with IS (including 8 people with mild case of neurological disorders, 9 – moderate case and 8 – severe case) and 14 people of the control group. The levels of IL-1β, IL-2, IL-4 and IL-10 in the blood were determined by the immunoenzyme method. Results: It was found that on the first day in patients with IS an increase in the concentration of CRP and all the studied cytokines, especially pro-inflammatory cytokines IL-1β and IL-2, is marked. On the tenth day, the content of pro-inflammatory cytokines and CRP significantly decreases compared to the first day, but remains higher than in the control, but the concentration of anti-inflammatory cytokines (IL-4 and IL-10) continues to increase. Conclusions: The results obtained on the first day of IS indicate the development of neuroinflammation. On the tenth day the severity of the inflammatory process is significantly reduced, but it still occurs. It was also shown that the outcome of IS depends on the concentration of cytokines in the blood: the higher the level of pro-inflammatory interleukins on the first day, the lower the content of anti-inflammatory interleukins and the higher the amount of pro-inflammatory interleukins on the tenth day, the more pronounced the neurological deficit.

Sex differences in the risk of recurrent ischemic stroke after ischemic stroke and transient ischemic attack.

Sex differences in stroke outcomes have been noted, but whether this extends to stroke recurrence is unclear. We examined sex differences in recurrent stroke using data from the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial. We assessed the risk of recurrent stroke in women compared to men using data from the POINT trial. Adults >18 years old were randomized within 12 hours of onset of minor ischemic stroke or transient ischemic attack (TIA), and followed for up to 90 days for ischemic stroke, our primary outcome. We used Cox proportional hazards model adjusted for demographics and stroke risk factors to evaluate the association between sex and stroke recurrence. We used interaction term testing and prespecified subgroup analyses to determine if the association between sex and recurrent stroke differed by age (<60 versus >60 years old), locale (US versus non-US), and index event type (stroke versus TIA). Last, we evaluated whether sex modified the effect of common stroke risk factors on stroke recurrence. Of 4,881 POINT trial participants with minor stroke or high-risk TIA, 2,195 (45%) were women. During the 90-day follow-up period, 267 ischemic strokes occurred; 121 were in women and 146 in men. The cumulative risk of recurrent ischemic stroke was not significantly different among women (5.76%; 95% CI, 4.84%-6.85%) compared to men (5.67%; 95% CI, 4.83%-6.63%). Women were not at a different risk of recurrent ischemic stroke compared to men (hazard ratio [HR], 1.02; 95% CI, 0.80-1.30) in unadjusted models or after adjusting for covariates. However, there was a significant interaction of age with sex (P=0.04). Among patients <60 years old, there was a non-significantly lower risk of recurrent stroke in women compared to men (HR 0.66; 95% CI 0.42-1.05). Last, sex did not modify the association between common stroke risk factors and recurrent stroke risk. Among patients with minor stroke or TIA, the risk of recurrent ischemic stroke and the impact of common stroke risk factors did not differ between men and women.

DL-3n-Butylphthalide Improves Blood-Brain Barrier Integrity in Rat After Middle Cerebral Artery Occlusion.

Objective: DL-3n-butylphthalide (NBP) has beneficial effects in different stages of ischemic stroke. Our previous studies have demonstrated that NBP promoted angiogenesis in the perifocal region of the ischemic brain. However, the molecular mechanism of NBP for blood–brain barrier protection in acute ischemic stroke was unclear. Here, we explored the neuroprotective effects of NBP on blood–brain barrier integrity in the acute phase of ischemic stroke in a rat model.Methods: Adult male Sprague–Dawley rats (n = 82) underwent 2 h of transient middle cerebral artery occlusion and received 90 mg/kg of NBP for 3 days. Brain edema, infarct volume, surface blood flow, and neurological severity score were evaluated. Blood–brain barrier integrity was evaluated by Evans blue leakage and changes in tight junction proteins. We further examined AQP4 and eNOS expression, MMP-9 enzyme activity, and possible signaling pathways for the role of NBP after ischemic stroke.Results: NBP treatment significantly increased eNOS expression and surface blood flow in the brain, reduced brain edema and infarct volume, and improved neurological severity score compared to the control group (p < 0.05). Furthermore, NBP attenuated Evans blue and IgG leakage and increased tight junction protein expression compared to the control after 1 and 3 days of ischemic stroke (p < 0.05). Finally, NBP decreased AQP4 expression, MMP-9 enzyme activity, and increased MAPK expression during acute ischemic stroke.Conclusion: NBP protected blood–brain barrier integrity and attenuated brain injury in the acute phase of ischemic stroke by decreasing AQP4 expression and MMP-9 enzyme activity. The MAPK signaling pathway may be associated in this process.

MEMBRANE-RECEPTOR COMPLEX DYSFUNCTION AS A NEW TARGET FOR THE NEUROTROPHIC THERAPY OF ISCHEMIC STROKE

The aim of the study was the β-adrenergic activity of peripheral blood erythrocyte membranes in the acute period of ischemic stroke (IS). Peripheral blood erythrocytes are the most informative biological tissue for studying many pathogenetic mechanisms, and the work of their membrane-receptor complex (MRC) can very well reflect the functional state of the whole organism, one of the most important criteria for assessing is the adrenergic activity of cytoplasmic membranes in the pathogenesis of IS. This study solves the problem of the finding of the features of changes in the adrenoceptors system in the acute period of IS in the dynamics of the treatment of humans cryopreserved cord blood serum (CCBS). The main scientific results: the obtained results indicate a reduced ability of adrenoceptors (ARs) on erythrocyte membranes to bind blockers due to the desensitisation effect, which is observed from the 1st day of the disease. In the onset of IS, there is a significant increase in the values of β-adrenergic activity of membranes (β-ARM) of erythrocytes in 2.4 times compared with the control. Maximum levels of the indicator (42.43±3.64 CU) are observed in patients with initially severe disease, which indicates significant stress of the sympathoadrenal system (SAS) in these patients. On the 10th day of the disease, there was a decrease in β-ARM relative to the values obtained during hospitalisation. Still, comparing the value of the indicator on the 10th day of IS in both groups, there was an apparent, more significant decrease in β-ARM in the 2nd group of patients, which additionally received CCBS. The use of CCBS contributes to a more pronounced degree of recovery in neurological functions (6.9%) and faster stabilisation of the structure of MRCs in erythrocytes in the form of reducing the values of β-ARM to 16.61±2.86 CU (p&lt;0.05). The area of practical use of the research results: the results of the study can be used to diagnose and treat of the IS. An innovative technological product: A comprehensive approach to assess the β-ARM of peripheral blood erythrocytes in patients with IS by determining the degree of changes in osmotic resistance of erythrocytes (ORE) under the action of adrenergic drugs (AD) is informative and can be used to diagnose of IS. The use of neurotrophic factors is a potentially new method of treating this pathology. Scope of application of the innovative technological product: in the clinical practice of neurological departments for the treatment of patients with strokes

Abstract TMP18: Early versus Late Start of Direct Oral Anticoagulants After an Ischemic Stroke Related to Atrial Fibrillation - An Individual Patient Data Analysis

Background: The optimal timepoint of starting DOAC after an acute ischemic stroke (IS) related to atrial fibrillation (AF) remains unclear. We aimed to compare an early (≤ 5 days of IS) versus late (&gt;5 days of IS) DOAC-start. Methods: Individual patient data analysis of 7 European and Japanese prospective observational cohort studies. We included patients with IS or TIA related to non-valvular AF where a DOAC was started within 30 days. We excluded patients with an intracranial bleeding (ICH) after the index event but prior to DOAC-start. We compared the 30-day rates of recurrent IS and ICH between the groups of early versus late DOAC-start with a landmark analysis at day 5. Results: Overall, 2550 patients were included. Median age was 77 years (IQR 70-84). DOAC were started early in 1362 (53%) patients, late in 1188 (47%). In the whole cohort, 37 patients suffered from a recurrent IS (1.5%), 16 patients (43%) of whom before any DOAC was started. 6 patients (0.2%) had an ICH. In the early DOAC-start group, 23 patients (1.7%) suffered from a recurrent IS after DOAC-start and within 30 days; two patients (0.1%) suffered from ICH after DOAC-start. In the late DOAC-start group, 14 patients (1.2%) suffered from a recurrent IS before DOAC was started; 4 patients (0.3%) suffered from ICH after DOAC-start. In the comparison of late versus early DOAC-groups, no difference in the hazard ratios was observed for the endpoint of recurrent IS (HR = 1.15, 95%CI 0.48-2.73, p=0.76) and ICH (HR = 4.71, 95%CI 0.51-43.10, p=0.17). Conclusion: Our results do not corroborate the concern that early anticoagulation - at least when performed with DOACs - increases the risk of hemorrhagic transformation of the brain infarct compared to late anticoagulation. Given the seven times higher risk of recurrent IS - with almost half of recurrent IS occurring before any DOAC-start - an early DOAC-start after AF-related IS may be reasonable, if inclusion in the ongoing trials (the recommended option) is not possible.

Clinical effectiveness of «thresholdless» low-frequency transcranial magnetic stimulation in patients with ischemic stroke

As you know, complete successful recovery in stroke patients occurs only in 8% of cases, 20% need constant care. The use of innovative rehabilitation technologies, namely «thresholdless» low-frequency transcranial magnetic stimulation, will speed up the process of restoring impaired functions, increase independence in everyday life and, accordingly, the quality of life. To evaluate the effectiveness of use of low-frequency «thresholdless» transcranial magnetic stimulation in the treatment of patients in acute period of ischemic stroke. The study included 93 patients aged from 49 to 68 years on second-third days of ischemic stroke. The 1st (main) group (n=48) received low-frequency «thresholdless» transcranial magnetic stimulation from the «Diamag» apparatus (AlMag-03) daily for 20 minutes, course - 8-10 procedures, with the background of drug treatment, and in addition to classes with an exercise therapy instructor and an occupational therapist. In the 2nd (control) group (n=45), standard therapy was carried out in accordance with the Procedure for rendering medical care to patients with stroke, only with the exception of physiotherapy. Assessment methods: clinical and neurological examination, indicators of duplex scanning of brachiocephalic vessels, Rivermead mobility index, modified Rankin scale, FIM scale (Functional Independence Measure), Hospital anxiety and depression scale (HADS). In patients of the 1st (main) group, an increase in the linear velocity of blood flow in the internal carotid artery on the side of lesion was revealed by 18.1% when compared with the 2nd (control) group (p=0.042); mobility increased by 42.1%, functional independence in everyday life - by 38.1%, muscle strength - by 50%, compared with the 2nd (control) group (p=0.0005). According to the HADS scale, in 29 (60.8%) patients of the main group, psychoemotional disorders were not detected, neither a single case of significantly expressed symptoms of depression (p<0.0001). The inclusion of low-frequency transcranial electromagnetic stimulation in complex rehabilitation leads to the regression of movement disorders, reduces the level of anxiety and depression, improves daily activity and, as a consequence, the quality of life.

Mortality prediction of ischemic stroke patients without thrombectomy by blood total antioxidant capacity.

It has been previously established that total antioxidant capacity concentrations of blood on the first day of ischemic stroke could predict mortality. Therefore, our study objective was to determine whether total antioxidant capacity concentrations in the blood during the first week of a cerebral infarction could help predict mortality. We included severe and malignant middle cerebral artery infarction patients (affecting 50% or more of the territory in computed tomography and a score of nine or fewer points in the Glasgow Coma Scale). Serum total antioxidant capacity concentrations were determined on days first, fourth, and eighth of the diagnosis of a malignant middle cerebral artery infarction. Higher serum total antioxidant capacity concentrations at first (P < 0.001), fourth (P < 0.001), and eighth (P = 0.003) day were found in non-surviving patients than in surviving ones. Serum total antioxidant capacity concentrations on first, fourth and eighth day of malignant middle cerebral artery infarction had an area under curve (95% Confidence Intervals) for 30-day mortality prediction of 0.86 (0.75-0.93; P < 0.001), 0.87 (0.74-0.95; P < 0.001) and 0.79 (0.64-0.90; P = 0.004)), respectively. Thus, the potential use of serum total antioxidant capacity concentrations at any time during the first 7 days of a severe malignant middle cerebral artery infarction without thrombectomy to predict mortality was the main novel finding of our study.

The importance of selected markers of inflammation and blood-brain barrier damage for short-term ischemic stroke prognosis.

Acute cerebral ischemia triggers local and systemic immune response. The aims of this project was to assess the blood serum concentration of the markers of inflammation and markers of the blood brain barrier damage on the first day of ischemic stroke, and the mutual correlations between these marker levels. Patients with first-in-life stroke were analysed according to: plasma concentration of the following markers on the first day of stroke: interleukin 2 (IL-2) and interleuki 6 (IL-6), S100B, tumor necrosis factor-α (TNF-α), progranulin (GRN), neuron specific enolase (NSE), urokinase-type plasminogen activator (uPA), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), C-reactive protein (CRP), leucocyte and thrombocyte counts; their neurological status on the first day of stroke (NIHSS) and their functional status at 30 days following stroke (mRS). The study included 138 patients with mean age: 73.11 ± 11.48. Patients with a higher score on the NIHSS showed significantly higher concentrations of TNF-α, white blood cells (WBC), CRP, NSE, IL-6 and S100B. Patients with a higher score on the modified Rankin Score (mRS) showed significantly higher concentrations of WBC, CRP, GRN, IL-6, S100B. Factors with an independent influence on the neurological status on the first day of stroke were: sex, WBC, total blood platelet (PLT) count, CRP, S100B and IL-6 levels. Atrial fibrillation, leukocyte count, CRP, NSA, uPA, IL-6 and S100B showed an independent impact on the functional status on the 30th day of stroke. Patients with symptomatic atherosclerosis, as compared to others, were older (P = 0.003) and had higher levels of CRP, IL-6, and S100B. In each case, the differences were statistically significant. We conclude that the concentration of Il-6 and S100B on the first day of stroke are important for both the neurological status and the functional status in the acute period of the disease. Increased CRP and leukocyte count are associated with a worse prognosis regarding the course of acute stroke. The expression of pro-inflammatory agents and markers of blood-brain barrier damage in the acute phase of stroke seem to be more prominent in patients with symptomatic atherosclerosis than in patients with no clinical features of atherosclerosis. The expression of inflammatory parameters may indicate the importance of the inflammatory process starting during the early days of ischemic stroke, for the post-stroke neurological deficit.

Апоптоз и фенотип тромбоцитов у больных с острым ишемическим инсультом

Aim. To develop of knowledge of platelet apoptosis and phenotype in patients with acute ischemic stroke and to study the prognostic value of some membrane-bound proteins. Method. The study included 18 patients aged 59-78 with acute ischemic stroke. Platelet were isolated by immonomagnetic separation within the first 24 hours and at 7 days of ischemic stroke. The expression of surface antigens was measured using monoclonal antibodies. For detection of phosphatidylserine (PS) externalization platelets were incubated with Annexin V. The mitochondrial membrane potential (MMP) was measured using JC-1 during platelets apoptosis. Immediately after the incubation, platelets were analyzed by flow cytometry. Results. On day 1 of stroke, the expression of CD62p (P-selectin) was higher than in healthy subjects (18.3% vs . 4.1%, respectively, p&lt;0.05). The PS externalization on platelets from patients with stroke was significantly higher than in healthy subjects (20.6% vs. 3.2%, respectively, p&lt;0.01). A decrease in MMP to 70% was observed in platelets from patients with stroke compared to 94% in the control group (p&lt;0.05). Conclusion. Therefore, acute ischemic stroke was associated with the following platelet abnormalities: increased PS expression and declined MMP in parallel with increased P-selectin expression, which reflects platelet activation. Further studies of platelet phenotype and apoptosis biomarkers will provide a deeper insight into the pathogenetic role of platelets in ischemic stroke and contribute to the development of methods for monitoring effects of antiplatelet therapy.

Abstract TMP81: Nationally Representative Estimates of Readmission Rates After Extracranial-Intracranial Bypass Surgery for Moyamoya Disease

Background: International trials have suggested benefit of extracranial- intracranial bypass (ECICB) for Moyamoya disease (MMD). However, nationally representative US data on demographics and adverse outcomes after ECICB in MMD are lacking. We aimed to estimate nationally representative 30, 60 and 90-day readmission rates for ischemic stroke (IS), subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH) after an index admission for MMD with ECICB. Methods: The Nationwide Readmissions Database contains data on &gt;14 million discharges for all payers and the uninsured in 2013. Index admissions for ECICB for MMD, and readmissions for IS, SAH, and ICH, were identified using validated International Classification of Diseases, 9th Revision, Clinical Modification codes. We summarized demographics, comorbidities, and the Charlson Comorbidity Index (CCI) during the index admission, and calculated 30-, 60-, and 90-day readmission rates per 100,000 index admissions. Preventable causes of admission were determined by Prevention Quality Indicators. Results: Among 201 index admissions for ECICB for MMD, mean age (SD) was 41.7 (12.6) years; 75% were female; 24% had diabetes; 53% had hypertension; 40% had hypercholesterolemia; and mean CCI (SD) was 3.2 (1.5). For concurrent or previous cerebrovascular events, 3% had ICH; 16% had IS; and 1% had SAH. ECICB was performed at large hospitals in 83%, urban hospitals in 85%, and teaching hospitals in 97%. 80% were discharged home. 1% died during index hospitalization. 34% had a readmission during follow-up, 3% of which were preventable. Leading reasons for readmission up to 90 days included MMD (62%), postoperative infection (10%), sickle cell crisis (4%), ischemic stroke (4%), epilepsy (2%), subdural hemorrhage (2%) and headache (2%). Readmission rates (per 100,000 index admissions) were 559 at 30 days, 1829 at 60 days, and 2027 at 90 days for IS. There were no readmissions for SAH or ICH. Conclusions: This analysis of nationally representative US data suggests that although readmission after ECICB for MMD is not uncommon, cerebral hemorrhagic events during the 90-day postoperative period are rare. Readmission for ischemic stroke, in comparison, is more prevalent, and only 3% of readmissions were preventable.