Development Of Acute Ischemic Stroke Research Articles

Anterior circulation acute ischemic stroke due to vertebral artery ostial stenosis in a patient with congenital internal carotid artery agenesis: a case report

BackgroundCongenital agenesis of internal carotid artery (ICA) is a rare cerebrovascular variation entity. Most cases of congenital ICA agenesis are asymptomatic and discovered incidentally. Congenital ICA agenesis presenting as ischemic stroke is even rare.Case presentationAn 80-year-old male patient was admitted to our hospital due to sudden dysarthria and left limb weakness for 3.5 h. Based on emergency physical examination and head computed tomography (CT) scan results, acute ischemic stroke (AIS) of right cerebral hemisphere was suspected. Following intravenous thrombolysis with recombinant tissue plasminogen activator, right congenital agenesis of ICA was confirmed by CT and digital subtraction angiography. Additionally, there was a severe right vertebral artery ostial (VAO) stenosis. After ruling out common causes of AIS such as haematological diseases, arterial dissection, organic heart disease, immunological abnormality and underlying possible malignancies, we hypothesize that the severe stenosis of the right VAO may have contributed to the development of AIS in this case.ConclusionsWe present a case of right congenital ICA agenesis in which severe stenosis of the right VAO may have played a role in the development of AIS. This case underscores a rare scenario where a lesion in the posterior circulation leads to an infarction in the anterior circulation in the setting of congenital ICA agenesis.

Role of Circadian Rhythm Changes on Functional Dependence Despite Successful Repercussion in Patients with Endovascular Treatment.

Increasing evidence of circadian biology may influence the physiopathologic mechanism, progression, and recovery of stroke. However, few data have shown about circadian rhythm on futile recanalization (FR) in patients treated with endovascular treatment (EVT). From 2017 to 2021, an observational cohort of acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) underwent EVT was conducted. FR was defined as the failure to achieve functional independence in patients at 90 days after EVT, although the occluded vessels reached a recanalization. The effect of circadian rhythm on FR was investigated using the logistic regression model. Of 783 patients, there were 149 patients who had stroke onset between 23:00-6:59, 318 patients between 7:00-14:59, and 316 patients between 15:00-22:59. Patients suffered a stroke during 15:00-22:59 had shorter OTP (p =0.001) time, shorter OTR (p<0.001) time, higher rate of intravenous thrombolysis (p =0.001) than groups of other time intervals. The rate of FR post-EVT in patients who had a stroke between 15:00-22:59 was significantly higher than in those with stroke onset between 23:00-6:59 (p =0.017). After adjusting for confounding factors, the time of stroke occurring during 15:00-22:59 (adjusted OR [aOR], 1.652; 95%CI, 1.024-2.666, p =0.04) was an independent predictor of FR. Circadian rhythm can directly or indirectly affect the occurrence, development, and prognosis of AIS. More studies may be needed in the future to validate the results of our study and to explore the potential mechanisms behind the effects of circadian rhythms on FR.

Investigating the potential of catheter-assisted pulsed focused ultrasound ablation for atherosclerotic plaques.

Atherosclerosis is a condition in which an adhesive substance called plaque accumulates over time inside the arteries. Plaque buildup results in the constriction of arteries, causing a shortage of blood supply to tissues and organs. Removing atherosclerotic plaques controls the development of acute ischemic stroke and heart diseases. It remains imperative for positive patient outcomes. This study sought to develop a minimally invasive technique for removing arterial plaques by applying focused ultrasound (FUS) energy on the metal surface of a nitinol catheter wire to induce inertial cavitation. The induced cavitation can deplete plaque mechanically inside the arteries, leading towards improved recanalization of blood vessels. The enhanced cavitation effect induced by combining FUS with a metal catheter was first verified by exposing agar phantom gels with or without a 0.9-mm diameter nitinol wire to an acoustic field produced by a 0.5-MHz FUS transducer. The phenomenon was further confirmed in pork belly fat samples with or without a 3-mm diameter nitinol catheter wire. Cavitation was monitored by detecting the peaks of emitted ultrasound signals from the samples using a passive cavitation detector (PCD). Cavitation threshold values were determined by observing the jump in the peak amplitude of signals received by the PCD when the applied FUS peak negative pressure (PNP) increased. To simulate arterial plaque removal, FUS with or without a catheter was used to remove tissues from pork belly fat samples and the lipid cores of human atherosclerotic plaque samples using 2500-cycle FUS bursts at 10% duty cycle and a burst repetition rate of 20Hz. Treatment outcomes were quantified by subtracting the weight of samples before treatment from the weight of samples after treatment. All measurements were repeated 5 times (n=5) unless otherwise indicated, and paired t-tests were used to compare the means of two groups. A p-value of <0.05 will be considered significant. Our results showed that with a nitinol wire, the cavitation threshold in agar phantoms was reduced to 2.6MPa from 4.3MPa PNP when there was no nitinol wire in the focal region of FUS. For pork belly fat samples, cavitation threshold values were 1.0 and 2.0MPa PNP, with and without a catheter wire, respectively. Pork belly fat tissues and lipid cores of atherosclerotic plaques were depleted at the interface between a catheter and the samples at 2 and 4MPa FUS PNP, respectively. The results showed that with a catheter wire in the focal region of a 3-min FUS treatment session, 24.7 and 25.6mg of lipid tissues were removed from pork belly fat and human atherosclerotic samples, respectively. In contrast, the FUS-only group showed no reduction in sample weight. The differences between FUS-only and FUS-plus-catheter groups were statistically significant (p<0.001 for the treatment on pork belly samples, and p<0.01 for the treatment on human atherosclerotic samples). This study demonstrated the feasibility of catheter-assisted FUS therapy for removing atherosclerotic plaques.

Brain-Derived Exosomal CircRNAs in Plasma Serve as Diagnostic Biomarkers for Acute Ischemic Stroke.

Acute ischemic stroke (AIS), commonly known as stroke, is a debilitating condition characterized by the interruption of blood flow to the brain, resulting in tissue damage and neurological deficits. Early diagnosis is crucial for effective intervention and management, as timely treatment can significantly improve patient outcomes. Therefore, novel methods for the early diagnosis of AIS are urgently needed. Several studies have shown that bioactive molecules contained in extracellular vesicles, especially circRNAs, could be ideal markers for the diagnosis of many diseases. However, studies on the effects of exosomes and their circRNAs on the development and prognosis of AIS have not been reported extensively. Therefore, we explored the feasibility of using circRNAs in plasma brain-derived exosomes as biomarkers for AIS. By high-throughput sequencing, we first identified 358 dysregulated circRNAs (including 23 significantly upregulated circRNAs and 335 significantly downregulated circRNAs) in the plasma brain-derived exosomes of the brain infarct patient group compared to those of the noninfarct control group. Five upregulated circRNAs (hsa_circ_0007290, hsa_circ_0049637, hsa_circ_0000607, hsa_circ_0004808, and hsa_circ_0000097) were selected for further validation via Real-Time Quantitative Reverse Transcription PCR (qRT‒PCR) in a larger cohort based on the exclusion criteria of log2FC > 1, p < 0.05 and measurable expression. We found that the expression levels of hsa_circ_0007290, hsa_circ_0049637, hsa_circ_0000607, hsa_circ_0004808 and hsa_circ_0000097 were significantly upregulated in AIS patients and could serve as potential biomarkers for AIS with high specificity and sensitivity. Moreover, the expression levels of hsa_circ_0007290, hsa_circ_0049637, hsa_circ_0000607, hsa_circ_0004808 and hsa_circ_0000097 were also found to be positively correlated with National Institutes of Health Stroke Scale (NISS) and modified Rankin scale (mRS) scores, which indicated that the presence of these circRNAs in plasma brain-derived exosomes could also determine the progression of AIS.

The lncRNA lnc_AABR07044470.1 promotes the mitochondrial-damaged inflammatory response to neuronal injury via miR-214-3p/PERM1 axis in acute ischemic stroke

PurposeWe investigated the role of lnc_AABR07044470.1 on the occurrence and development of acute ischemic stroke (AIS) and neuronal injury by targeting the miR-214-3p/PERM1 axis to find a novel clinical drug target and prediction and treatment of AIS.MethodsThe mouse AIS animal model was used in vivo experiments and hypoxia/reoxygenation cell model in vitro was established. Firstly, infarction volume and pathological changes of mouse hippocampal neurons were detected using HE staining. Secondly, rat primary neuron apoptosis was detected by flow cytometry assay. The numbers of neuron, microglia and astrocytes were detected using immunofluorescence (IF). Furthermore, binding detection was performed by bioinformatics database and double luciferase reporter assay. Lnc_AABR07044470.1 localization was performed using fluorescence in situ hybridization (FISH).Lnc_AABR07044470.1, miR-214-3pand PERM1mRNA expression was performed using RT-qPCR. NLRP3, ASC, Caspase-1 and PERM1 protein expression was performed using Western blotting. IL-1β was detected by ELISA assay.ResultsMouse four-vessel occlusion could easily establish the animal model, and AIS animal model had an obvious time-dependence. HE staining showed that, compared with the sham group, infarction volume and pathological changes of mouse hippocampal neurons were deteriorated in the model group. Furthermore, compared with the sham group, neurons were significantly reduced, while microglia and astrocytes were significantly activated. Moreover, the bioinformatics prediction and detection of double luciferase reporter confirmed the binding site of lnc_AABR07044470.1 to miR-214-3p and miR-214-3p to Perm1. lnc_AABR07044470.1 and PERM1 expression was significantly down-regulated and miR-214-3pexpression was significantly up-regulated in AIS animal model in vivo. At the same time, the expression of inflammasome NLRP3, ASC, Caspase-1 and pro-inflammatory factor IL-1β was significantly up-regulated in vivo and in vitro. The over-expression of lnc_AABR07044470.1 and miR-214-3p inhibitor could inhibit the neuron apoptosis and the expression of inflammasome NLRP3, ASC, Caspase-1 and pro-inflammatory factor IL-1β and up-regulate the expression of PERM1 in vitro. Finally, over-expression of lnc_AABR07044470.1 and miR-214-3p inhibitor transfected cell model was significant in relieving the AIS and neuronal injury.ConclusionLnc_AABR07044470.1 promotes inflammatory response to neuronal injury via miR-214-3p/PERM1 axis in AIS.

The Interplay of Dyslipidemia, Oxidative Stress, and Clinical Outcomes in Acute Ischemic Stroke Patients with and without Coronary Artery Disease.

We assessed lipid and lipoprotein profiles, along with oxidative stress (OS) parameters, in patients within the crucial 24 h period following an acute ischemic stroke (AIS), comparing those with and without coronary artery disease (CAD). We aimed to correlate these measures with clinical condition scales (NIHSS, mRS) post-AIS. This study included 27 AIS patients without CAD (AIS group) and 37 AIS patients with CAD (CAD-AIS group). Using polyacrylamide gel electrophoresis (Lipoprint system), we determined plasma LDL and HDL subfractions. Spectrophotometric methods were used to assess plasma antioxidant capacity, lipoperoxides, homocysteine (HC) levels, paraoxonase1, and catalase activities. We also measured urine isoprostanes and the activities of antioxidant enzymes (SOD, GPx) with commercial kits. CAD-AIS patients had notably higher HC levels, while there were no significant differences in lipoprotein subfractions and OS parameters between both groups. In the AIS group, mRS scores showed negative correlations with catalase, GPx activities, and total cholesterol. In the CAD-AIS group, atherogenic lipoproteins (IDLC, LDL2, LDL3-7) exhibited a significant positive correlation with mRS. This study underscores the role of dyslipidemia and OS in the development of AIS and CAD. It emphasizes the complex connections between specific biomarkers and post-stroke clinical outcomes. Our results suggest a significant impact of CAD treatment on lipid profile but not on homocysteine levels. The traditional narrative associating high cholesterol as the ultimate risk factor for cardiovascular diseases needs to be challenged, at least with respect to neurological outcomes. These insights may guide more targeted therapeutic approaches.

Acute ischemic stroke in Tsutsugamushi: understanding the underlying mechanisms and risk factors

BackgroundTsutsugamushi (scrub typhus) is an acute infectious febrile disease common in the Asia-Pacific region. Common symptoms of tsutsugamushi include lymphadenopathy, fever, and myalgia, and it rarely causes acute ischemic stroke (AIS). However, we hypothesized that tsutsugamushi infection could trigger AIS.MethodWe retrospectively examined patients diagnosed with AIS within 2 weeks of tsutsugamushi diagnosis at three hospitals over a 15-year period. We categorized patients who developed AIS while being treated for tsutsugamushi as the case group and those (of similar age and sex) who did not develop AIS as the control group. The case and control groups consisted of 22 and 66 participants, respectively. When a scattered pattern was observed or lesions were found in two or more vascular territories on diffusion-weighted imaging, the pattern was defined as embolic. Other patterns were defined as nonembolic.ResultsAmong the 19 patients, excluding three with transient ischemic stroke, 15 (78.9%) showed an embolic pattern. Although fever was common in the control group, it was less common in the case group. A higher D-dimer level at the time of hospitalization was associated with the development of AIS in patients with tsutsugamushi.ConclusionsAIS in patients with tsutsugamushi showed an embolic rather than a non-embolic pattern on brain magnetic resonance imaging. It was more likely to occur in patients with risk factors for stroke. Tsutsugamushi patients with AIS were likely to have no fever or high D-dimer levels. We hypothesized that D-dimers play an important role in the pathophysiology, where tsutsugamushi infection increases the likelihood of AIS.

Chuanzhitongluo Inhibits Neuronal Apoptosis in Mice with Acute Ischemic Stroke by Regulating the PI3K/AKT Signaling Pathway

Background and purpose: Apoptosis is involved in the occurrence and development of acute ischemic stroke (AIS). This study aimed to assess whether Chuanzhitongluo (CZTL), a multi-target and multi-pathway compound preparation, plays a neuroprotective role in AIS by modulating neuronal apoptosis via the PI3K/AKT signaling pathway. Methods: A mouse model of AIS was established by photochemical processes. Cerebral infarction volume was measured by 2% staining with 2, 3, and 5-triphenyl tetrazole chloride (TTC). Neuron apoptosis was assessed by TUNEL staining. Apoptosis RNA arrays were used to detect changes in apoptosis-related gene expression profiles. Western blotting was used to detect proteins involved in the PI3K/AKT signaling pathway. Results: The study demonstrated that CZTL could potentially mitigate neuronal apoptosis in AIS mice. This appears to be achieved via the up-regulation of certain genes such as BCL-2, Birc6, and others, coupled with the down-regulation of genes like BAX, Bid, and Casp3. Further validation revealed that CZTL could enhance the expression of BCL-2 and reduce the expression of Cleaved Caspase-3 and BAX at both the gene and protein levels. The study also found that CZTL can enhance the phosphorylation level of the PI3K/AKT signaling pathway. In contrast to these findings, the PI3K inhibitor LY294002 notably amplified neuronal apoptosis in AIS mice. Conclusions: These findings imply that CZTL's ability to inhibit neuronal apoptosis may be linked to the activation of AIS's PI3K/AKT signaling pathway.

Abstract 055: Reperfusion Therapy for Acute Ischemic Stroke in Cardiomyopathy Patients with Heart Failure: A NIS‐based Analysis

Introduction Cardiomyopathy (CM) is a diverse pathology defined by both structural and functional changes in the heart. Many studies have aimed to determine if heart failure (HF) is an independent risk factor in the development of AIS, but there is a paucity of literature describing the interventions and functional outcomes in this group of patients. We aimed to investigate the safety of intravenous tissue plasminogen activator (IV tPA) and mechanical thrombectomy (MT) for acute ischemic stroke (AIS), and compare the functional outcome in cardiomyopathy patients with and without HF. We hypothesized that CM and HF patients would have higher rates of mortality and complications but would still benefit from reperfusion therapy with improved functional outcomes. Methods This is a multi‐center, retrospective study. The National Inpatient Sample (NIS) database from 2016‐2019 for patients with a principal diagnosis of AIS using the ICD‐10 code I63 was queried. AIS patients with CM and HF were compared to those without. Outcome measures studied included prolonged length of stay (LOS), discharge disposition, and inpatient mortality. Results We identified 2,939,160 patients with AIS between 2016 and 2019. Of those patients, 2.8% (80,915) had concomitant diagnoses of both CM and HF. Compared to matched cohorts, CM‐HF patients were more likely to be younger (age &lt;80: 22.4% v. 27.3%, p &lt; 0.001), male (61.8% v. 49.8%, p &lt; 0.001), and African American (29.5% v. 16.4%, p &lt; 0.001). Additionally, CM‐HF patients had higher rates of medical comorbidities such as atrial fibrillation (43.6% v. 24.2%, p &lt; 0.001), diabetes mellitus (39.7% v. 37.6%, p &lt; 0.001), obesity (9.2% v. 8.3%, p &lt; 0.001), and obstructive sleep apnea (10.9% v. 7.3%, p &lt; 0.001). CM‐HF patients were more likely to have an Elixhauser Comorbidity Index &gt; 2 (99.4% v. 90.9%, p &lt; 0.001). Lastly, this cohort was more likely to use anticoagulant medication (18.1% v. 9.5%, p &lt; 0.001). CM‐HF patients were more likely to have a severe stroke (25.9% v. 19.6%, p &lt; 0.001). Additionally, CM‐HF patients were more likely to receive both EVT (8.8% v. 5.6%, p &lt; 0.001) and EVT and tPA (0.9% v. 0.6%, p &lt; 0.001). An analysis of the rates of post‐intervention intracerebral hemorrhage showed that there was no significant difference observed between groups. This finding was regardless of the type of intervention received, including tPA (15.9% v. 13.6%, p = 0.192), EVT (15.6% v. 17.4%, p = 0.171), or both tPA and EVT (25.9% v. 22.3%, p= 0.321). CM‐HF patients had higher rates of in‐patient complications such as PEG placement, tracheostomy, sepsis, DVT or PE, pneumonia, UTI, AKI, myocardial infarction, and intracerebral hemorrhage. CM‐HF patients were more likely to have a prolonged LOS (47.8% v. 31.4%, p &lt; 0.001) and higher rates of inpatient death (6.6% v. 5.4%, p &lt; 0.001). Despite these outcomes, CM‐HF patients were less likely to have a non‐favorable discharge to both a skilled nursing facility (43.8% v. 44.9%, p &lt; 0.001) and short‐term hospitalization (2.8% v. 4.6%, p &lt; 0.001). Rates of favorable discharge were higher for CM‐HF patients (45.7% v. 43.9%, p &lt; 0.001). Conclusion Patients with AIS and concomitant HF and CM are more likely to have favorable functional outcomes despite having higher rates of inpatient death and in‐hospital complications. Reperfusion therapies can be used safely in CM and HF patients.

Abstract 071: Oral Contraceptive Use and Development of Acute Ischemic Stroke: A Population‐Based Retrospective Cohort Study

Introduction Existing evidence remains conflicting regarding the association between oral hormonal contraceptive (OCP) use and the risk of acute ischemic stroke (AIS). Large‐scale analyses and observational data evaluating this clinical question in recent years are scarce, despite widespread use of hormonal contraception in adult females of child‐bearing age. Modern OCP formulations contain lower doses of estrogen, the putative causative agent for AIS in this population, and underscores the need to re‐evaluate the risk initially demonstrated in older formulations containing higher levels of estrogen. Methods Hospitalizations for female patients aged 15‐50 were identified in the National Inpatient Sample (NIS) registry from 2015‐2020, excluding admissions associated with pregnancy or the postpartum period. The study exposure was use of OCPs and the primary endpoint was AIS, identified by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD‐10‐CM) coding. Propensity score (PS) adjustment by inverse probability weighting (IPW) was used to mimic the effects of randomization by balancing baseline clinical characteristics associated with stroke between OCP and non‐OCP users to reduce measured confounding. In addition to age and race/ethnicity, a battery of more than forty confounding covariates representing established risk factors for AIS in the general and young population were identified (cardiovascular disease, lifestyle risk factors, congenital abnormalities, vasculopathies, hypercoagulable states, migraine with aura, among others) and balanced between OCP and non‐OCP users. Sensitivity testing was performed by evaluating stroke incidence in a sub‐group of patients without any risk factors present and by assessing a negative control (head trauma), with which an association of OCP use would not be expected. The effect size of the association between OCPs and AIS was presented as an adjusted odds ratio (aOR) with 95% confidence interval (CI), with statistical significance evaluated at p &lt; 0.001. Results PS adjustment by IPW to balance all available AIS risk factors between OCP users and non‐users yielded 23,253,209 hospitalizations, 11,654,398 (50.1%) of which were associated with OCP use. The incidence of AIS was significantly greater in OCP users compared to non‐OCP users (2.8% vs. 0.4%; aOR 7.50, 95% CI 7.43 to 7.58; p &lt; 0.001). Sub‐group analysis of hospitalizations without any stroke risk factors also demonstrated a significant association of OCP use with the development of AIS (1.3% vs. 0.1%; aOR 14.84, 95% CI 13.16 to 16.72; p &lt; 0.001) following adjustment for age and race/ethnicity. In negative control analysis, OCP use was not associated with admissions associated with head trauma (1.4% vs. 1.4%; OR 1.03, 95% CI 0.95 to 1.10; p = 0.485). Conclusion Retrospective observational data from the United States in recent years suggests an association between OCP use and AIS, independent of well‐established risk factors for stroke and despite widespread adoption of lower estrogen formulations.

Hsa-miR-877-5p Expression in Acute Ischemic Stroke Based on Bioinformatics Analysis and Clinical Validation.

Inflammation and immunity play important roles in the pathogenesis of ischemic stroke. This study aimed to explore key regulatory genes in acute ischemic stroke (AIS) and their underlying mechanisms to provide new research targets for the diagnosis and treatment of ischemic stroke. We searched for differentially expressed mRNAs and miRNAs in patients with AIS and healthy populations in GEO databases, constructed a miRNA-mRNA network, and screened key miRNAs using least absolute shrinkage and selection operator regression and the support vector machine-recursive feature elimination model. Correlations between key miRNAs and infiltrating immune cells and inflammatory factors were analyzed using CIBERSORT and immunoassays and verified using clinical experiments. Bioinformatics analysis identified hsa-miR-877-5p as a key regulatory miRNA in AIS that can modulate immune and inflammatory responses. In clinical studies, it was verified by quantitative PCR analysis that the expression of hsa-miR-877-5p in the blood of AIS patients was higher than that of the healthy group. Then, enzyme-linked immunosorbent assay revealed that the expression of IL-23 and TNF-α related to inflammation in AIS patients was higher than that of the healthy. Quantitative PCR further found that the relative mRNA expression of IL-23, CXCR3, and TNF-α in AIS group was higher than that of the healthy group. This study may provide a basis for a more comprehensive understanding of the potential mechanism of the occurrence and development of AIS, and hsa-miR-877-5p and its downstream effectors IL-23, CXCR3, and TNF-α may be potential intervention targets in AIS.

Protein Z and Protein Z-dependent protease inhibitor in patients with acute ischemic stroke: A prospective mechanistic study

ObjectivesProtein Z (PZ) /Protein Z-dependent protease inhibitor (ZPI) (PZ/ZPI) system is a new anticoagulant system discovered in recent years, which plays an important role in many diseases. We aimed to compare the plasma PZ/ZPI levels of acute ischemic stroke (AIS) patients and non-stroke control participants and the role of PZ/ZPI in the development of stroke was preliminarily analyzed. Materials and methodsEnzyme linked immunosorbent assay (ELISA) was used to detect and compare plasma PZ levels of 86 patients with acute AIS and 85 non-stroke control patients. Multivariable Logistic regression was used to analyze whether PZ was an independent risk factor for AIS. ResultsIn the present study, plasma PZ is closely related to inflammatory response, coagulation process and platelet activation, and may participate in the development of AIS by inducing inflammatory responses and interfering with the coagulation process. ConclusionsOur results suggested that plasma PZ level is one of the independent risk factors of AIS, and plasma ZPI was closely related to coagulation and platelet parameter and may play a role in the coagulation process during AIS.

Endotheliitis and cytokine storm as a mechanism of clot formation in COVID-19 ischemic stroke patients: A histopathologic study of retrieved clots.

Studies during the COVID-19 pandemic have demonstrated an association between COVID-19 virus infection and the development of acute ischemic stroke, particularly large vessel occlusion (LVO). Studying the characteristics and immunohistochemistry of retrieved stroke emboli during mechanical thrombectomy for LVO may offer insights into the pathogenesis of LVO in COVID-19 patients. We examined retrieved COVID-19 emboli from the STRIP, EXCELLENT, and RESTORE registries and compared their characteristics to a control group. We identified COVID-positive LVO patients from the STRIP, RESTORE, and EXCELLENT studies who underwent mechanical thrombectomy. These patients were matched to a control group controlling for stroke etiology based on Trial of Org 10172 in Acute Stroke Treatment criteria. All clots were stained with Martius Scarlet Blue (MSB) along with immunohistochemistry for interleukin-6 (IL-6), C-reactive protein (CRP), von Willebrand factor (vWF), CD66b, fibrinogen, and citrullinated Histone H3. Clot composition was compared between groups. Nineteen COVID-19-positive patients and 38 controls were included. COVID-19-positive patients had a significantly higher percentage of CRP and vWF. There was no difference in IL-6, fibrin, CD66b, or citrullinated Histone H3 between groups. Based on MSB staining, there was no statistically significant difference regarding the percentage of red blood cells, white blood cells, fibrin, and platelets. Our study found higher concentrations of CRP and vWF in retrieved clots of COVID-19-positive stroke patients compared to COVID-19-negative controls. These findings support the potential role of systemic inflammation as indicated by elevated CRP and endothelial injury as indicated by elevated vWF as precipitating factors in thrombus development in these patients.

Revisiting the Smoking Paradox in Acute Ischemic Stroke Patients: Findings From the Chinese Stroke Center Alliance Study.

Background Smoking is a well-established risk factor for the development of acute ischemic stroke (AIS). However, the "smoker's paradox" suggests that it is associated with favorable clinical outcomes following stroke. We aimed to reevaluate the association between smoking and in-hospital outcomes in patients with AIS in contemporary practice. Methods and Results A total of 649 610 inpatients with AIS from 1476 participating hospitals in the Chinese Stroke Center Alliance were included. In-hospital outcomes measurement included all-cause mortality, discharge against medical advice, and complications. Multivariable logistic regression models adjusting for baseline characteristics, clinical profiles at presentation, and in-hospital management were used to evaluate the association between smoking and in-hospital outcomes. A propensity score-matched analysis was also conducted. Of these patients with AIS, 36.8% (n=238 912) were smokers. Smokers were younger, had fewer comorbidities, and had slightly lower rates of adverse in-hospital outcomes than nonsmokers (all-cause death or discharge against medical advice: 6.0% versus 6.1%; in-hospital complications: 14.5% versus 15.1%). Multivariable analysis revealed that smoking was associated with higher risk of adverse in-hospital outcomes (all-cause death or discharge against medical advice: odds ratio [OR], 1.05 [95% CI, 1.02-1.08]; P<0.001; complications: OR, 1.06 [95% CI, 1.04-1.08]; P<0.001). The excess risk of adverse in-hospital outcomes remained in smoking patients with AIS after propensity score-matching analysis (all-cause death or discharge against medical advice: OR, 1.04 [95% CI, 1.00-1.08]; P=0.034; complications: OR, 1.05 [95% CI, 1.03-1.08]; P<0.001). Conclusions Smoking was associated with increased risk of adverse in-hospital outcomes among patients with AIS in contemporary practice, reinforcing the importance of smoking cessation in patients with AIS.

Higher serum lipocalin 2 is associated with post-stroke depression at discharge

Background and aimsPost-stroke depression (PSD), as one of the common complications after stroke, seriously affects the physical and mental health and functional prognosis of patients. Previous studies have shown that the increase of inflammatory mediators is associated with the occurrence of PSD. Lipocalin 2 (LCN2), as an acute phase protein, is involved in the development of acute ischemic stroke (AIS), and its expression is up-regulated in patients with depression, suggesting that there is a potential correlation between serum LCN2 and depression. The aim of this study was to explore the relationship between serum LCN2 at admission and PSD at discharge.MethodsA total of 358 AIS patients were retrospectively included. All patients had fasting venous blood taken within 24 h of admission to detect serum LCN2. The patients were evaluated by 17-item Hamilton Depression Scale (HAMD) before discharge. Patients with HAMD score > 7 were diagnosed with PSD. The correlation between serum LCN2 and PSD was tested using binary logistic regression analysis.ResultsIn our study, 92 (25.7%) patients were diagnosed with PSD at discharge. According to the serum LCN2 value, the patients were divided into three layers (Tertile1 ≤ 105.24ng/ml; Tertile2: 105.24-140.12ng/ml; Tertile3 ≥ 140.12ng/ml), with T1 layer (the lowest levels) as a reference, after adjusting for multiple potential confounding factors, T3 layer (the highest levels) was independently associated with the occurrence of PSD (odds ratio [OR] = 2.639, 95% confidence interval [CI]: 1.317–5.287, P = 0.006). Similar results were found when the serum LCN2 was analyzed as a continuous variable. The optimal cut-off value of serum LCN2 at admission to predict PSD at discharge was 117.60ng/ml, at this threshold, the sensitivity was 77.2%, and the specificity was 53.4%.ConclusionsHigh serum LCN2 levels at admission are an independent risk factor for PSD in patients with AIS at discharge.

The role of T cells in acute ischemic stroke

Acute ischemic stroke (AIS) is associated with high rates of disability and mortality, exerting a substantial impact on overall survival and health-related quality of life. Treatment of AIS remains challenging given that the underlying pathologic mechanisms remain unclear. However, recent research has demonstrated that the immune system plays a key role in the development of AIS. Numerous studies have reported infiltration of T cells into ischemic brain tissue. While some types of T cells can promote the development of inflammatory responses and aggravate ischemic damage in patients with AIS, other T cells appear to exert neuroprotective effects via immunosuppression and other mechanisms. In this review, we discuss the recent findings regarding the infiltration of T cells into ischemic brain tissue, and the mechanisms governing how T cells can facilitate tissue injury or neuroprotection in AIS. Factors influencing the function of T cells, such as intestinal microflora and sex differences, are also discussed. We also explore the recent research on the effect of non-coding RNA on T cells after stroke, as well as the potential for specifically targeting T cells in the treatment of stroke patients.

Occurrence of Ischemic Stroke in Patients With Atrial Fibrillation Receiving Non-Vitamin K Oral Anticoagulants: Causes and Prevention Strategies.

Atrial fibrillation (AF) is a leading cause of cardioembolic stroke, which is often fatal or disabling. Prevention of stroke is crucial in AF management, and anticoagulation with non-vitamin K oral anticoagulants (NOACs) is the mainstay of AF management for stroke prevention. Because NOAC prescriptions have been surging worldwide, the development of acute ischemic stroke in patients with AF who receive NOAC treatment is an increasingly important issue in clinical practice. Moreover, these patients show a high risk of recurrence, with more than a 50% higher risk, than do patients with AF and no prior anticoagulation therapy. Careful evaluation is mandatory to determine possible causes of ischemic stroke during NOAC therapy. Differentiation of AF-unrelated stroke and demonstration of combined cardiac disease/systemic coagulopathy are important in these patients and may provide improved results in their treatment. In addition, ensuring appropriate dosing and good adherence to NOAC treatment is important. Cardioembolism, despite sufficient anticoagulation and no other causes, is the most common and challenging complication because switching to anticoagulants or adding antiplatelets to the treatment regimen does not reduce the risk of recurrent stroke, and there are no guidelines for this specific situation. This review article aimed to present the most updated data on the prevalence, causes, and secondary prevention strategies, specifically focusing on non-pharmacological approaches, together with relevant cases of AF in patients who developed ischemic stroke on NOAC therapy.

Elevated RANTES levels are associated with increased risk of cerebral atherosclerotic stenosis

BackgroundCerebral atherosclerotic stenosis (CAS) is a significant factor in the development of acute ischemic stroke (AIS). Previous studies have reported that cytokines are involved in atherosclerotic diseases, although the relationship between serum levels of the chemokine RANTES (regulated on activation, normal T-cell expressed and secreted) and the presence of CAS remains unclear.MethodsIn total, 127 participants (65 non-AIS controls and 62 patients with AIS) were involved in this study. CAS was defined as the presence of ≥ 50% stenosis in major intracranial or extracranial artery by a Digital Substraction Angiography (DSA) examination, and we classified all participants into four groups according to stroke and CAS status. Serum concentrations of 8 cytokines, including RANTES, were measured by the Human ProcartaPlex Multiplex Immunoassay Kit.ResultsSeventy-eight participants (61.41%) had CAS, of which 39 cases with AIS and 39 case with non-AIS. Patients with CAS had higher RANTES levels compared to non-CAS patients in both the non-AIS group (10.54 ± 0.80 vs. 13.20 ± 0.71, p = 0.016) and stroke group (11.96 ± 0.87 vs. 15.03 ± 0.75, p = 0.011), and multivariate logistic regression analysis showed that the RANTES level is independently associated with CAS in both the non-AIS group (adjusted odds ratio (OR), 1.07; 95% CI, 1.02–1.12, P = 0.004) and stroke group (adjusted OR, 1.32; 95% CI, 1.10–1.58, P = 0.003).ConclusionPatients with CAS have higher levels of serum RANTES than non-CAS patients regardless of stroke status suggesting that RANTES may play an important role in the formation of CAS.

Features of treatment and rehabilitation of COVID-19 patients with ischemic stroke

The development of COVID-19 is associated with damage to various organs and organ systems, including the development of acute ischemic stroke (AI). The article examines modern ideas about the pathogenesis of AI in COVID-19. The data on the choice of optimal therapy for patients with acute AI and COVID-19, as well as on the possibility of improving the effectiveness of rehabilitation measures, are analyzed. Information is provided on the efficacy of the drug Mexidol in patients with AI and COVID-19.

Longitudinal Change of Serum Inter-α-Trypsin Inhibitor Heavy Chain H4 and its Relation with Inflammation, Disease Recurrence, and Mortality in Acute Ischemic Stroke Patients.

Inter-α-trypsin inhibitor heavy chain H4 (ITIH4) modulates atherosclerosis, lipid, and inflammation, which is involved in the development of acute ischemic stroke. Hence, this study aimed to investigate the longitudinal change and prognostic role of ITIH4 in acute ischemic stroke. In 267 patients with acute ischemic stroke, serum ITIH4 after admission (baseline), the 1st day after admission (D1), D3, D7, and D30, and inflammatory cytokines at baseline were detected by enzyme-linked immunosorbent assay (ELISA). Additionally, serum ITIH4 of 30 controls after enrollment was detected by ELISA. ITIH4 was reduced in acute ischemic stroke patients than controls [median (interquartile range, IQR): 131.0 (95.5-194.3) vs. 418.6 (241.5-506.8) ng/mL] (P < 0.001). Among acute ischemic stroke patients, ITIH4 was negatively associated with tumor necrosis factor-alpha (r = -0.211, P = 0.001), interleukin (IL)-1β (r = -0.164, P = 0.007), IL-6 (r = -0.121, P = 0.049), and IL-17A (r = -0.188, P = 0.002). ITIH4 presented a decreased trend from admission to D3, then increased from D3 to D30 (P < 0.001). The 1-year, 2-year, and 3-year cumulative recurrence rate was 7.5%, 18.0%, and 19.1%, respectively; meanwhile, 1-year, 2-year, and 3-year cumulative death rate was 2.2%, 7.1%, and 7.1%, accordingly. The further analysis presented that ITIH4 at baseline (P = 0.002), D1 (P = 0.049), D3 (P = 0.003), D7 (P < 0.001), and D30 (P < 0.001) was decreased in recurrent patients than non-recurrent patients; besides, ITIH4 at D3 (P = 0.017), D7 (P = 0.004), and D30 (P = 0.002), but not at baseline (P = 0.151) or D1 (P = 0.013), was decreased in deaths than survivors. Serum ITIH4 declines at first and then elevates with time, and its reduction is correlated with higher inflammation, increased risk of recurrence and mortality in acute ischemic stroke patients.