Function of miR-21-5p derived from ADSCs-exos on the neuroinflammation after cerebral ischemia.

INTRODUCTION: Cerebral ischemia (CI) induces a profound neuroinflammatory response, but the underlying molecular mechanism remains unclear. Exosomes from adipose-derived stem cells (ADSC-exos) have been found to play a crucial role in cell communication by transferring molecules including microRNAs (miRNAs), which have been shown to modulate the inflammatory response after CI and are viable molecular targets for altering brain function. The current study aimed to explore the contribution of ADSC-exosomal miR-21-5p to the neuroinflammation after CI. METHODS: The differentially expressed miR-21-5p in CI was screened based on literature search. The target mRNAs of miR-21-5p were predicted using online databases and verified by luciferase reporter assay. Then, BV2 cells were treated with hemin to simulate the inflammatory response after CI, and its animal model was induced using the MCAO method. Ischemia was evaluated in rats using 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining. ADSCs-exos were further isolated and identified by western blot analysis and transmission electron microscope. RESULTS: MiR-21-5p was significantly down-regulated in CI and alleviated neuropathic damage after CI by the PIK3R1/PI3K/AKT signaling axis. And miR-21-5p derived from ADSCs-exos alleviated neuroinflammation after CI via promoting microglial M2 polarization. CONCLUSION: We demonstrated that ADSC-exosomal miR-21-5p mitigated post-CI inflammatory response through the PIK3R1/PI3K/AKT signaling axis and could offer neuroprotection after CI through promoting polarization of M2 microglia.

Peripheral blood syndecan-1 levels after mechanical thrombectomy can predict the clinical prognosis of patients with acute ischemic stroke.

BACKGROUND: Previously, we revealed noticeable dynamic fluctuations in syndecan-1 levels in the peripheral blood of post-stroke patients. We further investigated the clinical prognostic value of syndecan-1 as a biomarker of glycoprotein damage in patients with acute ischaemic stroke (AIS). METHODS: We examined 105 patients with acute large vessel occlusion in the anterior circulation, all of whom underwent mechanical thrombectomy (MT). Peripheral blood syndecan-1 levels were measured 1 day after MT, and patients were categorised into favourable and unfavourable prognostic groups based on the 90-day modified Rankin Scale (mRS) score. Additionally, we compared the clinical outcomes between groups with high and low syndecan-1 concentrations. RESULTS: The findings revealed a significantly lower syndecan-1 level in the group with an unfavourable prognosis compared to those with a favourable prognosis (p < 0.01). In the multivariable logistic regression analysis, lower syndecan-1 levels were identified as a predictor of unfavourable prognosis (odds ratio (OR) = 0.965, p = 0.001). Patients displaying low syndecan-1 expression in the peripheral blood (< 29.51 ng/mL) experienced a > twofold increase in the rates of unfavourable prognosis and mortality. CONCLUSIONS: Our study demonstrates that syndecan-1, as an emerging, easily detectable stroke biomarker, can predict the clinical outcomes of patients with AIS. After MT, low levels of syndecan-1 in the peripheral blood on the first day emerged as an independent risk factor for an unfavourable prognosis, suggesting that lower syndecan-1 levels might signify worse clinical presentation and outcomes in stroke patients undergoing this procedure.

Integrate prediction of machine learning for single ACoA rupture risk: a multicenter retrospective analysis.

Background: Statistically, Anterior communicating aneurysm (ACoA) accounts for 30 to 35% of intracranial aneurysms. ACoA, once ruptured, will have an acute onset and cause severe neurological dysfunction and even death. Therefore, clinical analysis of risk factors related to ACoA and the establishment of prediction model are the benefits to the primary prevention of ACoA. Methods: Among 1,436 cases of single ACoA patients, we screened 1,325 valid cases, classified risk factors of 1,124 cases in the ruptured group and 201 cases in the unruptured group, and assessed the risk factors, respectively, and predicted the risk of single ACoA rupture by using the logistic regression and the machine learning. Results: In the ruptured group (84.8%) of 1,124 cases and the unruptured group (15.2%) of 201 cases, the multivariable logistic regression (MLR) model shows hemorrhagic stroke history (OR 95%CI, p:0.233 (0.120-0.454),<0.001) and the age stratification of 60-69 years (OR 95%CI, p:0.425 (0.271-0.668),<0.001) has a significant statistic difference. In the RandomForest (RF) model, hemorrhagic stroke history and age are the best predictive factors. Conclusion: We combined the analysis of MLR, RF, and PCA models to conclude that hemorrhagic stroke history and gender affect single ACoA rupture. The RF model with web dynamic nomogram, allows for real-time personalized analysis based on different patients' conditions, which is a tremendous advantage for the primary prevention of single ACoA rupture. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=178501.

Mechanical thrombectomy via direct carotid artery approach for the treatment of acute anterior circulation large vessel occlusion.

Background: Mechanical thrombectomy (MT) has become an important treatment method for acute anterior circulation large vessel occlusion. The carotid artery approach is a fast and effective alternative when the transfemoral approach is difficult due to vascular variation. The present study reports on seven cases of acute anterior circulation stroke where direct carotid approach was used to obtain vascular access. Methods and materials: Patients with acute anterior circulation large vessel occlusion treated via carotid artery access between January 2018 and January 2020 were retrospectively analyzed. Brain computed tomography (CT) and angiographic imaging results, indications for carotid artery approach and technical aspects of the method, modified thrombolysis in cerebral infarction (mTICI), procedure-related complications, and patient outcomes were evaluated. Results: Seven patients were treated using a direct carotid artery approach. Among the seven cases, four patients were treated using percutaneous carotid artery puncture, and two patients were treated with emergency carotid artery incision and thrombectomy. The remaining case involved carotid artery puncture for MCA thrombectomy, followed by carotid artery incision for carotid artery thrombectomy. The carotid artery puncture point was exposed via surgical incision and sutured after MT. Modified Rankin Scale (MRS) scores 90 days after surgery showed good prognosis in three patients, poor prognosis in four patients. Conclusion: This case series highlights the advantage of using a transcarotid approach to bypass anatomical barriers to achieve faster reperfusion when the femoral approach is not possible. The carotid artery puncture point was surgically exposed and sutured to reduce the incidence of postoperative complications.

Unilateral contrast-induced encephalopathy with contrast medium exudation: A case report.

BACKGROUND: Contrast-induced encephalopathy (CIE) is a rare transient, reversible abnormality in the structure or function of the nervous system caused by the intravascular use of contrast agents. CIE can present with a range of neurological manifestations, including focal neurological deficits (hemiplegia, hemianopia, cortical blindness, aphasia, and parkinsonism) and systemic symptoms (confusion, seizures, and coma). However, if not accurately diagnosed and treated in a timely manner, CIE can cause irreversible damage to patients, especially critically ill patients. CASE SUMMARY: A male in his 50 s, 2 h after digital subtraction angiography, had a progressive disorder of consciousness, mixed aphasia, bilateral pupillary sluggish light reflex, and right limb weakness. Seven hours after the procedure, he developed unconsciousness, high fever (39.5 °C), seizures, hemiplegia, neck stiffness (+), and right Babinski signs (+). computed tomography (CT) findings 2 h postprocedure were very confusing and led us to misdiagnose the patient with subarachnoid hemorrhage. Brain CT was performed again 7 h after the procedure. Compared with the CT 2 h after the procedure, the CT 7 h after the procedure showed that the manifestations of subarachnoid hemorrhage in the left cerebral hemisphere had disappeared and were replaced by brain tissue swelling, and the cerebral sulci had disappeared. Combined with the clinical manifestations of the patient and after the exclusion of subarachnoid hemorrhage and cerebrovascular embolism, we diagnosed the patient with CIE, and intravenous fluids were given for adequate hydration, as well as mannitol, albumin dehydration, furosemide and the glucocorticoid methylprednisolone. After 17 d of active treatment, the patient was discharged with no sequelae. CONCLUSION: CIE should be taken seriously, but it is easily misdiagnosed, and once CIE is diagnosed, rapid, accurate diagnosis and treatment are critical steps. Whether a follow-up examination using a contrast agent can be performed should be closely evaluated, and the patient should be fully informed of the associated risks.

Thrombosis origin identification of cardioembolism and large artery atherosclerosis by distinct metabolites.

BACKGROUND: The diagnosis of cerebral thrombosis origin is challenging and remains unclear. This study aims to identify thrombosis due to cardioembolism (CE) and large artery atherosclerosis (LAA) from a new perspective of distinct metabolites. METHODS: Distinct metabolites between 26 CE and 22 LAA origin thrombi, which were extracted after successful mechanical thrombectomy in patients with acute ischemic stroke in the anterior circulation, were analyzed with a ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) system. Enriched metabolic pathways related to the metabolites were identified. Least absolute shrinkage selection operator regression analyses and a filtering method were used to select potential predictors. Furthermore, four machine learning classifiers, including decision tree, logistic regression, random forest (RF), and k means unsupervised classification model, were used to evaluate the predictive ability of the selected metabolites. RESULTS: UPLC-QTOF-MS analysis revealed that levels of 88 and 55 metabolites were elevated in LAA and CE thrombi, respectively. Kyoto Encyclopedia of Genes and Genomes analysis revealed a significant difference between the pathways enriched in the two types of thrombi. Six metabolites (diglyceride (DG, 18:3/24:0), DG (22:0/24:0), phytosphingosine, galabiosylceramide (18:1/24:1), triglyceride (15:0/16:1/o-18:0), and glucosylceramide (18:1/24:0)) were finally selected to build a predictive model. The predictive RF model was confirmed to be the best, with a satisfactory stability and prediction capacity (area under the curve=0.889). CONCLUSIONS: Six metabolites as potential predictors for distinguishing between cerebral thrombi of CE and LAA origin were identified. The results are useful for understanding the pathogenesis and for secondary stroke prevention.

Characteristics of the gut microbiota of patients with symptomatic carotid atherosclerotic plaques positive for bacterial genetic material.

Background: The gut microbiota (GM) is believed to be closely associated with symptomatic carotid atherosclerosis (SCAS), yet more evidence is needed to substantiate the significant role of GM in SCAS. This study, based on the detection of bacterial DNA in carotid plaques, explores the characteristics of GM in SCAS patients with plaque bacterial genetic material positivity, aiming to provide a reference for subsequent research. Methods: We enrolled 27 healthy individuals (NHF group) and 23 SCAS patients (PFBS group). We utilized 16S rDNA V3-V4 region gene sequencing to analyze the microbiota in fecal samples from both groups, as well as in plaque samples from the carotid bifurcation extending to the origin of the internal carotid artery in all patients. Results: Our results indicate significant differences in the gut microbiota (GM) between SCAS patients and healthy individuals. The detection rate of bacterial DNA in plaque samples was approximately 26%. Compared to patients with negative plaques (PRSOPWNP group), those with positive plaques (PRSOPWPP group) exhibited significant alterations in their GM, particularly an upregulation of 11 bacterial genera (such as Klebsiella and Streptococcus) in the gut, which were also present in the plaques. In terms of microbial gene function prediction, pathways such as Fluorobenzoate degradation were significantly upregulated in the GM of patients with positive plaques. Conclusion: In summary, our study is the first to identify significant alterations in the gut microbiota of patients with positive plaques, providing crucial microbial evidence for further exploration of the pathogenesis of SCAS.

Thirty-six months recurrence after acute ischemic stroke among patients with comorbid type 2 diabetes: A nested case-control study.

Background: Stroke patients have to face a high risk of recurrence, especially for those with comorbid T2DM, which usually lead to much more serious neurologic damage and an increased likelihood of death. This study aimed to explore determinants of stroke relapse among patients with comorbid T2DM. Materials and methods: We conducted this case-control study nested a prospective cohort of ischemic stroke (IS) with comorbid T2DM. During 36-month follow-up, the second stroke occurred in 84 diabetic IS patients who were allocated into the case group, while 613 patients without recurrence were the controls. We collected the demographic data, behaviors and habits, therapies, and family history at baseline, and measured the variables during follow-up. LASSO and Logistic regression analyses were carried out to develop a prediction model of stroke recurrence. The receiver operator characteristic (ROC) curve was employed to evaluate the performance of the prediction model. Results: Compared to participants without recurrence, the higher levels of pulse rate (78.29 ± 12.79 vs. 74.88 ± 10.93) and hypertension (72.6 vs. 61.2%) were recorded at baseline. Moreover, a lower level of physical activity (77.4 vs. 90.4%), as well as a higher proportion of hypoglycemic therapy (36.9 vs. 23.3%) was also observed during 36-month follow-up. Multivariate logistic regression revealed that higher pulse rate at admission (OR = 1.027, 95 %CI = 1.005-1.049), lacking physical activity (OR = 2.838, 95% CI = 1.418-5.620) and not receiving hypoglycemic therapy (OR = 1.697, 95% CI = 1.013-2.843) during follow-up increased the risk of stroke recurrence. We developed a prediction model using baseline pulse rate, hypoglycemic therapy, and physical activity, which produced an area under ROC curve (AUC) of 0.689. Conclusion: Physical activity and hypoglycemic therapy play a protective role for IS patients with comorbid diabetes. In addition to targeted therapeutics, the improvement of daily-life habit contributes to slowing the progress of the IS.

Acute Ischemic Stroke Comorbid with Type 2 Diabetes: Long-Term Prognosis Determinants in a 36-Month Prospective Study for Personalized Medicine.

Ischemic stroke (IS) is often comorbid with type 2 diabetes mellitus (T2DM) wherein the determinants of long-term outcomes, beyond the acute stroke phase, are not adequately known. This study identified the determinants of long-term outcomes for diabetic IS patients through a prospective nested case-control study in 624 patients treated with conservative measures (38.60% females, mean age: 63.85 years). After 36-month follow-up, 117 (18.8%) patients with poor outcome were enrolled in the case group. The poor outcome was defined with a modified Rankin Scale (mRS) score ≥3. Meanwhile, 374 (59.9%) patients with good outcome, defined as (mRS score <3), were included in the control group. Patients who died (n = 32) or lost to follow-up (n = 101) were excluded in analysis. Poor prognostic outcome was positively associated with (1) the pulse rate at admission, (2) diastolic blood pressure (DBP), and (3) fasting blood glucose (FBG) during follow-up, whereas physical activity and lipid-lowering treatment during follow-up were negatively associated. Importantly, a forecasting model with these indicators distinguished the patients with good versus poor outcomes with 70.1% sensitivity and 73.5% specificity. Health care professionals and laboratory medicine scholars may want to monitor an increase in DBP and FBG during follow-up, as well as physical activity and lipid-lowering treatment, in relationship to the prognosis of IS with comorbid T2DM after conservative therapies. The proposed predictive model for personalized/precision medicine requires field testing in independent studies, and might help risk stratification with theranostic tests for patients with acute IS who also have a diagnosis of T2DM.

Plasma Lipid Mediators Associate With Clinical Outcome After Successful Endovascular Thrombectomy in Patients With Acute Ischemic Stroke.

Background: Neuroinflammatory response contributes to early neurological deterioration (END) and unfavorable long-term functional outcome in patients with acute ischemic stroke (AIS) who recanalized successfully by endovascular thrombectomy (EVT), but there are no reliable biomarkers for their accurate prediction. Here, we sought to determine the temporal plasma profiles of the bioactive lipid mediators lipoxin A4 (LXA4), resolvin D1 (RvD1), and leukotriene B4 (LTB4) for their associations with clinical outcome. Methods: We quantified levels of LXA4, RvD1, and LTB4 in blood samples retrospectively and longitudinally collected from consecutive AIS patients who underwent complete angiographic recanalization by EVT at admission (pre-EVT) and 24 hrs post-EVT. The primary outcome was unfavorable long-term functional outcome, defined as a 90-day modified Rankin Scale score of 3-6. Secondary outcome was END, defined as an increase in National Institutes of Health Stroke Scale (NIHSS) score ≥4 points at 24 hrs post-EVT. Results: Eighty-one consecutive AIS patients and 20 healthy subjects were recruited for this study. Plasma levels of LXA4, RvD1, and LTB4 were significantly increased in post-EVT samples from AIS patients, as compared to those of healthy controls. END occurred in 17 (20.99%) patients, and 38 (46.91%) had unfavorable 90-day functional outcome. Multiple logistic regression analyses demonstrated that post-EVT levels of LXA4 (adjusted odd ratio [OR] 0.992, 95% confidence interval [CI] 0.987-0.998), ΔLXA4 (adjusted OR 0.995, 95% CI 0.991-0.999), LTB4 (adjusted OR 1.003, 95% CI 1.001-1.005), ΔLTB4 (adjusted OR 1.004, 95% CI 1.002-1.006), and post-EVT LXA4/LTB4 (adjusted OR 0.023, 95% CI 0.001-0.433) and RvD1/LTB4 (adjusted OR 0.196, 95% CI 0.057-0.682) ratios independently predicted END, and post-EVT LXA4 levels (adjusted OR 0.995, 95% CI 0.992-0.999), ΔLXA4 levels (adjusted OR 0.996, 95% CI 0.993-0.999), and post-EVT LXA4/LTB4 ratio (adjusted OR 0.285, 95% CI 0.096-0.845) independently predicted unfavorable 90-day functional outcome. These were validated using receiver operating characteristic curve analyses. Conclusions: Plasma lipid mediators measured 24 hrs post-EVT were independent predictors for early and long-term outcomes. Further studies are needed to determine their causal-effect relationship, and whether the imbalance between anti-inflammatory/pro-resolving and pro-inflammatory lipid mediators could be a potential adjunct therapeutic target.

CRISPR Detection and Research on Screening Mutant Gene TTN of Moyamoya Disease Family Based on Whole Exome Sequencing.

Moyamoya disease (MMD) has a high incidence in Asian populations and demonstrates some degree of familial clustering. Whole-exome sequencing (WES) is useful in establishing key related genes in familial genetic diseases but is time-consuming and costly. Therefore, exploring a new method will be more effective for the diagnosis of MMD. We identified familial cohorts showing MMD susceptibility and performed WES on 5 affected individuals to identify susceptibility loci, which identified point mutation sites in the titin (TTN) gene (rs771533925, rs559712998 and rs72677250). Moreover, TTN mutations were not found in a cohort of 50 sporadic MMD cases. We also analyzed mutation frequencies and used bioinformatic predictions to reveal mutation harmfulness, functions and probabilities of disease correlation, the results showed that rs771533925 and rs72677250 were likely harmful mutations with GO analyses indicating the involvement of TTN in a variety of biological processes related to MMD etiology. CRISPR-Cas12a assays designed to detect TTN mutations provided results consistent with WES analysis, which was further confirmed by Sanger sequencing. This study recognized TTN as a new familial gene marker for moyamoya disease and moreover, demonstrated that CRISPR-Cas12a has the advantages of rapid detection, low cost and simple operation, and has broad prospects in the practical application of rapid detection of MMD mutation sites.

Development of bilateral subdural hematoma after endovascular embolization of a dural sinus malformation.

INTRODUCTION: Dural sinus malformation is a rare congenital malformation characterized by a remarkable dilated dural sinus pouch. We described the development of bilateral subdural hematoma after endovascular embolization of a dural sinus malformation in an infant. CASE DESCRIPTION: A 32-day male infant was observed to have a fever and enlarged head circumference. A dural sinus malformation with giant dural sinus pouch thrombosis was established by magnetic resonance imaging and digital subtraction angiography. The patient developed bilateral subdural hematoma after endovascular embolization of the dural fistula. His neurological outcome was normal at 3-year follow-up. CONCLUSION: We report a case of development of bilateral subdural hematoma after endovascular embolization of a dural sinus malformation and had a normal neurological outcome.

Identification of key pathways and genes in carotid atherosclerosis through bioinformatics analysis of RNA-seq data.

While acknowledging carotid atherosclerosis (CAS) as a risk factor for ischemic stroke, reports on its pathogenesis are scarce. This study aimed to explore the potential mechanism of CAS through RNA-seq data analysis. Carotid intima tissue samples from CAS patients and healthy subjects were subjected to RNA-seq analysis, which yielded, 1,427 differentially expressed genes (DEGs) related to CAS. Further, enrichment analysis (Gene Ontology, KEGG pathway, and MOCDE analysis) was performed on the DEGs. Hub genes identified via the protein-protein interaction network (PPI) were then analyzed using TRRUST, DisGeNET, PaGenBase, and CMAP databases. Results implicated inflammation and immunity in the pathogenesis of CAS. Also, lung disease was associated with CAS. Hub genes were expressed in multiple diseases, mainly regulated by RELA and NFKB1. Moreover, three small-molecule compounds were found via the CMAP database for management of CAS; hub genes served as potential targets. Collectively, inflammation and immunity are the potential pathological mechanisms of CAS. This study implicates CeForanide, Chenodeoxycholic acid, and 0317956-0000 as potential drug candidates for CAS treatment.

Annexin A1 protects against cerebral ischemia-reperfusion injury by modulating microglia/macrophage polarization via FPR2/ALX-dependent AMPK-mTOR pathway.

BACKGROUND: Cerebral ischemia-reperfusion (I/R) injury is a major cause of early complications and unfavorable outcomes after endovascular thrombectomy (EVT) therapy in patients with acute ischemic stroke (AIS). Recent studies indicate that modulating microglia/macrophage polarization and subsequent inflammatory response may be a potential adjunct therapy to recanalization. Annexin A1 (ANXA1) exerts potent anti-inflammatory and pro-resolving properties in models of cerebral I/R injury. However, whether ANXA1 modulates post-I/R-induced microglia/macrophage polarization has not yet been fully elucidated. METHODS: We retrospectively collected blood samples from AIS patients who underwent successful recanalization by EVT and analyzed ANXA1 levels longitudinally before and after EVT and correlation between ANXA1 levels and 3-month clinical outcomes. We also established a C57BL/6J mouse model of transient middle cerebral artery occlusion/reperfusion (tMCAO/R) and an in vitro model of oxygen-glucose deprivation and reoxygenation (OGD/R) in BV2 microglia and HT22 neurons to explore the role of Ac2-26, a pharmacophore N-terminal peptide of ANXA1, in regulating the I/R-induced microglia/macrophage activation and polarization. RESULTS: The baseline levels of ANXA1 pre-EVT were significantly lower in 23 AIS patients, as compared with those of healthy controls. They were significantly increased to the levels found in controls 2-3 days post-EVT. The increased post-EVT levels of ANXA1 were positively correlated with 3-month clinical outcomes. In the mouse model, we then found that Ac2-26 administered at the start of reperfusion shifted microglia/macrophage polarization toward anti-inflammatory M2-phenotype in ischemic penumbra, thus alleviating blood-brain barrier leakage and neuronal apoptosis and improving outcomes at 3 days post-tMCAO/R. The protection was abrogated when mice received Ac2-26 together with WRW4, which is a specific antagonist of formyl peptide receptor type 2/lipoxin A4 receptor (FPR2/ALX). Furthermore, the interaction between Ac2-26 and FPR2/ALX receptor activated the 5' adenosine monophosphate-activated protein kinase (AMPK) and inhibited the downstream mammalian target of rapamycin (mTOR). These in vivo findings were validated through in vitro experiments. CONCLUSIONS: Ac2-26 modulates microglial/macrophage polarization and alleviates subsequent cerebral inflammation by regulating the FPR2/ALX-dependent AMPK-mTOR pathway. It may be investigated as an adjunct strategy for clinical prevention and treatment of cerebral I/R injury after recanalization. Plasma ANXA1 may be a potential biomarker for outcomes of AIS patients receiving EVT.

Reliability assessment on intravascular photoacoustic imaging of lipid: ex vivo animal and human sample validation.

Although the lipid-detecting IVPA imaging system has been developed in resolution, speed, and catheter size, there is no parameterization study of the reliability on the IVPA imaging for lipid diagnosis. Here, the sensitivity, specificity, and accuracy were calculated to assess the reliability of the IVPA imaging of lipid. Abdominal aortas from six rabbits with atherosclerosis, were subjected to the IVPA imaging and Oil Red O staining, and 75 groups of IVPA as well as corresponding histological images were obtained. Similarly, 125 groups of IVPA and histological results were obtained from five human carotid plaque samples. The sensitivity, specificity, and accuracy, calculated from the statistical data, were 96.8%, 83.3%, 94.6% and 97.3%, 72.7%, 95.2%, respectively. The numerical values of sensitivity, specificity, and accuracy demonstrated the reliability of IVPA imaging on distinguishing the lesions vessel with lipid-rich plaque, which provided the foundation for IVPA translation to clinical application.

Beneficial consequences of Lupeol on middle cerebral artery-induced cerebral ischemia in the rat involves Nrf2 and P38 MAPK modulation.

Lupeol has been reported to exhibit anti-inflammatory and anti-tumor activities in many diseases, but its potential effects in cerebral ischemia injury have not been studied to date. In this work we present evidence for a beneficial effect of lupeol in a rat model of middle cerebral artery occlusion (MCAO) followed by reperfusion (MCAO/R) injury and provide some histological and biochemical evidence for its mechanism of action. A cerebral MCAO rat model was established by vascular occlusion for 2 h, followed by 24 h reperfusion period. The infarct volume, neurological deficits, and brain water content were compared with animals treated during reperfusion with different concentrations of lupeol. Macroscopic parameters, cell viability, pro-inflammatory factors generation, as well as oxidative stress parameters and associated apoptotic signaling cascades were evaluated. Treatment with lupeol significantly reduced the cerebral infarct volume and water content and recovered neuro behavioral functions in affected rats. Lupeol treatment down-regulated the expression of oxidative stress and inflammation factors. In addition, lupeol activated Nrf2, suppressed caspase-3 activity, reduced BAX/Bcl-2 ratio and inhibited phosphorylation of p38 MAPK. The data suggest that lupeol may exert protective effects against cerebral ischemia by suppressing oxidative stress and reduction of inflammation factors possible via activation of nuclear transcription factors and inhibition of cell death pathways.

Combined surgical and interventional treatment of tandem carotid artery and middle cerebral artery embolus: A case report.

BACKGROUND: The 2018 American Heart Association/American Stroke Association guidelines for early management of acute ischemic stroke recommend the use of retrievable stents for mechanical thrombectomy in patients with acute internal carotid artery or middle cerebral artery M1 occlusion that can be treated within 6 h from onset. For cases of carotid artery with ipsilateral middle cerebral artery tandem embolization, the operation is more complicated and challenging. We here report a case of a tandem embolism, and the anatomy of the aortic arch was complex. Direct carotid artery incision and thrombectomy can not only prevent the escape of the carotid embolus but also save time during establishment of the thrombectomy access. CASE SUMMARY: The patient was a 70-year-old man. He was admitted to hospital due to sudden inability to speak and inability to move his right limb for 3 h. Imaging confirmed a diagnosis of a tandem embolism in the left carotid artery with left M1 occlusion. Carotid artery incision thrombectomy combined with stent thrombectomy was performed. The operation was successful, and 24 h later the patient was conscious and mentally competent but had motor aphasia. His bilateral limb muscle strength level was 5, and his neurologic severity scores score was 2. CONCLUSION: Carotid artery incision thrombectomy combined with stenting for carotid artery plus cerebral artery tandem embolization is clinically feasible. For patients with a complicated aortic arch and an extremely tortuous carotid artery, carotid artery incision can be chosen to establish the interventional path.

Upregulation of microRNA-206 induces apoptosis of vascular smooth muscle cells and decreases risk of atherosclerosis through modulating FOXP1.

Forkhead box protein subfamily P (FOXP) 1 has an important role in the control of gene transcription and is also reported to function as a tumor suppressor. The aim of the present study was to explore the regulatory mechanisms of atherosclerosis by investigating the function of microRNA-206 (miR-206) and the regulatory association between miR-206 and its potential target gene, FOXP1, in vascular smooth muscle cells (VSMCs). Bioinformatics tools were utilized to identify FOXP1 as a target of miR-206. Luciferase reporter analysis was used to confirm this relationship and to identify the miR-206 binding site in the FOXP1 3'-untranslated region. It was demonstrated that the relative survival rate of VSMCs was suppressed by miR-206 compared with scramble controls. Furthermore, reduced expression of miR-206 in atherosclerosis tissue samples was observed, and the mRNA and protein expression levels of FOXP1 were upregulated in atherosclerosis tissue samples, both compared with the controls, indicating a negative correlation between miR-206 and FOXP1. Additionally, when treated with miR-206 mimics, the relative survival rate of VSMCs was notably reduced, which was rescued by overexpression of FOXP1. These findings increased the understanding of the regulatory role of miR-206 in atherosclerosis in VSMCs via targeting the FOXP1 gene; therefore, intervention with miR-206 as a therapeutic technique may be a strategy for atherosclerosis treatment in the future.

Surgical Revascularization of Symptomatic Kinking of the Internal Carotid Artery.

OBJECTIVE: To evaluate the safety and outcomes of surgical revascularization for patients with symptomatic kinking of the internal carotid artery (ICA). METHODS: Twenty-five consecutive patients presented with symptomatic kinking of the ICA and a history of transient ischemic attack (TIA) or stroke were prospectively enrolled in this study. All patients were treated with ICA transection and end-to-side reimplantation at the level of the carotid bulb. Patients were followed up for a median of 32 months. RESULTS: There were no deaths or strokes within the 30 days of the treatment. No postprocedural thrombosis or narrowing of the ipsilateral ICA was observed. One (4%) patient had temporary recurrent nerve palsy, which was completely recovered at 4-week follow-up. One (4%) patient had a myocardial ischemic event. At the end of the 32-month follow-up, 1 (4%) patient developed ipsilateral minor stroke. No recurrent stenosis was detected by Doppler ultrasound. CONCLUSION: Surgical treatment for isolated, symptomatic kinking of the ICA and a history of TIA or stroke is safe, and the outcomes are acceptable.