The role of OPA1-related mitochondrial fusion in brain reperfusion stress has remained elusive. The aim of our study is to explore whether melatonin alleviates cerebral IR injury by modulating ...OPA1-related mitochondrial fusion. We found that melatonin reduced infarct area and suppressed neuron death during reperfusion stress. Biological studies have revealed that IR-inhibited mitochondrial fusion was largely reversed by melatonin via upregulated OPA1 expression. Knocking down OPA1 abrogated the protective effects of melatonin on mitochondrial energy metabolism and mitochondrial apoptosis. In addition, we also found that melatonin modified OPA1 expression via the Yap-Hippo pathway; blockade of the Yap-Hippo pathway induced neuron death and mitochondrial damage despite treatment with melatonin. Altogether, our data demonstrated that cerebral IR injury is closely associated with defective OPA1-related mitochondrial fusion. Melatonin supplementation enhances OPA1-related mitochondrial fusion by activating the Yap-Hippo pathway, ultimately reducing brain reperfusion stress.
We aimed to establish the prevalence, characteristics, and outcomes of intracranial atherosclerosis (ICAS) in China by a large, prospective, multicenter study.
We evaluated 2864 consecutive patients ...who experienced an acute cerebral ischemia<7 days after symptom onset in 22 Chinese hospitals. All patients underwent magnetic resonance angiography, with measurement of diameter of the main intracranial arteries. ICAS was defined as ≥50% diameter reduction on magnetic resonance angiography.
The prevalence of ICAS was 46.6% (1335 patients, including 261 patients with coexisting extracranial carotid stenosis). Patients with ICAS had more severe stroke at admission and stayed longer in hospitals compared with those without intracranial stenosis (median National Institutes of Health Stroke Scale score, 3 versus 5; median length of stay, 14 versus 16 days; both P<0.0001). After 12 months, recurrent stroke occurred in 3.27% of patients with no stenosis, in 3.82% for those with 50% to 69% stenosis, in 5.16% for those with 70% to 99% stenosis, and in 7.27% for those with total occlusion. Cox proportional hazards regression analyses showed that the degree of arterial stenosis, age, family history of stroke, history of cerebral ischemia or heart disease, complete circle of Willis, and National Institutes of Health Stroke Scale score at admission were independent predictors for recurrent stroke at 1 year. The highest rate of recurrence was observed in patients with occlusion with the presence of ≥3 additional risk factors.
ICAS is the most common vascular lesion in patients with cerebrovascular disease in China. Recurrent stroke rate in our study was lower compared with those of previous clinical trials but remains unacceptably high in a subgroup of patients with severe stenosis.
Early recanalization after endovascular treatment could improve the prognosis of acute ischemia stroke. Futile recanalization often occurred which was one of the main causes of failure. By now the ...mechanisms of futile recanalization were not clear. They are probably concerned with bad collateral circulation, subacute reocclusion, large hypoperfusion volumes, microvascular compromise, and impaired cerebral autoregulation. Previous research found that some of the image markers could be used as the accurate predictors for poor prognosis after successful treatment in order to identify the patients who were not suitable for recanalization and reduce some of the unnecessary cost. Predictors for futile recanalization mentioned in our article can be used for supplement to make decision for endovascular treatment.
Background:
Hyperglycemia has been considered a predictor of stroke outcomes. In this article we study the correlation between blood glucose levels within the first 24 h after stroke onset and ...patients’ outcomes in mortality and hemorrhagic transformations.
Methods:
Ninety-one non-diabetic patients with acute ischemic stroke admitted to a neurological intensive unit were recruited. Their blood glucose was measured twice within 6 h (baseline) and at every hour after stroke onset. Patients were collected into four groups as follows: those in which normoglycemia and no hyperglycemia were observed at either baseline or 24 h; those with baseline hyperglycemia and hyperglycemia only at baseline; those with 24 h hyperglycemia and hyperglycemia only at 24 h after stroke; and those with persistent hyperglycemia and hyperglycemia at both baseline and at 24 h. Endpoints were designated as the patient’s death within 30 days and/or hemorrhagic transformation under computerized tomography within the first 7 days after stroke onset.
Results:
Persistent hyperglycemia was correlated with an increased risk of mortality within 30 days (OR = 24.0; 95% CI = 2.8–199.3) and it was also correlated with hemorrhagic transformation (OR = 13.3; 95% CI = 2.7–66.1). Baseline or delayed hyperglycemia were not correlated with any outcome.
Conclusions:
Persistent hyperglycemia was correlated with mortality after acute ischemic stroke.
Cerebral recanalization therapy, either intravenous thrombolysis or mechanical thrombectomy, improves the outcomes in patients with acute ischemic stroke (AIS) by restoring the cerebral perfusion of ...the ischemic penumbra. Cerebral hemodynamic evaluation after recanalization therapy, can help identify patients with high risks of reperfusion-associated complications. Among the various hemodynamic modalities, magnetic resonance imaging (MRI), computed tomography perfusion, and transcranial Doppler sonography (TCD) are the most commonly used. Poststroke hypoperfusion is associated with infarct expansion, while hyperperfusion, which once was considered the hallmark of successful recanalization, is associated with hemorrhagic transformation. Either the hypo- or the hyperperfusion may result in poor clinical outcomes. Individual blood pressure target based on cerebral hemodynamic evaluation was crucial to improve the prognosis. This review summarizes literature on cerebral hemodynamic evaluation and management after recanalization therapy to guide clinical decision making.
Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition with high disability and mortality. MicroRNAs (miRNAs) are reported to play a modulating role in aSAH. We investigated ...specific plasma microRNAs (miRNAs) associated with aSAH and gained comprehensive insight into its pathological mechanisms.
This is a prospective case-control study. We used a two-stage approach, with primary screening and ensuing two-step validation stages. Significantly differentially expressed plasma miRNAs between aSAH patients and neurologically healthy controls were initially screened by microarray analysis. These miRNAs were then validated in two groups of independent cohorts using reverse transcription quantitative real-time polymerase chain reaction assays. Functional annotation of these miRNA targets was performed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses.
In the primary screening stage, 14 miRNAs were identified as differentially expressed at a significance level of
< 0.05 and fold change >2 between 5 aSAH patients and 5 neurologically healthy controls. In the two validation steps (20 patients vs. 20 control; 40 patients vs. 30 controls), miR-23b-3p, miR-590-5p, miR-20b-5p, miR-142-3p, and miR-29b-3p were found to be significantly down-regulated in patients with aSAH compared with controls. Through these 5 miRNAs, we obtained 32 overlapping target genes, including TGM2, EREG, EDN1, and COL4A1, in three databases that may affect the progression of aSAH. The results of functional annotation revealed mechanisms mainly related to inflammation, smooth muscle cell proliferation and cell adhesion, potentially contributing to the occurrence of aSAH.
We demonstrate that specific miRNAs in plasma, including miR-23b-3p, miR-590-5p, miR-20b-5p, miR-142-3p, and miR-29b-3p, are significantly down-regulated in aSAH patients and may play a modulating role in its progression.
Objective: We aimed to investigate whether the efficacy and safety of clopidogrel plus aspirin vs aspirin alone were consistent between patients with and without intracranial arterial stenosis ...(ICAS), in the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. Methods: We assessed the interaction of the treatment effects of the 2 antiplatelet therapies among patients with and without ICAS, identified by magnetic resonance angiography (MRA) in CHANCE (ClinicalTrials.gov identifierNCT00979589). Results: Overall, 1,089 patients with MRA images available in CHANCE were included in this subanalysis, 608 patients (55.8%) with ICAS and 481 (44.2%) without. Patients with ICAS had higher rates of recurrent stroke (12.5% vs 5.4%; p < 0.0001) at 90 days than those without. But there was no statistically significant treatment by presence of ICAS interaction on either the primary outcome of any stroke (hazard ratio for clopidogrel plus aspirin vs aspirin alone: 0.79 0.47-1.32 vs 1.12 0.56-2.25; interaction p = 0.522) or the safety outcome of any bleeding event (interaction p = 0.277). Conclusions: The results indicated higher rate of recurrent stroke in minor stroke or high-risk TIA patients with ICAS than in those without. However, there was no significant difference in the response to the 2 antiplatelet therapies between patients with and without ICAS in the CHANCE trial.
Dissolved oxygen (DO) is an key factor for lipopeptide fermentation. To better understand the link between oxygen supply and lipopeptide productivity in Bacillus velezensis CMT-6, the mechanism of DO ...on the synthesis of antimicrobial lipopeptides by Bacillus velezensis CMT-6 was examined. The production of surfactin and iturin of CMT-6 was detected by liquid chromatography–mass spectrometer (LC-MS) under different DO conditions and transcriptome analysis was performed. At 100 and 200 rpm, the lipopeptides productions were 2753.62 mg/L and 3452.90 mg/L, respectively. There was no significant change in the yield of iturin but that of surfactin increased by 64.14%. Transcriptome analysis revealed that the enriched differential genes were concentrated in the GO term of oxidation–reduction process. The marked enrichment of the lipopeptides synthesis pathway, including microbial metabolism in diverse environments and carbon metabolism in the two-component system, were observed. More importantly, the expression levels of the four surfactin synthetase genes increased at higher DO, however, the iturin synthetase gene expression did not. Furthermore, modular surfactin synthetase was overexpressed (between 9- and 49-fold) at 200 rpm but not at 100 rpm, which is suggestive of efficient surfactin assembly resulting in surfactin overproduction. This study provides a theoretical basis for constructing engineering strains with high lipopeptide production to adapt to different DO.
The fractional pressure ratio is introduced to quantitatively assess the hemodynamic significance of severe intracranial stenosis. A computational fluid dynamics-based method is proposed to ...non-invasively compute the FPRCFD and compared against fractional pressure ratio measured by an invasive technique. Eleven patients with severe intracranial stenosis considered for endovascular intervention were recruited and an invasive procedure was performed to measure the distal and the aortic pressure (Pd and Pa). The fractional pressure ratio was calculated as
P
d
/
P
a
. The computed tomography angiography was used to reconstruct three-dimensional (3D) arteries for each patient. Cerebral hemodynamics was then computed for the arteries using a mathematical model governed by Navier–Stokes equations and with the outflow conditions imposed by a model of distal resistance and compliance. The non-invasive
P
d
-
CFD
,
P
a
-
CFD
, and FPRCFD were then obtained from the computational fluid dynamics calculation using a 16-core parallel computer. The invasive and non-invasive parameters were tested by statistical analysis. For this group of patients, the computational fluid dynamics method achieved comparable results with the invasive measurements. The fractional pressure ratio and FPRCFD are very close and highly correlated, but not linearly proportional, with the percentage of stenosis. The proposed computational fluid dynamics method can potentially be useful in assessing the functional alteration of cerebral stenosis.
Only a very few studies had compared the differences in topographic patterns of cerebral infarcts between middle cerebral artery (MCA) and internal carotid artery (ICA) disease. Besides, the ...comparison of clinical features and outcomes between MCA and ICA disease had rarely been reported.
To compare the clinical, imaging features and outcome of MCA versus ICA disease.
We prospectively enrolled 1172 patients with noncardiogenic ischemic stroke in ipsilateral ICA or MCA territory. Clinical, neuroradiologic and outcome of the two groups were compared in this observational cohort study.
The ICA group more frequently presented with decreased alertness, gaze palsy, aphasia, and neglect than the MCA group at admission, and more often had higher National Institute of Health stroke scale score at admission and discharge. Meanwhile, the ICA group more frequently had multiple acute infarcts, watershed infarcts, territorial infarct, small cortical infarct, and responsible artery stenosis ≥70%. Whereas penetrating artery infarct and parent artery occluding penetrating artery was more often associated with MCA disease. The ICA group more frequently had inhospital complications of pneumonia and deep vein thrombosis, more often had disability at discharge, and had more recurrent ischemic stroke or transient ischemic attack in 1 Year. Multivariable logistic regression identified male (OR, 1.99; 95% CI, 1.30 to 3.05; P = 0.002), history of coronary heart disease (OR, 1.85; 95% CI, 1.03 to 3.32; P = 0.041), multiple acute infarcts (OR, 4.18; 95% CI, 2.07 to 8.45; P<0.0001), and territorial infarct (OR, 2.23; 95% CI, 1.52 to 3.27; P<0.0001) was more often associated with ICA territory disease.
The clinical, radiologic characteristics and outcome are distinctively different between ICA and MCA disease. Compared to MCA disease, ICA disease has more serious clinical and radiologic manifestation, and poorer outcome.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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