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.

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.

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.

The "Double-Peak" Pattern of Pituitary Adenoma Intrasellar Pressure and Its Effects on the Microvascular Structure.

OBJECTIVE: The purpose of the present study was to investigate the relationship between the intrasellar pressure (ISP) and the microvascular structure of pituitary adenomas. METHODS: We retrospectively analyzed the ISP in 66 patients with pituitary adenomas. The corresponding microvascular structure was obtained using immunohistochemistry and analyzed for its correlation with the ISP. RESULTS: The average ISP was 25.89 ± 8.27 mm Hg, and the ISP was not related to the size of the adenoma (Pearson correlation coefficient, 0.103; P = 0.415). The ISPs of adenomas with different Knosp grades were significantly different (P < 0.05). From grade 0 to grade 4, at first, the ISP increased with the Knosp grade and reached the first peak at grade 2. It then decreased at grade 3 and increased again at grade 4, showing a "double-peak" pattern. The minimal diameter and perimeter of the microvessels and the vessel-covered area percentage were positively related to the ISP. When these parameters were compared among the adenomas of different Knosp grades, they also exhibited a "double-peak" pattern. CONCLUSIONS: In the present study, we found that with the increase in pituitary adenoma size and invasion of the surrounding tissues, the ISP of pituitary adenomas showed a "double-peak" pattern. The ISP and certain parameters of the microvascular structure are related, because the microvasculature adaptively changes its structure in response to the changing ISP to ensure a sufficient blood supply to the adenoma. The specific mechanism of this phenomenon requires further study.

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.

Falcine Sinus and Parafalcine Collateral Veins in Meningiomas Invading the Superior Sagittal Sinus.

BACKGROUND: Venous collaterals form because of occlusion of the superior sagittal sinus (SSS), thus preserving venous drainage. Previous studies have focused on the evaluation and protection of sinuses and cortical veins and have neglected the collaterals between the SSS and deep venous system, which are important for surgical planning. We aimed to study the venous compensatory patterns inside and on both sides of the cerebral falx (parafalx) in patients with meningioma invading the SSS. METHODS: Conventional magnetic resonance imaging, magnetic resonance venography, and a three-dimensional reconstructed venous model of 45 patients were analyzed. The venous collateral pattern of the parafalx was divided into 4 types: A), with cerebral medial cortical vein displacement or hyperplasia; B), collaterals connect the 2 ends of the occluded segment of the SSS; C), collaterals connect the occluded segment of the SSS with the deep cerebral venous system; and D), recanalization or secondary formation of a falcine sinus. The incidence of each type in different occlusion grades and positions of the SSS was analyzed. RESULTS: The 4 types of venous collaterals were ranked according to their prevalence: A, 46.7%; C, 15.6%; D, 8.9%; and B, 4.4%. The collaterals of types B, C, and D were found only in patients with severe SSS occlusion, and both types C and D were found only in middle and posterior occlusions of the SSS. CONCLUSIONS: In meningiomas invading the SSS, especially with complete posterior SSS occlusion, the parafalcine collateral veins and falcine sinus should be evaluated preoperatively to avoid iatrogenic injury.

Poor Brain-Tumor Interface-Related Edema Generation and Cerebral Venous Decompensation in Parasagittal Meningiomas.

BACKGROUND: Parasagittal meningioma (PSM) has a high incidence of peritumoral edema and unclear pathogenesis. The venous compression theory has been proposed as a pathomechanism; however, this is controversial, and the various edema patterns have not been recognized. OBJECTIVE: We sought to establish the relationship between venous circulation status with different edema patterns in PSM and the neurologic outcomes of these different patterns. METHODS: We performed a retrospective study of 60 consecutive patients who underwent surgical treatment for PSM. Patients were divided into 3 groups: no edema, poor brain-tumor interface-related edema (PIRE), and strong brain-tumor interface-related edema (SIRE). Single-blinded observers scored venous circulation for each patient based on the degree of superior sagittal sinus (SSS) occlusion, the number of involved cortical veins, and venous collateral grade. PIRE and SIRE were analyzed using multivariate analysis. Finally, we evaluated the functional independence and mobility score for every patient. RESULTS: The PIRE group showed the highest rate of cerebral venous decompensation at 75% (n = 15) compared with 38.5% (n = 5) in the SIRE group and 22.2% (n = 6) in the no-edema group. We observed a significant correlation between venous decompensation and PIRE generation on multivariate analysis (P = 0.029). The PIRE group showed the worst immediate functional status, and the SIRE group had the best improvement in complete dependence rate (23%) at late evaluation. CONCLUSIONS: The generation of PIRE, but not SIRE, may depend on venous decompensation in PSM. PIRE generation is predictive of worse neurologic outcome. Future studies into the pathogenesis of peritumoral edema should distinguish the different edema patterns.

miR-130b regulates the proliferation, invasion and apoptosis of glioma cells via targeting of CYLD.

MicroRNAs are short non-coding RNAs that play important roles in gliomas. However, the role of miR-130b in glioma remains unclear. In the present study, miR-130b expression was upregulated in glioma tissues and cell lines. Kaplan-Meier analysis indicated that the upregulation of miR-130b expression correlated with poor prognoses in glioma patients. Multivariate analysis demonstrated that this upregulation and a high-grade classification were independent factors that both predicted poor outcomes for glioma patients. Dual-luciferase assays identified that the cylindromatosis (CYLD) gene is a direct target of miR-130b. Functional studies demonstrated that a miR-130b mimic significantly promoted the growth and invasion of glioma cells, while also inhibiting apoptosis via selective targeting of CYLD, which was enhanced by CYLD-targeted siRNA. In contrast, a miR­130b inhibitor suppressed these biological behaviors, and this inhibition was reversed by CYLD-targeted siRNA. These data revealed that miR-130b could act as a novel potential diagnostic biomarker for glioma, while also demonstrating the importance of miR­130b in the cell proliferation and progression of glioma, indicating that it may serve as a useful therapeutic target for glioma.

Assessment and Treatment of Peritumoral Cortical Veins in Parasagittal Meningiomas with Application of 3-Dimensional Imaging Fusion Model.

BACKGROUND: Operation of cortical veins is the keystone of parasagittal meningioma (PSM) resection. Little is known about pathologic changes of the veins and proper treatment. We built 3-dimensional (3D) image fusion models by neuronavigation to analyze the features of peritumoral cortical veins for PSMs and explore intraoperative treatment options. METHODS: We performed a prospective study of 42 consecutive surgically treated PSM patients who underwent preoperative evaluation of peritumoral cortical veins using a 3D venous-tumor fusion model established by a neuronavigation system. We categorized cortical veins into 3 types: single-end anastomosis (type a), tumor-to-end anastomosis (type b), and end-to-end anastomosis (type c). We present surgical strategies to operate these veins. RESULTS: Preoperative evaluation demonstrated 39 patients with peritumoral cortical veins. The 3D models show 100% of the veins (95 in total), which were confirmed intraoperation. The postoperative complication rates after vein injury were 60% (type a), 16.7% (type c), and 0% (type b). Ten patients (23.8%) had residual tumor because of venous protection (equal to Simpson grade III). After correlation analysis, type b and c cortical veins were positively correlated with tumor volume. CONCLUSIONS: The anastomoses of cortical veins may provide compensation for venous transaction. There may be a time-evolution relationship between different cortical veins (type a to c to b). Treatment of cortical veins should follow the following principles: single-end veins must be protected, tumor-to-end veins should be transacted directly, and end-to-end veins could be cut selectivity based on the degree of occlusion of the superior sagittal sinus. Detailed preoperative assessment of peritumoral cortical veins is critical for proper treatment.