Artery Occlusion Research Articles

Cerebral Complications Following Facial Autologous Fat Graft Injection: A Systematic Review and Meta-analysis.

With the increasing use of autologous fat (AF) grafting in plastic surgery, the occurrence of complications has garnered the attention from plastic surgeons. This study aims to estimate the cerebral complications following facial AF graft injection objectively and systematically with newly published literature. A comprehensive literature search was conducted systematically on PubMed, Embase, Web of Science, Cochrane, and ClinicalTrials.gov for articles published between 2000 and 2023. A systematic review and meta-analysis were performed in accordance with PRISMA guidelines. A total of 11 articles comprising of 37 participants were included, all of which are case reports. For AF facial filling, the incidence rate of cerebral embolism among cases of cerebral and ocular embolism was found to be 60% (95% CI 0.41-0.79). The incidence of cerebral embolism presenting with initial symptoms of unconsciousness was 69% (95% CI 0.48-0.9), with limb movement disorders was 55% (95% CI 0.26-0.84), and with vision loss was 30% (95% CI 0.12-0.49). The incidence of cerebral embolism with ophthalmic artery occlusion was 36% (95% CI 0.20-0.53), compared to was 71% (95% CI 0.48-0.95) without ophthalmic artery occlusion. AF grafting is generally safe and minimally invasive. However, with its widespread use as facial injection filling for cosmetic enhancement, the incidence of cerebral complications, such as cerebral infarction, has also increased. It is imperative to properly manage high-risk factors for cerebral embolism during the perioperative period to prevent its occurrence. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Plasma Proteomics to Identify Drug Targets and Potential Drugs for Retinal Artery Occlusion: An Integrated Analysis in the UK Biobank.

Retinal artery occlusion (RAO), which is positively correlated with acute ischemic stroke (IS) and results in severe visual impairment, lacks effective intervention drugs. This study aims to perform integrated analysis using UK Biobank plasma proteome data of RAO and IS to identify potential targets and preventive drugs. A total of 7191 participants (22 RAO patients, 1457 IS patients, 8 individuals with both RAO and IS, and 5704 healthy age-gender-matched controls) were included in this study. Unique 1461 protein expression profiles of RAO, IS, and the combined data set, extracted from UK Biobank Plasma proteomics projects, were analyzed using both differential expression analysis and elastic network regression (Enet) methods to identify shared key proteins. Subsequent analyses, including single cell type expression assessment, pathway enrichment, and druggability analysis, were conducted for verifying shared key proteins and discovery of new drugs. Five proteins were found to be shared among the samples, with all of them showing upregulation. Notably, adhesion G-protein coupled receptor G1 (ADGRG1) exhibited high expression in glial cells of the brain and eye tissues. Gene set enrichment analysis revealed pathways associated with lipid metabolism and vascular regulation and inflammation. Druggability analysis unveiled 15 drug candidates targeting ADGRG1, which demonstrated protective effects against RAO, especially troglitazone (-8.5 kcal/mol). Our study identified novel risk proteins and therapeutic drugs associated with the rare disease RAO, providing valuable insights into potential intervention strategies.

Mitochondria-containing extracellular vesicles from mouse vs. human brain endothelial cells for ischemic stroke therapy

Ischemic stroke-induced mitochondrial dysfunction in the blood-brain barrier-forming brain endothelial cells (BECs) results in long-term neurological dysfunction post-stroke. We previously reported data from a pilot study where intravenous administration of human BEC (hBEC)-derived mitochondria-containing extracellular vesicles (EVs) showed a potential efficacy signal in a mouse middle cerebral artery occlusion (MCAo) model of stroke. We hypothesized that EVs harvested from donor species homologous to the recipient species (e.g., mouse) may improve therapeutic efficacy, and therefore, use of mouse BEC (mBEC)-derived EVs may improve post-stroke outcomes in MCAo mice.We investigated potential differences in the mitochondria transfer of EVs derived from the same species as the recipient cell (mBEC-EVs and recipient mBECs or hBECs-EVs and recipient hBECs) vs. cross-species EVs and recipient cells (mBEC-EVs and recipient hBECs or vice versa). Our results showed that while both hBEC- and mBEC-EVs transferred EV mitochondria, mBEC-EVs outperformed hBEC-EVs in increasing ATP levels and improved recipient mBEC mitochondrial function via increasing oxygen consumption rates. mBEC-EVs significantly reduced brain infarct volume and neurological deficit scores compared to vehicle-injected MCAo mice. The superior therapeutic efficacy of mBEC-EVs in MCAo mice support the continued use of mBEC-EVs to optimize the therapeutic potential of mitochondria-containing EVs in preclinical mouse models.

Microglial heterogeneity in the ischemic stroke mouse brain of both sexes

BackgroundIschemic stroke elicits a complex and sustained immune response in the brain. Immunomodulatory treatments have long held promise for improving stroke outcomes, yet none have succeeded in the clinical setting. This lack of success is largely due to our incomplete understanding of how immune cells respond to stroke. The objective of the current study was to dissect the effect of permanent stroke on microglia, the resident immune cells within the brain parenchyma.MethodsA permanent middle cerebral artery occlusion (pMCAO) model was used to induce ischemic stroke in young male and female mice. Microglia were sorted from fluorescence reporter mice after pMCAO or sham surgery and then subjected to single-cell RNA sequencing analysis. Various methods, including flow cytometry, RNA in situ hybridization, immunohistochemistry, whole-brain imaging, and bone marrow transplantation, were also employed to dissect the microglial response to stroke. Stroke outcomes were evaluated by infarct size and behavioral tests.ResultsFirst, we showed the morphologic and spatial changes in microglia after stroke. We then performed single-cell RNA sequencing analysis on microglia isolated from sham and stroke mice of both sexes. The data indicate no major sexual dimorphism in the microglial response to permanent stroke. Notably, we identified seven potential stroke-associated microglial clusters, including four major clusters characterized by a disease-associated microglia-like signature, a highly proliferative state, a macrophage-like profile, and an interferon (IFN) response signature, respectively. Importantly, we provided evidence that the macrophage-like cluster may represent the long-sought stroke-induced microglia subpopulation with increased CD45 expression. Lastly, given that the IFN-responsive subset constitutes the most prominent microglial population in the stroke brain, we used fludarabine to pharmacologically target STAT1 signaling and found that fludarabine treatment improved long-term stroke outcome.ConclusionsOur findings shed new light on microglia heterogeneity in stroke pathology and underscore the potential of targeting specific microglial populations for effective stroke therapies.

Chronic Thromboembolic Pulmonary Hypertension

Abstract: While the majority of patients have complete resolution of their acute pulmonary embolism (PE) after an adequate course of anticoagulation, some patients remain symptomatic with evidence of chronic PE. Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Chronic Thromboembolic Pulmonary Disease (CTEPD) are terms that describe symptomatic patients with chronic thromboembolic occlusions of the pulmonary arteries with or without pulmonary hypertension, respectively. Here, we review the definitions, epidemiology, pathobiology, diagnosis and management of CTEPH. The chronic PE in CTEPH is essentially a scar in the pulmonary vasculature and is accompanied by a pulmonary arteriolar vasculopathy. Ventilation-perfusion scanning is the most sensitive screening test for CTEPH, and diagnosis must be confirmed by right heart catheterization (RHC). Treatment decisions require a multidisciplinary team and guidance from additional imaging, usually CT or pulmonary angiography. While pulmonary endarterectomy (PEA) to remove the chronic PE surgically is still the first-line treatment for appropriate candidates, there is an expanding role for balloon pulmonary angioplasty (BPA) and medical treatment, as well as multimodality treatment approaches that incorporate all of those options. New imaging modalities and treatment strategies hold the promise to improve our care and management of CTEPH patients in the future.

Distal Transradial Access For Cardiac Catheterization in Patients Undergoing Hemodialysis.

Although a distal radial artery (DRA) approach has recently been used in patients undergoing cardiac catheterization, no studies have so far investigated the safety and feasibility of DRA in patients undergoing hemodialysis (HD). We aimed to investigate the incidence of conventional radial artery (CRA) occlusion and puncture site complications after DRA puncture in patients undergoing HD. We retrospectively analyzed the data of 117 consecutive patients with HD who underwent coronary angiography or percutaneous coronary intervention via a DRA approach at our institution from September 2017 to December 2019. The primary endpoint was the incidence of CRA occlusion after DRA puncture, as assessed via vascular ultrasonography. Secondary endpoints included difficulty achieving hemostasis, DRA occlusion, aneurysm, arteriovenous shunt, and acute ischemia. The DRA puncture was successful in 106 patients (success rate: 90.5%). Because 21 patients lacked postprocedural vascular ultrasonography data, the primary endpoint was evaluated in 85 patients. CRA occlusion occurred in three patients (3.5%) following DRA puncture. DRA occlusion and aneurysm occurred in five patients (5.9%) and one patient (1.2%), respectively. Catheterization through DRA is feasible in patients undergoing HD, with a clinically acceptable incidence of CRA and complications.

Safety and Efficacy of Injection Tenecteplase in 4.5 to 24 Hours Imaging Eligible Window Patients with Acute Ischemic Stroke (EAST-AIS) - Study Protocol

Abstract Background and Aims: Tenecteplase is used as the standard of care treatment for thrombolysis in acute ischemic stroke (AIS) patients within 4.5 h of symptom onset. Documented reports were less certain to claim the benefits of it in an extended window period. EAST-AIS (CTRI/2022/03/040718) trial is designed to determine the success rate of thrombolysis in an extended window period for good clinical outcomes. Study Design: It is a randomized, placebo-controlled trial of tenecteplase administered within 4.5–24 h of stroke onset (with or without large vessel occlusion) based on evidence of salvageable tissue through baseline computed tomography perfusion (CTP) or magnetic resonance imaging (MRI) scan. Criteria of patient inclusion are as follows: patients of both genders (male and female), age >18 years, pre-stroke modified Ranking Scale (mRS) <2, baseline NIHSS >5, CTP showing penumbra–ischemic core ratio >1.8, absolute difference in volume >10 ml, and ischemic core volume <70 ml. The sample size for the study is 100 patients: 50 in the tenecteplase arm (0.25 mg/kg body weight; maximum- 25 mg) and 50 in the placebo arm (controls). Study Outcomes: The study’s primary objective is safety endpoints along with the efficacy of tenecteplase assessed using the mRS score at 90 days of stroke onset. Conclusion: The result obtained from EAST-AIS will determine the safety and efficacy of tenecteplase injection administered 4.5–24 h following the symptom onset for AIS patients within the territory of Internal Carotid Artery (ICA), Middle Cerebral Artery (MCA), or Anterior Cerebral Artery (ACA) occlusion.

Comparative effectiveness of antiplatelet therapies for saphenous venous graft occlusion and cardiovascular outcomes: a network meta-analysis.

The ideal antiplatelet therapy to maintain graft patency after coronary artery bypass graft surgery (CABG) remains controversial. This review of randomized controlled trials (RCTs) aims to compare aspirin monotherapy, ticagrelor monotherapy, dual antiplatelet therapy (DAPT) with aspirin and ticagrelor (Asp+Tica) or with aspirin and clopidogrel (Asp+Clopi) to evaluate differences in post-CABG saphenous vein graft (SVG) occlusion, internal mammary artery (IMA) occlusion, myocardial infarction (MI), bleeding, and all-cause mortality (ACM) rates. The literature review was conducted on several electronic databases, including Medline, Embase, and Cochrane Central, from inception to August 10, 2022. Data was extracted using a predefined proforma. A Bayesian random-effects model was used for calculating point effect estimates (odds ratio and standard deviation). Quality assessment was done using the Cochrane RoB-2 tool. Ten RCTs comprising 2139 patients taking anti-platelets post-CABG were included. For preventing SVG occlusion, Asp+Tica showed the lowest mean AR of 0.144±0.068. Asp+Tica also showed a trend toward lesser postoperative MI risk and lower ACM rates, with a mean AR of 0.040±0.053 and 0.018±0.029, respectively. For maintaining IMA graft patency, Asp+Clopi showed the lowest mean AR of 0.092±0.053. Ticagrelor had the lowest mean AR of 0.049±0.075, with Asp+Tica showing a similar mean AR of 0.049±0.045 for postoperative major bleeding risk. Our analysis demonstrates that Asp+Tica can be the ideal therapy for patients undergoing CABG using SVG as it decreases the risk of post-CABG SVG occlusion and is not associated with a significantly higher risk for major bleeding.

Discovering Novel Plasma Biomarkers for Ischemic Stroke: Lipidomic and Metabolomic Analyses in an Aged Mouse Model

Ischemic stroke remains a leading cause of mortality and long-term disability worldwide, necessitating efforts to identify biomarkers for diagnosis, prognosis, and treatment monitoring. The present study aimed to identify novel plasma biomarkers of neurodegeneration and inflammation in a mouse model of stroke induced by distal middle cerebral artery (MCA) occlusion. Using targeted lipidomic and global untargeted metabolomic profiling of plasma collected from aged male mice 24 hours after stroke and weekly thereafter for 7 weeks, we discovered distinct acute and chronic signatures. In the acute phase, we observed elevations in myelin-associated lipids, including sphingomyelin (SM) and hexosylceramide (HCER) lipid species, indicating brain lipid catabolism. In the chronic phase, we identified 12-hydroxyeicosatetraenoic acid (12-HETE) as a putative biomarker of prolonged inflammation, consistent with our previous observation of a biphasic pro-inflammatory response to ischemia in the mouse brain. These results provide insight into the metabolic alterations detectable in the plasma after stroke and highlight the potential of myelin degradation products and arachidonic acid derivatives as biomarkers of neurodegeneration and inflammation, respectively. These discoveries lay the groundwork for further validation in human studies and may improve stroke management strategies.

Hypomethylated leptin receptor reduces cerebral ischaemia-reperfusion injury by activating the JAK2/STAT3 signalling pathway.

To investigate the cerebroprotective effects of leptin in vitro and in vivo via the Janus kinase-2 (JAK2)/transcription factor signal transducer and activators of transcription-3 (STAT3) pathway and leptin receptors (LEPR). The study used the cellular oxygen-glucose deprivation (OGD) model in PC12 cells and the middle cerebral artery occlusion (MCAO) rat model of cerebral ischaemia-reperfusion injury (CIRI) to assess changes in gene expression and protein levels following leptin pretreatment. The methylated DNA immunoprecipitation (MeDIP) assay measured DNA methylation levels. The optimal leptin concentration for exerting neuroprotective effects against ischaemia-reperfusion injury in PC12 cells was 200 ng/ml in vitro, but excessive leptin diminished this effect. Leptin pretreatment in the MCAO rat model demonstrated a similar effect to previously reported leptin administration post-CIRI. In addition to regulating the expression of inflammation-related cytokines, Western blot analysis showed that leptin pretreatment upregulated BCL-2 and downregulated caspase 3 levels. The MeDIP analysis demonstrated that DNA methylation regulated LEPR gene expression in the MCAO rat model when leptin pretreatment was used. Exogenous leptin might bind to extra-activated LEPR by reducing the methylation level of the LEPR gene promoter region, which leads to an increase in phosphorylated JAK2/STAT3 and apoptotic signalling pathways.

AD16 attenuates neuroinflammation induced by cerebral ischemia through down-regulating astrocytes A1 polarization

A1 polarization of astrocytes mediated prolonged inflammation contributing to brain injury in ischemic stroke. We have previously shown that AD16 protects against neonatal hypoxic-ischemic brain damage in vivo and oxygen-glucose deprivation in vitro. More recently, AD16 has demonstrated safety, tolerability, and favorable pharmacokinetics in a randomized controlled phase I trial. In this study, we utilized a rat model of transient middle cerebral artery occlusion (tMCAO) to explore whether the anti-inflammatory compound AD16 protects against ischemic brain injury by regulating A1 polarization and its underlying mechanisms. Our results showed that AD16 treatment significantly reduced the brain infarcted volume and improved neurological function in tMCAO rats. GO analysis results show that differential genes among the Sham, tMCAO and AD16 treatment groups are involved in the regulation of cytokine and inflammatory response. KEGG enrichment pathways analysis mainly enriched in cytokine-cytokine receptor interaction, viral protein interaction with cytokine-cytokine receptor, TNF, chemokine, NF-κB and IL-17 signaling pathway. Furthermore, AD16 treatment decreased the permeability of the blood-brain barrier and suppressed neuroinflammation. AD16 treatment also significantly reduced the polarization of A1 and inhibited NF-κB and JAK2/STAT3 signaling pathways. This study demonstrates that AD16 protects against brain injury in ischemic stroke by reducing A1 polarization to suppress neuroinflammation through downregulating NF-κB and JAK2/STAT3 signaling. Our findings uncover a potential molecular mechanism for AD16 and suggest that AD16 holds promising therapeutic potential against cerebral ischemia.

Electroacupuncture ameliorates blood-brain barrier disruption after ischemic stroke through histone acetylation regulation at the matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 2 genes.

To explore whether the regulation of matrix metalloproteinase 9 (MMP-9)/ tissue inhibitors of MMPs (TIMPs) gene expression through histone acetylation is a possible mechanism by which electroacupuncture (EA) protects blood-brain barrier (BBB) integrity in a middle cerebral artery occlusion (MCAO) rat model. Male Sprague-Dawley rats were divided into four groups: the sham group, the MCAO group, the MCAO + EA (MEA) group, and the MCAO + EA + HAT inhibitor (HATi) group. The MCAO model was generated by blocking the middle cerebral artery. EA was applied to Baihui (GV20). Samples were collected 1 or 3 d after reperfusion. Neurological function scores and Evans blue extravasation were employed to evaluate the poststroke injury. The effect of EA on MMP-9/TIMPs gene expression was assessed by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and chromatin immunoprecipitation (ChIP). Our results showed that EA treatment prominently improved neurological function and ameliorated BBB disruption. The RT-qPCR assay showed that EA reduced the expression of MMP-9 and promoted TIMP-2 mRNA expression, but HATi reversed these effects of EA. In addition, ChIP results revealed that EA decreased the enrichment of H3K9ace/H3K27ace at MMP-9 promoters and notably stimulated the recruitment of H3K9ace/H3K27ace at TIMP-2 promoter. EA treatment at Baihui (GV20) regulates the transcription of MMP-9 and TIMP-2 through histone acetylation modification in the acute stage of stroke, which preserves the structural integrity of the BBB in MCAO rats. These findings suggested that the histone acetylation-mediated transcriptional activity of target genes may be a crucial mechanism of EA treatment in stroke.

Caffeine Abstinence in Habituated Users: Cardiovascular Responses to Exercise With Blood Flow Restriction.

Blood flow restriction resistance exercise studies often require caffeine abstinence to avoid cardiovascular effects that could change the blood flow restriction stimulus. However, effects may be attenuated for habituated users. To compare cardiovascular responses to blood flow restriction resistance exercise when habituated users consume or abstain from caffeine. Thirty participants completed a 3-visit within-subject study beginning with familiarization and caffeine intake questionnaire. Visits 2 and 3 consisted of blood flow restriction resistance exercise (3 sets bicep curls to failure, 30% 1-repetition max, 40% arterial occlusion pressure [AOP]), following participants' normal caffeine consumption (CAFF) or abstaining (ABS). AOP, systolic (SBP) and diastolic (DBP) blood pressure, and heart rate were measured preexercise and postexercise. Prevalues and preexercise to postexercise change scores for SBP, DBP, AOP (all millimeters of mercury), heart rate (in beats per minute), and repetitions were compared between conditions. Results are represented as mean (SD). Preexercise AOP was similar for CAFF (137.8 [14.4]) and ABS (137.1 [14.9], BF10 = 0.2), although pre-SBP was higher for CAFF (115.4 [9.8]) than ABS (112.3 [9.4], BF10 = 1.9). Pre-DBP was similar between conditions. The exercise-induced change in AOP was greater for CAFF (18.4 [11.2]) than ABS (13.2 [14.9]), though evidence was anecdotal (BF10 = 0.7). Exercise-induced changes in SBP, DBP, and heart rate were similar between conditions (all BF10 ≤ 0.40). More repetitions were completed for CAFF (63 [26]) than ABS (57 [17], BF10 = 2.1). The findings of this study suggest that for habituated users, maintaining daily caffeine habits will not have substantial effects on common cardiovascular variables relevant to blood flow restriction.

Rationale and design of the artificial intelligence scalable solution for acute myocardial infarction (ASSIST) study

BackgroundAcute coronary syndrome (ACS), specifically ST-segment elevation myocardial infarction is a major cause of morbidity and mortality throughout Europe. Diagnosis in the acute setting is mainly based on clinical symptoms and physician's interpretation of an electrocardiogram (ECG), which may be subject to errors. ST-segment elevation is the leading criteria to activate urgent reperfusion therapy, but a clear ST-elevation pattern might not be present in patients with coronary occlusion and ST-segment elevation might be seen in patients with normal coronary arteries. MethodsThe ASSIST project is a retrospective observational study aiming to improve the ECG-assisted assessment of ACS patients in the acute setting by incorporating an artificial intelligence platform, Willem™ to analyze 12‑lead ECGs. Our aim is to improve diagnostic accuracy and reduce treatment delays. ECG and clinical data collected during this study will enable the optimization and validation of Willem™. A retrospective multicenter study will collect ECG, clinical, and coronary angiography data from 10,309 patients. The primary outcome is the performance of this tool in the correct identification of acute myocardial infarction with coronary artery occlusion. Model performance will be evaluated internally with patients recruited in this retrospective study while external validation will be performed in a second stage. ConclusionASSIST will provide key data to optimize Willem™ platform to detect myocardial infarction based on ECG-assessment alone. Our hypothesis is that such a diagnostic approach may reduce time delays, enhance diagnostic accuracy, and improve clinical outcomes.

Cataract Surgery and Incidence of Retinal Vascular Occlusion: Population-Based Cohort Study Using a Target Trial Emulation Framework

BackgroundPrevious studies suggested an association between cataract surgery and retinal vascular occlusion. However, the association may be attributable to detection bias because postoperative monitoring may be more frequent for those who receive cataract surgery than for those who do not. DesignPopulation-based cohort study using target trial emulation framework. MethodsWe included patients with cataract aged 50 years and older receiving cataract surgery or non-surgical interventions identified from the Taiwan National Health Insurance Research Database between 2003 and 2018, matched by propensity score. The primary outcome was retinal vascular occlusion. Cox proportional hazards models were used to compare surgery and control groups. Additional analyses were restricted to patients who had undergone fundoscopic examination within 6 months prior to cataract surgery to address the issue of detection bias. ResultsWe included 577,129 cataract surgery and control pairs. We found the hazard ratio (HR) for retinal vascular occlusion after cataract surgery was 1.23 (95% confidence interval (CI): 1.17-1.29), compared with the control group. Secondary outcome analyses yielded similar results for retinal artery occlusion (HR: 1.13, 95% CI: 1.02-1.26) and retinal vein occlusion (HR: 1.26, 95% CI: 1.20-1.33). However, no risk of retinal vascular occlusion was observed among patients who had received fundoscopic examinations (HR: 1.06, 95% CI: 0.98-1.15) at baseline. ConclusionsOur study underscored the importance of conducting complete baseline fundoscopic examinations before cataract surgery to clarify whether postoperative conditions are due to patients’ underlying diseases or unintended complications of cataract surgery.

Injectable, antioxidative, and loaded with exosomes/Liproxstatin-1 hydrogel as a potential treatment for retinal ischemia–reperfusion by inhibiting ferroptosis and apoptosis

Retinal ischemia–reperfusion is a major cause of vision loss in a variety of ocular diseases, including glaucoma, age-related macular degeneration, diabetic retinopathy, and central retinal artery occlusion. Previous studies have reported the protective effects of injectable hydrogels in optic nerve injury, but reports of multifunctional hydrogels loaded with drugs and bioactive substances that synergistically promote neuroprotection are rare. Here, we designed an injectable, drug-loaded, and reactive oxygen species responsive multifunctional hydrogel. Upon intravitreal injection into a retinal ischemia–reperfusion injury model in mice, the hydrogel released exosomes and liproxstatin-1 over an extended period exceeding a month, leading to a significant recovery of visual function and reduction of retinal ganglion cell loss. The effect was superior to that of the common drug and exosome combination. The results of this study suggest that this multifunctional hydrogel is expected to advance retinal tissue engineering and provide an innovative strategy for acute neuroprotection in retinal ischemia–reperfusion injury.

Hyperglycemia induces microglial pyroptosis by increasing oxygen extraction rate: Implication in neurological impairment during ischemic stroke.

Elevated levels of blood glucose in patients with ischemic stroke are associated with a worse prognosis. The present study aimed to explore whether hyperglycemia promotes microglial pyroptosis by increasing the oxygen extraction rate in an acute ischemic stroke model. C57BL/6 mice that underwent middle cerebral artery occlusion were used for assessment of blood glucose level and neurological function. The cerebral oxygen extraction ratio (CERO2), oxygen consumption rate (OCR) and partial pressure of brain tissue oxygen (PbtO2) were measured. To investigate the significance of the NOD‑like receptor protein 3 (NLRP3) inflammasome, NLRP3‑/‑ mice were used, and the expression levels of NLRP3, caspase‑1, full‑length gasdermin D (GSDMD‑FL), GSDMD‑N domain (GSDMD‑N), IL‑1β and IL‑18 were evaluated. In addition, Z‑YVAD‑FMK, a caspase‑1 inhibitor, was used to treat microglia to determine whether activation of the NLRP3 inflammasome was required for the enhancing effect of hyperglycemia on pyroptosis. It was revealed that hyperglycemia accelerated cerebral injury in the acute ischemic stroke model, as evidenced by decreased latency to fall and the percentage of foot fault. Hyperglycemia aggravated hypoxia by increasing the oxygen extraction rate, as evidenced by increased CERO2 and OCR, and decreased PbtO2 in response to high glucose treatment. Furthermore, hyperglycemia‑induced microglial pyroptosis was confirmed by detection of increased levels of caspase‑1, GSDMD‑N, IL‑1β and IL‑18 and a decreased level of GSDMD‑FL. However, the knockout of NLRP3 attenuated these effects. Pharmacological inhibition of caspase‑1 also reduced the expression levels of GSDMD‑N, IL‑1β and IL‑18 in microglial cells. These results suggested that hyperglycemia stimulated NLRP3 inflammasome activation by increasing the oxygen extraction rate, thus leading to the aggravation of pyroptosis following ischemic stroke.

Huanglian Jiedu decoction alleviates ischemia-induced cerebral injury in rats by mitigating NET formation and activiting GABAergic synapses.

Huanglian Jiedu decoction (HLJD) has been used to treat ischemic stroke in clinic. However, the detailed protective mechanisms of HLJD on ischemic stroke have yet to be elucidated. The aim of this study is to elucidate the underlying pharmacological mechanisms of HLJD based on the inhibition of neuroinflammation and the amelioration of nerve cell damage. A middle cerebral artery occlusion reperfusion (MCAO/R) model was established in rats and received HLJD treatment. Effects of HLJD on neurological function was assessed based on Bederson's score, postural reflex test and asymmetry score. 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining, Hematein and eosin (HE) and Nissl staining were used to observe the pathological changes in brain. Then, transcriptomics was used to screen the differential genes in brain tissue in MCAO/R model rats following HLJD intervention. Subsequently, the effects of HLJD on neutrophil extracellular trap (NET) formation-related neuroinflammation, gamma-aminobutyric acid (GABA)ergic synapse activation, nerve cell damage and proliferation were validated using immunofluorescence, western blot and enzyme-linked immunosorbent assay (ELISA). Our results showed that HLJD intervention reduced the Bederson's score, postural reflex test score and asymmetry score in MCAO/R model rats. Pathological staining indicated that HLJD treatment decreased the cerebral infarction area, mitigated neuronal damage and increased the numbers of Nissl bodies. Transcriptomics suggested that HLJD affected 435 genes in MCAO/R rats. Among them, several genes involving in NET formation and GABAergic synapses pathways were dysregulated. Subsequent experimental validation showed that HLJD reduced the MPO+CitH3+ positive expression area, reduced the protein expression of PAD4, p-P38/P38, p-ERK/ERK and decreased the levels of IL-1β, IL-6 and TNF-α, reversed the increase of Iba1+TLR4+, Iba1+p65+ and Iba1+NLRP3+ positive expression area in brain. Moreover, HLJD increased GABA levels, elevated the protein expression of GABRG1 and GAT3, decreased the TUNEL positive expression area and increased the Ki67 positive expression area in brain. HLJD intervention exerts a multifaceted positive impact on ischemia-induced cerebral injury in MCAO/R rats. This intervention effectively inhibits neuroinflammation by mitigating NET formation, and concurrently improves nerve cell damage and fosters nerve cell proliferation through activating GABAergic synapses.

Individuals Can be Taught to Sense the Degree of Vascular Occlusion: Implications for Practical Blood Flow Restriction.

Song, JS, Hammert, WB, Kataoka, R, Yamada, Y, Kang, A, and Loenneke, JP. Individuals can be taught to sense the degree of vascular occlusion: Implications for practical blood flow restriction. J Strength Cond Res 38(8): 1413-1418, 2024-It is currently unknown if individuals can be conditioned to a relative arterial occlusion pressure (AOP) and replicate that pressure at a later time point. The purpose of this study was to determine whether individuals can be taught to sense a certain relative pressure (i.e., target pressure) by comparing a conditioning method with a time-matched non-conditioning control. Fifty-eight subjects completed 2 visits in a randomized order: (a) conditioning condition and (b) time-matched control condition. The conditioning involved 11 series of inflations to 40% AOP for 12 seconds followed by cuff deflation for 22 seconds. The pressure estimations were taken at 5 and 30 minutes after each condition. Data are presented as mean differences (95% credible interval). The absolute error at 5 minutes was greater for the control compared with conditioning condition (7.1 [2.0-12.1] mm Hg). However, this difference in absolute error between conditioning and control was reduced at 30 minutes (2.9 [-1.3 to 7.1] mm Hg). The mean difference and 95% limits of agreement for the control were 8.2 (-42.4 to 58.5) mm Hg at 5 minutes and 0.02 (-43.5 to 43.5) at 30 minutes. The agreements for the conditioning were -6.2 (-32.4 to 20.0) mm Hg at 5 minutes and -11.2 (-36.6 to 14.3) mm Hg at 30 minutes. The results suggest that the individuals can be taught to sense the target pressure, but this effect only lasts a short amount of time. Future work is necessary to refine the conditioning method to extend the duration of this conditioning effect.

AMALRIC TRIANGULAR SIGN AND CAROTID DOPPLER ULTRASONOGRAPHIC FINDINGS IN CENTRAL RETINAL ARTERY OCCLUSION.

The aim of this study was to determine the incidence of the Amalric triangular sign (ATS) in patients with central retinal artery occlusion and investigate its association with visual function and carotid Doppler ultrasonography findings. A retrospective chart review was conducted on 21 eyes from 21 patients with complete central retinal artery occlusion. Best-corrected visual acuity and carotid Doppler ultrasonography findings [peak systolic velocity, end-diastolic velocity, and resistance index (RI) = (PSV - EDV)/PSV] were investigated. Three patients (14%) exhibited the ATS. Best-corrected visual acuity at first visit was significantly worse in ATS-positive patients than in ATS-negative patients (P = 0.024). Doppler waveform analysis of the common carotid artery showed that ATS-positive patients had a significantly lower end-diastolic velocity [P = 0.009, median 10 (range 9-10) vs. 17 (13-24) m/second] and significantly higher resistance index [P = 0.021, median 0.80 (range 0.79-0.83) vs. 0.72 (0.66-0.82)] than did ATS-negative. The Amalric triangular sign was observed in three patients with central retinal artery occlusion, who showed worse best-corrected visual acuity at the first visit than did those without the ATS. Carotid Doppler ultrasonography revealed that ATS-positive patients had a significantly higher resistance index and lower end-diastolic velocity at the common carotid artery than did ATS-negative, indicating steno-occlusive changes in the internal carotid artery.