Search Results (786)

Objective: Malignant middle cerebral artery infarction is associated with high mortality despite decompressive craniectomy. Reliable biomarkers predicting early outcome remain limited. The aim of this study was to evaluate the prognostic significance of inflammatory biomarkers, particularly the systemic immune–inflammation index (SII), for predicting in-hospital mortality in patients undergoing decompressive craniectomy for malignant middle cerebral artery infarction. Methods: This retrospective study included 31 patients who underwent decompressive craniectomy for malignant MCA infarction between 2014 and 2024. Demographic, clinical, radiological, and laboratory variables were analyzed. Results: Overall in-hospital mortality was 61.3%. Non-survivors had significantly higher SII, neutrophil count, neutrophil-to-lymphocyte ratio, serum creatinine, and higher prevalence of hypertension and anticoagulant therapy. ROC analysis showed that SII had the highest predictive performance (AUC = 0.833). Multivariate analysis identified age, serum creatinine, NLR, SII, hypertension, and anticoagulant therapy as independent predictors of mortality. Patients aged ≥65 years had significantly higher in-hospital mortality than younger patients. Conclusions: Elevated SII is a strong independent predictor of early mortality after decompressive craniectomy and may serve as a simple and clinically applicable biomarker for risk stratification. Full article

Background/Objectives: Ischemic stroke remains a major global health challenge, yet therapeutic options are severely restricted by narrow treatment windows and the risk of hemorrhagic transformation. Natural small molecules represent a valuable reservoir for discovering novel neuroprotective leads with favorable safety profiles. Cinchonidine, a natural quinoline alkaloid, has shown anti-inflammatory and cytoprotective properties, but its potential in treating ischemic stroke is largely unexplored. This study aimed to evaluate the neurovascular protective effects and hemostatic safety of cinchonidine in preclinical stroke models. Methods: We evaluated cinchonidine using a mouse model of middle cerebral artery occlusion (MCAO) and in vitro oxygen–glucose deprivation (OGD) models in cerebral endothelial cells (CECs) and Neuro2A cells. Infarct volume, brain edema, and neurological recovery were assessed. Blood–brain barrier (BBB) integrity was measured via Evans blue extravasation. Mechanistic markers, including microglial activation, pro-inflammatory mediators (iNOS, COX-2), and apoptosis-related signaling, were examined. Additionally, cinchonidine’s effect on platelet aggregation was also tested. Results: Cinchonidine significantly reduced infarct volume and brain edema while improving neurological functional recovery. It effectively preserved BBB integrity and enhanced cell viability under OGD conditions. Furthermore, cinchonidine suppressed microglial activation and decreased the expression of pro-inflammatory mediators. These protective effects were associated with the modulation of apoptotic signaling pathways. These protective effects were accompanied by reduced p53-associated stress signaling in endothelial cells and ischemic brain tissue. Importantly, cinchonidine did not significantly interfere with platelet aggregation, suggesting a potentially favorable hemostatic profile. Conclusions: Cinchonidine attenuates ischemic brain injury and is associated with endothelial protection, preservation of BBB integrity, and modulation of inflammatory and apoptotic responses. As a natural lead compound that does not compromise hemostasis, cinchonidine represents a promising lead compound for further development as a neurovascular protective strategy in ischemic stroke. Full article

Background: Scutellaria baicalensis (Scu) extract has been traditionally used in the treatment of stroke-related syndromes, yet its underlying molecular mechanisms, particularly those involving ferroptosis, remain to be fully elucidated. Purpose: This study aims to validate the hypothesis that Scu extract improves cerebral ischemia-reperfusion injury (CIRI) by inhibiting ferroptosis through the PI3K/AKT signaling pathway. Methods: This study employed middle cerebral artery occlusion (MCAO) in male Sprague-Dawley (SD) rats and oxygen–glucose deprivation/reoxygenation (OGD/R) models to evaluate the protective effects of Scu extract against CIRI. Multiple approaches were integrated to elucidate the underlying mechanisms. Furthermore, a range of experimental techniques, including neurological function assessment, TTC staining, histopathological analysis, biochemical assays, qPCR, transmission electron microscopy (TEM), reactive oxygen species (ROS) detection, Western blotting, and immunofluorescence, were used to comprehensively validate its neuroprotective effects. Results: Scu extract significantly improved neurological outcomes and attenuated brain injury in MCAO rats. Proteomic analysis revealed significant enrichment of ferroptosis-related pathways, which was supported by reduced mitochondrial damage, decreased iron accumulation, and restoration of the SLC7A11/GPX4 axis. Subsequently, UPLC/Q-TOF-MS analysis revealed that four major bioactive components were absorbed in MCAO rats. KEGG pathway analysis based on network pharmacology further indicated that the PI3K/AKT signaling pathway is a key regulatory target. Notably, pharmacological inhibition of PI3K with LY294002 markedly abolished the anti-ferroptotic effects of Scu extract, which was further confirmed in vitro. Conclusions: This study demonstrates that Scu extract confers neuroprotection against CIRI in MCAO rats potentially through inhibiting ferroptosis via activation of the PI3K/AKT pathway. Full article

Postoperative delirium (POD) is a common neurocognitive complication after cardiac surgery in elderly patients and is associated with adverse clinical outcomes. Impaired cerebral autoregulation and reduced cerebrovascular reserve may contribute to POD development. Automated transcranial Doppler sonography (TCD) enables non-invasive assessment of intracranial hemodynamics and may provide additional information for perioperative risk assessment. In this prospective single-center observational study, 108 patients aged >70 years scheduled for elective cardiac surgery with cardiopulmonary bypass were enrolled. Patients who had pre-existing neurological disease, had a pathological carotid Doppler ultrasound, underwent emergency surgery, or were unable to undergo delirium screening were excluded. Preoperative bilateral TCD of the middle cerebral arteries was performed using an automated WAKIe R3 system. POD was assessed on postoperative days 1–3 using the CAM-ICU. The primary endpoint was the occurrence of POD. Twenty-one patients were excluded, leaving 87 patients for analysis. POD occurred in 14 patients (16%). All patients who developed POD had pathological preoperative TCD findings, whereas no POD occurred among patients with normal TCD examinations. Overall, 82 patients (94%) demonstrated pathological intracranial hemodynamic findings despite normal carotid Doppler ultrasound. In multivariable Firth logistic regression adjusted for age and sex, pathological TCD findings remained associated with POD; however, interpretation was limited by the small number of outcome events and quasi-complete separation. In elderly patients undergoing cardiac surgery with cardiopulmonary bypass, pathological preoperative TCD findings were frequently observed and may be associated with an increased risk of postoperative delirium. The marked discrepancy between normal carotid ultrasound and abnormal intracranial hemodynamics suggests that TCD may provide complementary information regarding cerebrovascular function. Given the limited sample size and event rate, these findings should be considered exploratory and require confirmation in larger multicenter studies. Full article

Background/Objectives: Papua New Guinea has a population of over 10 million, with its public cardiac surgical service provided by only one tertiary center. Despite the climbing burden of ischemic heart disease, no CABG operation has been performed before 2025 due to limited local surgical capacity. An international collaboration was planned in order to launch a CABG program in the country. Methods: Three cases were shortlisted after a multidisciplinary team discussion. A team-based “On-the-job” mentoring strategy was employed to facilitate skill transfer. The operation was carried out in a “twinning” fashion, with each role of the surgical team being taken up by “a pair”—the trainer (visiting team) and the learner (local team). The trainer demonstrated key skills and tips in the first case, and the “pair” switched positions in the following cases to maximize hands-on learning. The last case was performed entirely by the local team. Results: Three patients underwent CABG operations in this pilot program. A total of 2.33 grafts/case were performed on average, with no 30-day mortality. There were no major complications except for one patient developing right middle cerebral artery infarct on postoperative day 5. The patient was discharged one month later after achieving functional recovery and was started on anticoagulation therapy. Conclusions: International collaborations with strategic planning can play a critical role in starting new cardiac surgical programs in low–middle-income countries, with acceptable surgical outcomes. History has been made with the first-ever CABG operation successfully performed in Papua New Guinea. The journey ahead to sustain local cardiac surgical capacity and to provide safe and accessible cardiac surgical care for the country remains challenging. Full article

Background: Ischemic stroke remains a leading cause of mortality and disability worldwide. Despite extensive preclinical research, most neuroprotective strategies have failed to translate into clinical benefit, partly due to methodological variability. The transient intraluminal filament middle cerebral artery occlusion (tifMCAO) model is widely used, yet its implementation lacks consistency. This review aimed to characterize tifMCAO methodologies in adult rats and examine how experimental variability relates to reported outcomes. Methods: A systematic review was conducted following PRISMA guidelines. Studies using tifMCAO in adult rats were included. MEDLINE (PubMed), Web of Science, and Scopus were searched up to March 2025. Risk of bias was assessed using the SYRCLE tool and reporting quality using the ARRIVE checklist. The protocol was registered in PROSPERO (CRD420251140869). Results were synthesized narratively. Results: A total of 125 studies were included. A commonly used framework involved male Sprague–Dawley rats (6–12 weeks), silicone-coated monofilaments, occlusion durations of 60–120 min (most frequently 90 min), and isoflurane anesthesia, although this reflects methodological convergence rather than true standardization. Substantial variability was observed across methodological parameters. Variations in ischemia duration, filament properties, and anesthesia were associated with differences in infarct size, blood–brain barrier disruption, and functional outcomes. Conclusions: The tifMCAO model shows partial methodological convergence alongside significant variability influencing outcomes. Improved standardization and reporting are essential to enhance reproducibility and translational relevance. Full article

Background/Objectives: Rheumatoid arthritis (RA) has been associated with accelerated atherosclerosis and cerebrovascular alterations. Our 2017 study compared 60 RA patients to healthy controls, assessing vascular, neurological, and cognitive parameters. The present study is a follow-up of these RA patients to evaluate disease progression and vascular changes over time, using their 2017 results as baseline. Methods: In 2023, we reassessed 43 of the original 60 RA patients using laboratory testing, carotid ultrasound, functional transcranial Doppler (TCD) and brain magnetic resonance imaging (MRI) examinations. Changes over time were analyzed within the same individuals. Results: Inflammatory markers and lipid profiles showed a trend toward improvement, though changes were not statistically significant, except for a significant increase in vitamin D (p < 0.001) and a decrease in Disease Activity Score in 28 Joints (DAS28) scores (p < 0.001). Carotid ultrasound revealed a significant increase in plaque burden (p = 0.022 on the right side and p = 0.008 on the left), while carotid intima media thickness (cIMT) showed a non-significant rise. TCD measurements indicated significantly increased pulsatility (p < 0.001 on the right, p = 0.001 on the left side) and resistance (p = 0.001 on the right, p = 0.012 on the left side) indices and reduced flow velocities (p < 0.001 on the right and p = 0.001 on the left side) in bilateral middle cerebral arteries (MCAs). The cerebrovascular reserve capacity was significantly lower on the right side overall (p = 0.013), with further decline noted in the methotrexate (MTX)-treated subgroup on the left side (p = 0.043). MRI findings showed non-significant numerical trends toward worsening lacunar small-vessel disease (p = 0.405) and cerebral atrophy (p = 0.063), with higher but stable lacunar infarction scores among MTX users (p = 0.023). Conclusions: Despite improved inflammatory control, RA patients demonstrated progressive vascular and hemodynamic alterations over time, while MRI changes should be interpreted as trends. These findings support multimodal vascular monitoring in RA. Full article

Background: Mitochondrial dysfunction is a central event in the pathogenesis of ischemic stroke. The roles of specific mitochondrial complex subunits, such as NDUFA4 and NDUFB3, in cerebral ischemia–reperfusion injury remain poorly defined. This study aims to investigate the dynamic expressions and functional impact of NDUFA4 and NDUFB3 in ischemic stroke. Methods: A transient middle cerebral artery occlusion (MCAO) model was established in male C57BL/6J mice. Label-free quantitative proteomics and Western blotting were employed to analyze protein expression in the ischemic penumbra. Highly differentiated PC12 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) or glutamate excitotoxicity to mimic ischemic injury in vitro. The functional consequences of NDUFB3 knockdown and overexpression were assessed by measuring ATP levels, reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), and apoptosis. The involvement of the JNK-mediated mitochondrial apoptotic pathway was also examined. Results: Proteomic analysis revealed a significant upregulation of NDUFA4 and NDUFB3 in the ischemic penumbra of MCAO mice, as verified by western blot. In highly differentiated PC12 cells, both OGD/R and glutamate exposure induced a time-dependent increase in these proteins in mitochondrial fractions. Functional studies demonstrated that NDUFB3 knockdown significantly rescued OGD/R-induced mitochondrial dysfunction, as indicated by restored ATP production, reduced ROS generation, and stabilized ΔΨm. Furthermore, NDUFB3 silencing attenuated apoptosis by inhibiting JNK phosphorylation and decreasing BAX levels. Conversely, overexpression of NDUFB3 alone was sufficient to induce mitochondrial abnormalities, including loss of ΔΨm and elevated oxidative stress in highly differentiated PC12 cells. Conclusions: Ischemic injury triggers the upregulation of mitochondrial complex subunits NDUFA4 and NDUFB3. While this may initially act as a compensatory response, our findings identify NDUFB3 as a critical mediator of ischemic stroke pathology, whose overexpression drives mitochondrial dysfunction and apoptosis. In contrast, the suppression of NDUFB3 provides protection against ischemic injury. Therefore, NDUFB3 may be a potential candidate therapeutic target for reducing mitochondrial damage in ischemic stroke, but this role requires further validation in additional experimental and translational models. Full article

Objective: Cerebral ischemia/reperfusion (I/R) injury triggers oxidative stress, neuroinflammation, neuronal degeneration, and white matter damage not only in directly affected cerebral regions but also in remote brain areas such as the cerebellum. Skimmianine, a naturally occurring furoquinoline alkaloid, has been reported to possess antioxidant and anti-inflammatory properties. This study investigated the protective effects of skimmianine pretreatment against secondary cerebellar injury following experimental cerebral I/R. Materials and Methods: Thirty-two female Wistar rats were randomly assigned to sham, Skimmianine, I/R, and I/R + Skimmianine groups (n = 8/group). Cerebral I/R was induced by transient middle cerebral artery occlusion for 60 min followed by 23 h reperfusion. Skimmianine (40 mg/kg/day, intraperitoneally) was administered for 14 days before ischemia induction. Oxidative stress markers, neuroinflammatory mediators, histopathological alterations, behavioral outcomes, and ultrastructural changes were evaluated. In addition, network pharmacology and molecular docking analyses were performed to explore potential molecular mechanisms. Results: Cerebral I/R significantly decreased TAS levels compared with sham (0.89 ± 0.15 vs. 1.52 ± 0.18 mmol Trolox Eq/L) and increased TOS (15.60 ± 3.03 vs. 6.80 ± 1.41 µmol H₂O₂ Eq/L), OSI (17.48 ± 0.50 vs. 4.43 ± 0.47), TNF-α (68.4 ± 10.2 vs. 18.6 ± 4.4 pg/mL), Iba1 (41.3 ± 9.7 vs. 11.7 ± 1.6 pg/mL), and GFAP levels (334.5 ± 12.5 vs. 87.7 ± 9.5 ng/mL; all p < 0.001). I/R also impaired motor performance, as shown by increased beam crossing time (11.7 ± 2.2 vs. 4.8 ± 0.7 s) and grid foot fault rate (18.6 ± 4.0% vs. 3.4 ± 1.1%). Skimmianine pretreatment significantly improved these alterations, increasing TAS to 1.29 ± 0.20 mmol Trolox Eq/L and reducing TOS, OSI, TNF-α, Iba1, and GFAP levels to 9.20 ± 2.04, 7.07 ± 0.47, 34.9 ± 7.4, 24.2 ± 6.9, and 237.0 ± 7.9, respectively, compared with the untreated I/R group. Histopathological scores for Purkinje cell loss, edema, vascular congestion, and TNF-α expression were also significantly reduced by skimmianine. Quantitative TEM analysis showed that I/R reduced myelin thickness (0.29 ± 0.05 vs. 0.53 ± 0.07 µm), increased G-ratio values (0.75 ± 0.05 vs. 0.63 ± 0.04), and increased vacuolized fibers (24.70 ± 4.20% vs. 3.20 ± 1.10%), whereas skimmianine partially restored myelin thickness (0.42 ± 0.07 µm), reduced the G-ratio (0.68 ± 0.05), and decreased vacuolized fibers (11.20 ± 2.80%; p < 0.05 vs. I/R). Molecular docking demonstrated favorable binding between skimmianine and TNF-α, with a predicted binding energy of −6.953 kcal/mol. Conclusions: These findings indicate that skimmianine exerts neuroprotective effects against secondary cerebellar injury following cerebral I/R through coordinated modulation of oxidative stress, systemic neuroinflammatory responses, astroglial injury-associated pathways, and inflammation-related mechanisms. Full article

This study investigated the effects of different doses of ranolazine in a middle cerebral artery occlusion/reperfusion (MCAO-I/R) model by evaluating histopathological changes and serum Sirtuin 1 (SIRT1), Apela peptide (APELA), and Apelin-13 (APL13) levels. A total of 47 male Sprague Dawley rats (250 ± 20 g) were randomly assigned to five groups: Sham (n = 7), MCAO (n = 10), MCAO+RAN10 (n = 10), MCAO+RAN30 (n = 10), and MCAO+RAN50 (n = 10). MCAO-I/R was induced by transient filament occlusion of the right middle cerebral artery for 90 min followed by reperfusion. Ranolazine was administered intraperitoneally once daily for 21 days in the treatment groups. Serum SIRT1, APELA, and APL13 levels were measured using enzyme-linked immunosorbent assay (ELISA), and brain tissues were evaluated histopathologically for neuronal degeneration and apoptotic cell counts. Histopathological analysis revealed significant neuronal degeneration and increased apoptosis in the MCAO group compared with the Sham group. Ranolazine treatment did not demonstrate significant histopathological improvement compared with the untreated MCAO group. Among the treatment groups, the MCAO+RAN50 group showed higher apoptotic cell counts and lower serum biomarker levels than the other ranolazine-treated groups. Serum SIRT1, APELA, and APL13 levels were lowest in the MCAO+RAN50 group, with selected pairwise differences reaching statistical significance. Under the present experimental conditions, clear evidence of neuroprotection could not be demonstrated. None of the ranolazine-treated groups showed significant histopathological improvement compared with the untreated MCAO group. These findings indicate that higher-dose ranolazine was not associated with neuroprotection under the conditions of this study. However, given the limited sample size, absence of infarct volume analysis, lack of neurological functional assessment, and absence of tissue-level molecular validation, further studies are required to clarify the biological significance and potential clinical relevance of the observed biomarker changes. Full article

Background/Objectives: Carotid perivascular adipose tissue (PVAT) density on computed tomography angiography (CTA) is a noninvasive surrogate marker of local vascular inflammation, but its relevance to stroke etiology in a homogeneous cohort of patients undergoing mechanical thrombectomy (MT) remains unclear. Methods: We retrospectively analyzed 146 consecutive patients with acute ischemic stroke treated with MT for acute middle cerebral artery (MCA) occlusion between May 2018 and August 2024. Baseline CTA was used to quantify carotid PVAT density with two 2–3 mm² circular regions of interest per internal carotid artery (ICA), placed ≥1 mm from the vessel wall. Measurements were performed bilaterally, and the ICA ipsilateral to the occluded MCA was defined as the stroke-side ICA. Etiology was classified according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) system and grouped as large-artery atherosclerosis (LAA), cardioembolism (CE), and other/undetermined (OD/UD). Interobserver agreement was assessed using the intraclass correlation coefficient. Results: The mean age was 72.21 ± 12.39 years; 83.6% of patients achieved successful recanalization (mTICI ≥ 2b), and 47.9% had a favorable 90-day outcome (mRS ≤ 2). In the LAA subgroup (n = 38), ipsilateral PVAT density was significantly higher (less negative) than contralateral PVAT density (−64.24 ± 11.74 vs. −78.22 ± 9.13 HU; p < 0.001). Ipsilateral PVAT density differed significantly across TOAST groups (ANOVA p = 0.004), being higher in LAA than in CE (Δ = 11.19 HU; p = 0.003) and OD/UD (Δ = 9.54 HU; p = 0.004). ROC analysis showed modest discrimination for LAA versus non-LAA stroke (AUC 0.67, 95% CI 0.58–0.75), with an optimal cutoff of −79 HU (sensitivity 92.1%, specificity 40.7%). In multivariable logistic regression, higher ipsilateral PVAT density was independently associated with LAA etiology (per 1-HU increase: OR 1.048, 95% CI 1.018–1.079; p = 0.0016). PVAT density was not associated with recanalization success or 90-day functional outcome. Conclusions: In patients with acute MCA occlusion undergoing MT, higher carotid PVAT density on the stroke side was independently associated with LAA stroke etiology but had limited value for predicting MT success or short-term clinical outcome. Full article

We previously demonstrated that fatty acid-binding protein 3 (FABP3) is significantly upregulated in ischemic neurons, and its inhibition mitigates ischemic brain injury in mice and attenuates mitochondrial damage under rotenone-induced oxidative stress. These findings suggest a potential role for FABP3 in mitochondrial dysfunction in ischemic neurons, although the underlying mechanism remains unclear. In this study, we further investigated the role of FABP3 in mitochondrial injury and apoptosis in ischemic neurons. Our findings indicated that FABP3 deficiency significantly decreased infarct volume following middle cerebral artery occlusion/reperfusion (MCAO/R) in mice, improved cognitive and spontaneous activity deficits, and suppressed BAX activation and mitochondrial translocation, caspase-3 activation, and cytochrome c release. In HT22 cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R), FABP3 deficiency increased cell viability, reduced apoptosis, and alleviated the loss of mitochondrial membrane potential. Conversely, FABP3 overexpression further exacerbated mitochondrial dysfunction and apoptosis, effects that were partially reversed by the BAX inhibitor BAI1. Furthermore, FABP3 overexpression promoted abnormal mitochondrial lipid accumulation and increased lipid peroxidation. Both the mitochondria-targeted antioxidant MitoQ and the ferroptosis inhibitor Ferrostatin-1 alleviated FABP3 overexpression-induced mitochondrial damage and apoptotic signaling. Collectively, our findings suggest that FABP3 is an important promoter of cerebral ischemia–reperfusion injury. FABP3 may aggravate ischemic neuronal injury by promoting abnormal mitochondrial lipid accumulation and lipid peroxidation, thereby enhancing BAX-dependent mitochondrial apoptotic signaling. Targeting FABP3 may provide a potential therapeutic strategy for neuroprotection in ischemic stroke. Full article

Sodium tanshinone IIA sulfonate (STS) injection is clinically used to protect against cerebral ischemia–reperfusion injury (CIRI). This study aimed to establish physiologically based pharmacokinetic–pharmacodynamic (PBPK–PD) models for normal and CIRI rats and to quantitatively characterize the time–concentration–effect relationship, as well as disease-specific mechanistic differences. A middle cerebral artery occlusion rat model was established. STS was administered via the tail vein, and blood samples were collected at serial time points. High-performance liquid chromatography and enzyme-linked immunosorbent assay were used to quantify plasma STS concentrations and inflammatory markers, respectively, whereas equilibrium dialysis was performed to determine protein binding. PK-Sim and Python were used to establish a PBPK model, which was subsequently extrapolated to humans to construct PBPK–PD models. The results showed that plasma STS concentrations were consistently higher in the model rats than in normal rats. STS significantly reduced inflammatory levels in model rats, with a delayed onset of pharmacological effect. Human PBPK model simulations indicated that STS is rapidly eliminated in healthy individuals, while its elimination is reduced under pathological conditions. This study provides a robust modeling framework and methodological reference for dose optimization and prediction of clinical efficacy of STS in the treatment of CIRI. Full article

Background: Anterior cranial fossa dural arteriovenous fistulas (ACF DAVFs) usually receive ethmoidal dural supply. Pial arterial supply has been described in intracranial DAVFs, including ACF DAVFs, but a dominant orbitofrontal pial feeder can create diagnostic overlap with mixed pial-dural arteriovenous malformation and make endovascular treatment hazardous. Case Presentation: A 75-year-old man with atrial fibrillation presented with right middle cerebral artery occlusion and underwent intravenous thrombolysis followed by mechanical thrombectomy. During right internal carotid angiography, transient arterial-phase opacification of a contralateral frontal draining vein through the anterior communicating artery prompted post-recanalization angiography. A high-grade left ACF DAVF was diagnosed, with dominant supply from the left orbitofrontal artery, minor anterior ethmoidal supply, two venous drainage routes, cortical venous reflux, and a varix. Although the DAVF was incidental to the ischemic presentation, it was considered to require treatment because of high-risk angioarchitecture, including Borden type III/Cognard type IV drainage, cortical venous reflux, and venous ectasia. No intraparenchymal nidus or normal venous-phase use of the refluxing veins was identified. Because pial transarterial access and complete transvenous closure were considered unsafe or uncertain, microsurgical draining-vein disconnection was performed. Postoperative angiography confirmed complete obliteration. Conclusions: In this case, microsurgical disconnection achieved angiographic cure, and the patient was transferred for rehabilitation with a modified Rankin Scale score of 1. The central diagnostic and therapeutic issue in pial-feeder-dominant ACF DAVF is not rarity alone, but angiographic differentiation from mixed pial-dural arteriovenous malformation and assessment of whether the shunt can be closed without compromising normal pial arteries or venous outflow. The thrombectomy angiogram provided the route to diagnosis, whereas pial arterial dominance and divided venous drainage determined the curative strategy. Full article

Pterostilbene (Pts), a small molecule stilbenoid and a dimethyl analogue of the star molecule resveratrol, exerts significant blood–brain barrier protection on cerebral ischemia-reperfusion injury and has received extensive attention. This study performed structural optimizations on Pts to obtain a series of derivatives and investigated their anti-ischemic activities both in vitro and in vivo, aiming to identify candidates with high safety and improved efficacy compared with Pts. The ADMET method was used to predict the drug-likeness of a series of Pts derivatives, and in vitro MTT cell viability analysis was conducted on neuroblastoma cells (SH-SY5Y) and brain microvascular endothelial cells (BMECs) after oxygen-glucose deprivation/reperfusion (OGD/R) injury. On the basis of the cytotoxicity results, four derivatives (NO. 1, NO. 3, NO. 5, and NO. 7) were selected for subsequent in vitro and in vivo biological activities evaluation. These compounds exhibited significantly higher TI values (18.29–30.61) in OGD/R-injured hBMECs compared with Pts (7.63) and effectively suppressed apoptosis, promoted cell migration, and enhanced tube formation capacity. In vivo, NO. 3 (5 mg/kg, ip., 7 d) demonstrated superior efficacy compared to Pts in improving cerebral blood flow, reducing infarction volume, enhancing neurological function, and modulating serum biomarker levels in middle cerebral artery occlusion/reperfusion (MCAO/R) rats, whereas NO. 1 and NO. 7 showed comparable efficacy to Pts. The acute intraperitoneal toxicity of NO. 3 was conducted and showed that the LD₅₀ of NO. 3 was estimated to be more than 300 mg/kg. In this study, the rational design and comprehensive evaluation of Pts derivatives were reported. Compound NO. 3 demonstrated superior pharmacological efficacy to Pts both in vitro and in vivo, and it may be a promising therapeutic candidate for ischemic stroke intervention. Full article