Abstract Background Microglial lipid handling and mitochondrial failure contribute to brain injury after subarachnoid hemorrhage (SAH), but the lipid signals coupling these processes remain unclear. We investigated whether linoleic acid (LA) restores microglial homeostasis through lysophosphatidylglycerol 16:0 (LPG[16:0]) and peroxisome proliferator-activated receptor-δ (PPARδ). Methods Case-control CSF metabolomics included 30 patients with aneurysmal SAH and 10 controls. Mechanisms were examined in a blood-injection mouse model and hemoglobin-exposed primary mouse microglia using targeted lipidomics, RNA sequencing, mitochondrial and phagocytosis assays, pharmacological perturbation, fractionation, coimmunoprecipitation, thermal shift analysis, and structural modeling. Behavioral outcomes were evaluated by open- field, Y-maze, and Morris water-maze testing. Results CSF LA concentrations were higher in patients with SAH than in controls and discriminated the groups within this cohort (area under the curve, 0.9967 [95% CI, 0.9859–1.000]; P<0.001). LA attenuated inflammatory activation and restored phagocytosis, mitochondrial membrane potential, respiration, and ATP production in hemoglobin-exposed microglia. LA restored PLA2G15-associated LPG(16:0) levels, which phenocopied these effects. Transcriptomic and inhibitor analyses identified PPARδ as a downstream effector. LPG(16:0) increased PPARδ stability, and fractionation and protease protection identified a PPARδ pool on the cytosolic face of the outer mitochondrial membrane. PPARδ associated with PLIN2 and CPT1A, promoted lipid droplet–mitochondria apposition, and supported fatty acid oxidation. In mice, LA reduced neuroinflammatory injury and partially improved anxiety- related behavior and spatial memory. Conclusions The LA–LPG(16:0)–PPARδ axis links glycerophospholipid remodeling to organelle coupling and mitochondrial recovery in microglia after SAH. The preventive dosing paradigm requires validation in clinically relevant treatment settings.

Subarachnoid hemorrhage (SAH) is a type of stroke mainly caused by the bursting of brain aneurysms, releasing iron ions into the subarachnoid space and subsequently inducing ferroptosis. Despite the utilization of various ferroptosis-inhibiting pharmacological agents to enhance neurological outcomes post-SAH, challenges such as inadequate targeting and suboptimal drug utilization persist. In response to these limitations, we have developed a novel spatiotemporal cascade reaction liposome that recombinant proteins incorporating neuron-targeting peptides and the functional structural domain of ferroptosis suppressor protein 1 (FSP1) were immobilized on the external surface of liposomes, which were internally loaded with coenzyme Q10 (CoQ10) to construct FSP1-Lipo-CoQ10.The purpose of this study is to investigate the neuroprotective effects of FSP1-Lipo-CoQ10 following SAH. As a result, FSP1-loaded liposomes enable targeted delivery to neurons in the lesion area and increase FSP1 levels on the cell membrane. Among the three liposomal formulations, FSP1-Lipo-CoQ10 demonstrated the most potent anti-ferroptosis effects and the greatest improvement in neurological function. FSP1-Lipo-CoQ10 provides a new approach for the therapeutic management of ferroptosis post-SAH and ameliorates associated pathological conditions.

Background Neonates and infants presenting for surgery experience not only pain but also heightened pain sensitivity due to immaturity of the nervous system, which may increase the risk of neurodevelopmental disorders. Improving awareness, assessment, and timely intervention of pediatric postoperative pain is critical.Methods Neonates and infants aged 0–12 months who underwent abdominal and/or sacroperineal surgeries between September 2022 and July 2023 were randomly assigned to a treatment group (oral paracetamol suspension, 0.1 mL/kg [10 mg/kg] administered every 6 hours for four doses after recovery from general anesthesia) or a control group (oral sterile water, 0.1 mL/kg). The primary outcome was postoperative pain intensity. Secondary outcomes included changes in liver and kidney function indices—aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine (Cr)—measured preoperatively and 48 hours postoperatively.Results A total of 220 neonates and infants were included. Postoperative pain scores were significantly lower in the treatment than in the control group at each time point at all assessed time points (1, 6, 12, 18, 24, 36, and 48 hours after recovery from general anesthesia, p<0.001). No significant differences were observed between groups in changes in AST, ALT, BUN, or Cr levels from baseline to 48 hours postoperatively.Conclusions Repeated oral administration of paracetamol after recovery from general anesthesia effectively reduces postoperative pain in neonates and infants without adversely affecting hepatic or renal function. This approach is safe and suitable for routine clinical use.Trial registration number NCT05564819.

Background:Neonates and infants presenting for surgery experience not only pain but also heightened pain sensitivity due to immaturity of the nervous system, which may increase the risk of neurodevelopmental disorders. Improving awareness, assessment, and timely intervention of pediatric postoperative pain is critical. Methods:Neonates and infants aged 0-12 months who underwent abdominal and/or sacroperineal surgeries between September 2022 and July 2023 were randomly assigned to a treatment group (oral paracetamol suspension, 0.1 mL/kg [10 mg/kg] administered every 6 hours for four doses after recovery from general anesthesia) or a control group (oral sterile water, 0.1 mL/kg). The primary outcome was postoperative pain intensity. Secondary outcomes included changes in liver and kidney function indices-aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine (Cr)-measured preoperatively and 48 hours postoperatively. Results:A total of 220 neonates and infants were included. Postoperative pain scores were significantly lower in the treatment than in the control group at each time point at all assessed time points (1, 6, 12, 18, 24, 36, and 48 hours after recovery from general anesthesia, p<0.001). No significant differences were observed between groups in changes in AST, ALT, BUN, or Cr levels from baseline to 48 hours postoperatively. Conclusions:Repeated oral administration of paracetamol after recovery from general anesthesia effectively reduces postoperative pain in neonates and infants without adversely affecting hepatic or renal function. This approach is safe and suitable for routine clinical use. Trial registration number:NCT05564819.

Gut microbiota dysbiosis is implicated in Alzheimer's disease (AD), but causal evidence and mechanisms linking it to microglial dysfunction remain unclear. This study aimed to determine whether gut microbiota drives neuroinflammation and cognitive impairment via the microglial TREM2/SYK signaling axis in early AD. Using six-month-old APP/PS1 mice, fecal microbiota transplantation (FMT) was performed between AD and wild-type mice. Cognitive function, gut microbiota composition (16S rRNA sequencing), serum metabolites, hippocampal neuroinflammation, microglial polarization, and TREM2/SYK/NF-κB pathway activity were assessed. BV2 microglial cells were treated with Aβ oligomers, a TREM2 agonist, or a SYK inhibitor for mechanistic validation. AD mice exhibited cognitive decline, reduced microbial diversity (e.g., decreased Bacteroidetes and Lactobacillus), and altered circulating metabolites, including decreased butyrate and elevated LPS. Their hippocampi exhibited heightened glial activation, elevated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and a shift toward pro-inflammatory activation markers (M1-associated). At the molecular level, TREM2 expression was downregulated, whereas SYK phosphorylation and NF-κB activation were enhanced, concomitant with synaptic protein loss. Critically, FMT from healthy donors reversed these abnormalities and improved cognition, whereas AD microbiota induced mild pathology in wild-type mice. In vitro, TREM2 activation or SYK inhibition attenuated Aβ-induced M1 polarization and cytokine release in microglia. Gut microbiota dysbiosis promotes early AD pathogenesis by dysregulating the microglial TREM2/SYK/NF-κB pathway, thereby driving neuroinflammation and synaptic dysfunction. Targeting this microbiota-signaling axis may offer novel therapeutic strategies.

Subarachnoid hemorrhage (SAH) results in the accumulation of blood in the subarachnoid space, which can trigger inflammatory responses and oxidative damage, thereby exacerbating secondary brain injury. Microglia play a critical role in clearing hematomas and cellular debris during pathological recovery. This study aimed to investigate the regulatory role of SIRT2 in phagocytic function and its potential mechanisms. The SAH model of endovascular perforation in Sprague-Dawley (SD) rats and in vitro model of primary microglia culture with Oxygenated hemoglobin (OxyHb) stimulation were used. Flow cytometry, Western blot, immunofluorescence, ELISA were used to detect the microglial phagocytic ability, expressions of SRIT2 and LC3-associated phagocytosis (LAP)-related proteins. Molecular docking, and immunoprecipitation were used to explore the underlying mechanism of the SIRT2/NRF2/CD36 signaling pathway. Behavioral experiments were conducted to evaluate changes in neurological function. Within 24 h after SAH, the expression of SIRT2 in brain and microglia was significantly increased, while the phagocytic ability and the expression of LAP-related proteins Rubicon, NOX2 were decreased. After inhibiting SIRT2, microglial LAP function was enhanced and the phagocytic index was increased. Mechanistically, SIRT2 inhibited NRF2 nuclear translocation by deacetylation, thereby downregulating CD36 expression and suppressing microglia LAP. ML385 reversed the enhancement of LAP and the improvement in neurological function induced by SIRT2 inhibition. SIRT2 suppresses microglial LAP by deacetylating NRF2, thereby impairing its nuclear translocation and reducing transcriptional expression of CD36 subsequently. Inhibiting SIRT2 may effectively enhance microglial LAP function via activating NRF2/CD36 pathway, promoting blood clearance and improving neurological prognosis after SAH.

OBJECTIVE:The pathophysiological distinctions and modifiable risk factors underlying ischemic versus hemorrhagic conversion in moyamoya disease (MMD) remain incompletely characterized, hindering subtype-specific management. This study aimed to delineate subtype-specific risk patterns and validate biomarkers for asymptomatic progression. METHODS:The authors analyzed the medical records of 774 adult MMD patients from Nanjing Jinling Hospital (2010-2020) and Nanjing Drum Tower Hospital (2013-2020). MMD was stratified as asymptomatic (n = 139), ischemic (n = 450), or hemorrhagic (n = 185). Multivariable logistic regression and Cox proportional hazards models were used to evaluate metabolic profiles, angiographic features (posterior cerebral artery [PCA] involvement and choroidal and lenticulostriate anastomoses), and longitudinal outcomes. RESULTS:Symptomatic patients demonstrated higher PCA involvement prevalence versus asymptomatic patients (p < 0.001). Ischemic MMD was independently associated with male sex (OR 2.00, 95% CI 1.30-3.07; p = 0.002), hypertension (OR 2.30, 95% CI 1.49-3.54; p < 0.001), hypertriglyceridemia (OR 1.36, 95% CI 1.01-1.83; p = 0.04), hyperglycemia (OR 1.22, 95% CI 1.03-1.45; p = 0.02), and PCA involvement (OR 2.43, 95% CI 1.40-4.20; p = 0.001). Hemorrhagic MMD correlated with BMI (OR 0.88 per kg/m2, 95% CI 0.81-0.97; p = 0.007), hypercholesterolemia (OR 1.53, 95% CI 1.14-2.07; p = 0.005), choroidal anastomosis formation (OR 2.38, 95% CI 1.21-4.70; p = 0.01), and PCA involvement (OR 3.41, 95% CI 1.76-6.61; p < 0.001). During the median 44-month follow-up, asymptomatic patients with PCA involvement (adjusted hazard ratio [HR] 4.86, 95% CI 1.07-22.14; p = 0.04) or choroidal anastomosis (adjusted HR 5.92, 95% CI 1.27-27.62; p = 0.02) exhibited an elevated risk of symptomatic conversion. CONCLUSIONS:Ischemic MMD was independently associated with male predominance, hypertension, and dyslipidemia, while hemorrhagic transformation correlated with lower BMI, hypercholesterolemia, and choroidal anastomosis. PCA involvement and choroidal anastomosis emerged as critical biomarkers for asymptomatic risk stratification.

Subarachnoid hemorrhage (SAH) is a type of stroke with a high disability and mortality rate. Apoptosis caused by massive damage to mitochondria in neuron cells and inflammatory responses caused by high extracellular ATP lead to poor outcomes. USP30 is a deubiquitinating enzyme that inhibits mitophagy, resulting in a failure to remove damaged mitochondria in a timely manner after SAH; nevertheless, the pathway through which USP30 inhibits mitophagy is unknown. This study evaluated the neuroprotective role and possible molecular basis by which inhibiting USP30 to attenuate SAH-induced EBI by promoting neuronal mitophagy. We used an in vitro model of hemoglobin exposure and an in vivo model of intravascular perforation. Increased expression of USP30 was found after SAH in vivo and in vitro, and USP30 inhibition expression in SAH mice treated with MF094 resulted in significant improvement of neurological injury and inflammatory response and mediated good outcomes, suggesting a neuroprotective effect of USP30 inhibition. In cultured neurons, inhibition of USP30 promoted ubiquitination modification of mitochondrial fusion protein 2 (MFN2) by E3 ubiquitin ligase (Parkin), separating damaged mitochondria from the healthy mitochondrial network and prompting mitophagy, causing early clearance of damaged intracellular mitochondria, and reducing the onset of apoptosis. The high extracellular ATP environment was meliorated, reversing the conversion of microglia to a pro-inflammatory phenotype and reducing inflammatory injury. USP30 inhibition had no autophagy-promoting effect on structurally and functionally sound mitochondria and did not inhibit normal intracellular ATP production. The findings suggest that USP30 inhibition has a neuroprotective effect after SAH by promoting early mitophagy after SAH to clear damaged mitochondria.

Background: Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular disease with high incidence and mortality rates, often associated with aneurysm rupture. Neuroinflammation, primarily mediated by microglial activation, is a critical process in the secondary injury following SAH. Despite extensive research, current Western medicine treatments have shown limited efficacy in mitigating neuroinflammation caused by microglia. In contrast, traditional Chinese medicine has garnered increasing attention for its anti-inflammatory properties. Isoorientin, a flavonoid compound, has demonstrated anti-inflammatory and antioxidant effects in various diseases. We hypothesize that isoorientin may inhibit microglia-induced neuroinflammation after SAH through the AKT/GSK3(3 pathway. Purpose: To elucidate whether isoorientin can regulate neuroinflammation following subarachnoid hemorrhage via the AKT/GSK3(3 pathway. Methods: We established in vitro and in vivo SAH models using hemoglobin and blood injection methods, respectively. The regulatory effects of isoorientin on neuroinflammation were investigated using Western blotting (WB), quantitative polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining (IF). Network pharmacology and molecular docking studies were conducted to explore the potential mechanisms. Additionally, the AKT inhibitor (MK2206) was employed to investigate its effects on the AKT/GSK3(3 pathway and neurological function after SAH. Neuroprotective effects were assessed using neurological function scores, open field tests, and rotarod tests. Results: Isoorientin significantly inhibited the mRNA expression levels of pro-inflammatory cytokines (TNF-alpha, IL-1(3, and IL-6) and promoted the expression levels of anti-inflammatory cytokines (CD206, IL-4, and IL-10). It facilitated the transformation of microglia from the M1 (pro-inflammatory) to the M2 (anti-inflammatory) phenotype. Further experiments revealed that isoorientin increased the expression of p-AKT protein in microglial cells, leading to the inactivation of GSK3(3 and upregulation of p-GSK3(3 protein, thereby suppressing neuroinflammation. However, these effects were reversed upon the addition of the AKT inhibitor (MK2206). In vivo experiments demonstrated that isoorientin improved short-term neurological functions, including motor functions, balance, and coordination abilities. Conclusion: This study provides compelling evidence that isoorientin exerts neuroprotective effects by regulating the AKT/GSK3(3 pathway, which may play a crucial role in mitigating neuroinflammation and neurological dysfunction after SAH. Isoorientin holds promise as a valuable therapeutic candidate for SAH treatment.

Ventriculoperitoneal shunting (VPS) helps reduce intracranial pressure and alleviate clinical symptoms caused by hydrocephalus in hemorrhagic Moyamoya disease (MMD). To date, no literature describes the occurrence of subdural fluid collection (SDFC) in hemorrhagic MMD patients undergoing VPS prior to cerebral revascularization. This report aims to explore the potential pathological mechanisms underlying SDFC following cerebral revascularization after prior VPS, and to provide effective strategies for future prevention. Clinical data of hemorrhagic MMD patients undergoing VPS prior to bypass admitted to our hospital from 2021 January and 2024 December were selected. Medical records were reviewed to analyze patient characteristics and the entire disease course. Among the 7 patients (9 cases), postoperative SDFC occurred in 7 cases (7/9, 77.8

BACKGROUNDS AND AIMS:Cytomegalovirus (CMV) is involved in the pathogenesis and progression of biliary atresia (BA). The immediate-early (IE) protein, the earliest and abundantly expressed viral protein following CMV infection, serves as an indicator of active viral replication when upregulated. This study aimed to investigate the expression and distribution of CMV-IE in liver tissues of BA and to evaluate their impact on postoperative prognosis following Kasai portoenterostomy (KPE). METHODS:This was a retrospective study in which clinical data from BA patients who underwent KPE were collected and analyzed. Preoperative variables included baseline demographics, serum biochemical indices, serologic CMV-IgM, blood and urine CMV-DNA, and liver fibrosis score. Prognostic endpoints included the jaundice clearance (CJ) rate within 3 months postoperatively, episode of cholangitis within 6 months postoperatively, and native liver survival (NLS) at 2 years postoperatively. Immunohistochemical staining of liver tissues was performed to assess the expression of CMV-IE and cytokeratin 19 (CK19). According to whether CMV-IE was detectable within CK19-positive areas, patients were categorized into three groups: bile duct involved group, bile duct non-involved group, and CMV-IE negative group. We compared liver function at the time of KPE and prognosis after KPE among the three groups. RESULTS:Among 102 BA patients, 63 were CMV-IE negative and 39 were CMV-IE positive. 89 patients underwent both serologic CMV antibody testing and hepatic CMV-IE detection. Among the 28 patients with serum CMV-IgM+, 18 patients (64.3 %) showed positive expression of CMV-IE in liver tissue. Among the 61 patients with serum CMV-IgM-, 19 cases (31.1 %) had positive CMV-IE expression in liver tissue. 75 patients had both hepatic CMV-IE expression and CMV-DNA testing (serum or urine) results, of 17 patients with CMV-DNA+, 8 (47.1 %) had hepatic CMV-IE expression, among 58 patients with CMV-DNA-, 20 (34.5 %) were positive for hepatic CMV-IE expression. Based on CMV-IE expression within CK19 positive regions or not, the 39 CMV-IE positive cases were further subdivided into bile duct involved group (n = 9) and bile duct non-involved group (n = 30). Compared with the bile duct non-involved group and the CMV-IE negative group, patients in the bile duct involved group had significantly older age at surgery, more referral times, higher preoperative alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and higher aspartate aminotransferase-to-platelet ratio index (APRi) (all P < 0.05). In addition, the bile duct involved group exhibited more severe liver fibrosis at KPE, lower jaundice clearance rate at 3 months post-KPE, higher incidence of postoperative cholangitis, and reduced native liver survival rates after KPE (all P < 0.05). CONCLUSION:Immunohistochemical detection of hepatic CMV-IE provides a more direct reflection of CMV infection in liver tissue. CMV-IE expression in cholangiocytes was significantly associated with older age at surgery, more severe hepatic injury, and poorer prognosis.

BackgroundSerum bilirubin levels are associated with the prognosis of spontaneous intracerebral hemorrhage (sICH). However, the specific predictive value of the indirect-to-total bilirubin (IBIL/TBIL) ratio in patients undergoing surgical hematoma evacuation remains unclear. This study aimed to investigate the association between the admission IBIL/TBIL ratio and 3-month functional outcomes.MethodsWe retrospectively analyzed 168 sICH patients who underwent surgical intervention between January 2024 and December 2025. The primary predictor was the admission IBIL/TBIL ratio. The primary outcome was the 3-month functional outcome, evaluated using the utility-weighted modified Rankin Scale (uw-mRS). Multivariable linear regression and restricted cubic spline (RCS) models were utilized to assess the independent and non-linear associations. Receiver operating characteristic (ROC) curves were generated to compare predictive performances.ResultsMultivariable regression analysis demonstrated that a higher IBIL/TBIL ratio was independently associated with improved functional outcomes [ln(uw-mRS + 1)] after adjusting for age, admission NIHSS score, initial hematoma volume, brain herniation, and secondary intraventricular hemorrhage (overall model p < 0.001). The RCS analysis showed an approximately linear relationship between the IBIL/TBIL ratio and functional recovery (P non-linearity = 0.568). The IBIL/TBIL ratio showed modest discrimination for 3-month poor functional outcome (mRS 4–6; AUC = 0.655), higher than TBIL alone (AUC = 0.504) but lower than the admission NIHSS score (AUC = 0.784).ConclusionThe admission IBIL/TBIL ratio is linearly and independently associated with 3-month functional outcome in sICH patients following surgical evacuation. As an inexpensive and routinely available biomarker, it may serve as an adjunctive prognostic indicator, but it should not be interpreted as a standalone replacement for established clinical severity measures.

Background: Subarachnoid hemorrhage (SAH) represents a severe subtype of hemorrhagic stroke and is associated with unfavorable clinical outcomes. Physical exercise is an effective behavioral intervention that reduces the risk of stroke and preserves neurological function. Whole-body vibration (WBV) is a straightforward form of physical exercise that requires minimal motor skill proficiency. It has positive effects on neuromuscular performance and cardiovascular responses. Methods: The present study aims to investigate the potential protective effects of WBV on SAH-induced brain damage and neurological dysfunction in rats. WBV was administered using a vibration platform, with animals stimulation at 30 Hz for two sessions per day over a 30-day period. A modified endovascular perforation technique was employed to establish the in vivo SAH model. Results: WBV markedly decreased SAH-induced brain edema and inhibited levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) and MitoSOX, two markers of oxidative stress. Immunostaining analyses demonstrated that WBV significantly attenuated microglial activation (at 24 and 72 h) and astrocytic activation (at 24 h) in the cortical region following SAH. Consistently, WBV markedly inhibited the expression of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), in brain tissue and serum. WBV pretreatment significantly inhibited cortical neuronal apoptosis and downregulated caspase-1 activation at 24 h post-SAH. In addition, WBV activated Sirt3 following SAH, and its protective effects were partially prevented by the Sirt3 inhibitor 3-TYP. Conclusions: Our present data indicate that WBV is a clinically potent strategy that protects against the SAH-induced brain damage and neurological dysfunction by regulating Sirt3 and neuroinflammation.

BACKGROUND:Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular disease with high incidence and mortality rates, often associated with aneurysm rupture. Neuroinflammation, primarily mediated by microglial activation, is a critical process in the secondary injury following SAH. Despite extensive research, current Western medicine treatments have shown limited efficacy in mitigating neuroinflammation caused by microglia. In contrast, traditional Chinese medicine has garnered increasing attention for its anti-inflammatory properties. Isoorientin, a flavonoid compound, has demonstrated anti-inflammatory and antioxidant effects in various diseases. We hypothesize that isoorientin may inhibit microglia-induced neuroinflammation after SAH through the AKT/GSK3β pathway. PURPOSE:To elucidate whether isoorientin can regulate neuroinflammation following subarachnoid hemorrhage via the AKT/GSK3β pathway. METHODS:We established in vitro and in vivo SAH models using hemoglobin and blood injection methods, respectively. The regulatory effects of isoorientin on neuroinflammation were investigated using Western blotting (WB), quantitative polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining (IF). Network pharmacology and molecular docking studies were conducted to explore the potential mechanisms. Additionally, the AKT inhibitor (MK2206) was employed to investigate its effects on the AKT/GSK3β pathway and neurological function after SAH. Neuroprotective effects were assessed using neurological function scores, open field tests, and rotarod tests. RESULTS:Isoorientin significantly inhibited the mRNA expression levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and promoted the expression levels of anti-inflammatory cytokines (CD206, IL-4, and IL-10). It facilitated the transformation of microglia from the M1 (pro-inflammatory) to the M2 (anti-inflammatory) phenotype. Further experiments revealed that isoorientin increased the expression of p-AKT protein in microglial cells, leading to the inactivation of GSK3β and upregulation of p-GSK3β protein, thereby suppressing neuroinflammation. However, these effects were reversed upon the addition of the AKT inhibitor (MK2206). In vivo experiments demonstrated that isoorientin improved short-term neurological functions, including motor functions, balance, and coordination abilities. CONCLUSION:This study provides compelling evidence that isoorientin exerts neuroprotective effects by regulating the AKT/GSK3β pathway, which may play a crucial role in mitigating neuroinflammation and neurological dysfunction after SAH. Isoorientin holds promise as a valuable therapeutic candidate for SAH treatment.

Missing MRI sequences due to limited scan time, image artifacts, scan corruption, allergies to contrast agents, etc. in real clinical environments limit the availability of deep learning (DL) brain tumor segmentation models. Currently, there is no systematic evaluation of the impact of missing sequences on DL-based brain tumor segmentation models, nor is there a unified approach to address these diverse scenarios. We proposed a pipeline for brain tumor segmentation in various MRI sequence missing scenarios. A novel unpaired multi-modal generative adversarial transformer (UMMGAT) was designed to perform image-to-image translation among MRI sequences from the BRATS dataset (335 cases) and local dataset (92 cases). The generated images were then used to replace missing ones as inputs for a multi-modal segmentation network. The UMMGAT can be effectively trained with unpaired data to perform arbitrary image-to-image translations among multi-center multi-sequence MR images. The median DSCs of the brain tumor segmentation are significantly improved by using generated images vs copied images under most of the scenarios. Notably, in scenarios where Flair, T1, T2, T1ce, Flair&T1ce, and T1&T1ce sequences were absent, using gFlair_from_T2 (generated Flair from T2), gT1_from_T2, gT2_from_T1, gT1ce_from_T1, gFlair_from_T2 & gT1ce_from_T1, and gT1_from_T2 & gT1ce_from_T2 vs using copied source sequences for substitution, the median DSCs of WT were 0.734(0.591 - 0.832) vs 0.554(0.341 - 0.689) , 0.905(0.774 - 0.927) vs 0.854(0.704 - 0.911) , 0.865(0.742 - 0.908) vs 0.781(0.515 - 0.888) , 0.894(0.794 - 0.917) vs 0.849(0.687 - 0.914) , 0.71(0.536 - 0.81) vs 0.436(0.144 - 0.615) , and 0.897(0.756 - 0.919) vs 0.721(0.512 - 0.858)(p<0.0001). The proposed UMMGAT can synthesize high-fidelity images through training on unpaired datasets. The generated images exhibit potential to enhance the DL brain tumor segmentation model in simulated sequence missing scenarios.

Ischemic stroke (IS) is a leading cause of death and disability worldwide, with complex pathophysiological mechanisms posing significant challenges to clinical treatment. In recent years, nanotechnology has shown broad prospects in the treatment of IS due to its excellent biocompatibility, high specific surface area, and outstanding drug loading capacity. This review systematically summarizes the progress of nanomaterials in IS treatment, focusing on their functional characteristics, targeting strategies, and controlled drug release technologies, aiming to optimize the design and functionality of nanomaterials to facilitate their transition from laboratory studies to clinical applications.

OBJECTIVE:Endovascular treatment (EVT) is considered an effective treatment for patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH). Although the prognosis of these patients seems to have improved in recent years, it is generally still considered poor. We analyzed our data to determine potential predictors of poor prognosis in these patients. METHODS:We retrospectively analyzed data from patients with poor-grade aSAH who underwent EVT at our institution between November 2018 and June 2023. The data included patient baseline clinical characteristics, treatment modalities, imaging features, postoperative complications, and functional neurological outcomes. At six months, outcomes were assessed using the modified Rankin scale (mRS) and dichotomized into good (mRS 0-2) and poor (mRS 3-6) groups. Multivariate analysis was performed to identify predictors of outcome, and the discriminative ability of the model was assessed using the area under the receiver operating characteristic curve (ROC). RESULTS:The study included 117 poor-grade aSAH patients who underwent EVT. Fifty-eight (49.6 %) patients had poor outcomes. Univariate analysis suggested that older age (p = 0.003), higher Hunt-Hess (H-H) grade (15.3 % vs. 46.6 %, p < 0.001), posterior circulation aneurysms (15.3 % vs.31.0 %, p = 0.050)hydrocephalus (39.0 % vs. 63.8 %, p = 0.010), intraventricular hematoma (IVH) (69.5 % vs. 87.9 %, p = 0.023), ventricular casting (8.5 % vs. 43.1 %, p < 0.001), and external ventricular drainage (EVD) (44.1 % vs. 77.6 %, p < 0.001) were associated with poor outcomes. Multivariate analysis revealed that older age, higher H-H grade, and ventricular casting were predictors of poor outcomes with good discriminative ability (ROC=0.81, 95 % CI 0.73-0.89; p < 0.001). CONCLUSIONS:Older age, higher H-H grade, and ventricular casting are associated with poor outcomes in patients with poor-grade aSAH. In this study, 50.4 % of patients achieved good outcomes, suggesting that early individualized treatment should be aggressively pursued for poor-grade aSAH patients to avoid rebleeding from ruptured aneurysms and potentially poor outcomes.

BACKGROUND:Subarachnoid hemorrhage (SAH) remains a serious public health problem worldwide, especially in economically developed regions/countries. This study intends to thoroughly analyze the incidence, mortality, and disability-adjusted life years (DALYs) rate of SAH at the global, regional, and national levels. This study focused on the differences in SAH incidence between China and Japan from 1990 to 2019, and projected global, Chinese, and Japanese SAH incidence rates until 2030. METHODS:Data on the disease burden owing to SAH from 1990 to 2019 were obtained from the Global Burden of Disease (GBD) Study 2019. linear regression analysis was used to calculate the estimated annual percentage change (EAPC) and linear regression method was used to calculate the average annual percentage change (AAPC). Bayesian age-period-cohort (BAPC) model was used to predict the disease burden from 2020 to 2030. RESULTS:Globally, age-standardised incidence, mortality, and DALYs rates was declined from 1990 to 2019. In 1990-2019, the incidence of SAH decreased in China, while it increased in Japan, especially among middle-aged and elderly women. Projections suggest that the global incidence of SAH will decrease by 2.06% in 2030, with an increase of 6.24% in China and 13.82% in Japan, with the highest increase among Japanese women being 16.19%. CONCLUSIONS:Global SAH incidence, mortality, and DALYs rates declined over the 1990-2019 period, with regional/national SAH mortality and DALYs rates negatively correlated with socio-demographic index (SDI), while SAH incidence was positively correlated with SDI. The incidence of SAH decreased in China and increased in Japan during this period. The predictions show that over the next 10 years, while the incidence of SAH continues to decline globally, the incidence of SAH in China and Japan has increased. Thus, SAH remains a serious disease burden that requires early intervention targeting risk factors and populations at risk that may have increased because of economic development.

Background Neuroinflammation participates in the pathogenesis of subarachnoid haemorrhage (SAH); however, no effective treatments exist. MicroRNAs regulate several aspects of neuronal dysfunction. In a previous study, we found that exosomal miR-486-3p is involved in the pathophysiology of SAH. Targeted delivery of miR-486-3p without blood-brain barrier (BBB) restriction to alleviate SAH is a promising neuroinflammation approach.Methods In this study, we modified exosomes (Exo) to form an RVG-miR-486-3p-Exo (Exo/miR) to achieve targeted delivery of miR-486-3p to the brain. Neurological scores, brain water content, BBB damage, flow cytometry and FJC staining were used to determine the effect of miR-486-3p on SAH. Western blot analysis, ELISA and RT-qPCR were used to measure relevant protein and mRNA levels. Immunofluorescence staining and laser confocal detection were used to measure the expression of mitochondria, lysosomes and autophagosomes, and transmission electron microscopy was used to observe the level of mitophagy in the brain tissue of mice after SAH.Results Tail vein injection of Exo/miR improved targeting of miR-486-3p to the brains of SAH mice. The injection reduced levels of neuroinflammation-related factors by changing the phenotype switching of microglia, inhibiting the expression of sirtuin 2 (SIRT2) and enhancing mitophagy. miR-486-3p treatment alleviated neurobehavioral disorders, brain oedema, BBB damage and neurodegeneration. Further research found that the mechanism was achieved by regulating the acetylation level of peroxisome proliferator-activated receptor γ coactivator l alpha (PGC-1α) after SIRT2 enters the nucleus.Conclusion Exo/miR treatment attenuates neuroinflammation after SAH by inhibiting SIRT2 expression and stimulating mitophagy, suggesting potential clinical applications.