Lower serum uric acid and impairment of right cerebral hemisphere structural brain networks are related to depressive symptoms in cerebral small vessel disease: A cross-sectional study.

Cerebral small vessel disease (SVD) may be associated with an increased risk of depressive symptoms. Serum uric acid (SUA), an antioxidant, may be involved in the occurrence and development of depressive symptoms, but the mechanism remains unknown. Moreover, the relationship between structural brain networks and SUA has not been explored. This study examined the relationship between SUA and depressive symptoms in patients with SVD using graph theory analysis. We recruited 208 SVD inpatients and collected fasting blood samples upon admission. Depressive symptoms were assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24). Magnetic resonance imaging was used to evaluate SVD, and diffusion tensor images were used to analyze structural brain networks using graph theory. Patients with depressive symptoms (n = 34, 25.76%) compared to those without (334.53 vs 381.28 µmol/L, p = 0.017) had lower SUA levels. Graph theoretical analyses showed a positive association of SUA with betweenness centrality, nodal efficiency, and clustering coefficients and a negative correlation with the shortest path length in SVD with depressive symptoms group. HAMD scores were significantly associated with nodal network metrics in the right cerebral hemisphere. Our findings suggested that lower SUA levels are significantly associated with disrupted structural brain networks in the right cerebral hemisphere of patients with SVD who have depressive symptoms.

Dl-3-n-Butylphthalide Alleviates Secondary Brain Damage and Improves Working Memory After Stroke in Cynomolgus Monkeys.

BACKGROUND: Remote secondary neurodegeneration is associated with poststroke cognitive impairment (PSCI). Dl-3-n-butylphthalide (NBP) improves PSCI clinically. However, whether it ameliorates PSCI by alleviating secondary neurodegeneration remains uncertain. Nonhuman primates provide more relevant models than rodents for human stroke and PSCI. This study investigated the effects of NBP on PSCI and secondary neurodegeneration in cynomolgus monkeys after permanent left middle cerebral artery occlusion (MCAO). METHODS: Thirteen adult male cynomolgus monkeys were randomly assigned to sham (n=4), MCAO+placebo (n=5), and MCAO+NBP groups (n=4). The MCAO+placebo and MCAO+NBP groups received saline and NBP injections intravenously, respectively, starting at 6-hour postsurgery for 2 weeks, followed by soybean oil and NBP orally, respectively, for 10 weeks after MCAO. Infarct size was assessed at week 4 by magnetic resonance imaging. Working memory and executive function were evaluated dynamically using the delayed response task and object retrieval detour task, respectively. Neuron loss, glia proliferation, and neuroinflammation in the ipsilateral dorsal lateral prefrontal cortex, thalamus, and hippocampus were analyzed by immunostaining 12 weeks after MCAO. RESULTS: Infarcts were located in the left middle cerebral artery region, apart from the ipsilateral dorsal lateral prefrontal cortex, thalamus, or hippocampus, with no significant difference between the MCAO+placebo and MCAO+NBP group. Higher success in delayed response task was achieved at weeks 4, 8, and 12 after NBP compared with placebo treatments (P<0.05), but not in the object retrieval detour task (all P>0.05). More neurons and less microglia, astrocytes, CD68-positive microglia, tumor necrosis factor-α, and inducible NO synthase were observed in the ipsilateral dorsal lateral prefrontal cortex and thalamus after 12 weeks of NBP treatment (P<0.05), but not in the hippocampus (P>0.05). CONCLUSIONS: Our findings indicate that NBP improves working memory by alleviating remote secondary neurodegeneration and neuroinflammation in the ipsilateral dorsal lateral prefrontal cortex and thalamus after MCAO in cynomolgus monkeys.

Body mass index and risk of inflammatory breast disease: a Mendelianrandomization study / Índice de masa corporal y riesgo de mastitis: un estudio de aleatorización mendeliana

Introduction: in previous studies, obesity was identified as a risk factor for inflammatory breast disease, but its causality is uncertain. In thepresent study, we performed a two-sample Mendelian randomization (TSMR) analysis to investigate the causal relationship between obesity andinflammatory breast disease.Methods: we use body mass index (BMI) as a measure of obesity. Data for single nucleotide polymorphisms (SNPs) associated with BMI wereobtained from UK Biobank. Data for single nucleotide polymorphisms (SNPs) associated with mastitis were obtained from FinnGen Biobank. We usedseveral MR analysis methods, such as inverse-variance weighting (IVW), MR-Egger, weighted median, simple mode and weighted mode to makeour results more convincing. We also performed MR-PRESSO test, MR-Egger test, heterogeneity test, pleiotropy test and leave-one-out analysisto make our analysis results more robust and credible. We used odds ratio (OR) to evaluate the causal relationship between BMI and mastitis.Results: based on the IVW random effects model, we found that a one-standard deviation (SD) increase in BMI increased the risk of mastitis by62.1 % (OR = 1.621, 95 % CI: 1.262-2.083, p = 1.59E-4), which is almost consistent with the results of several other methods.Conclusions: in European individuals, an increase in the number of BMI increases the risk of inflammatory breast disease. People with high BMIneed to control their weight to reduce the incidence of inflammatory breast disease.(AU)

Introducción: en estudios previos, la obesidad se identificó como un factor de riesgo para la enfermedad inflamatoria de mama, pero su cau-salidad es incierta. En el presente estudio, se realizó un análisis de aleatorización mendeliana de dos muestras (TSMR) para investigar la relacióncausal entre la obesidad y la enfermedad inflamatoria de mama.Métodos: se empleó el índice de masa corporal (IMC) como medida de obesidad. Los datos de los polimorfismos de nucleótido único (SNP)asociados con el IMC se obtuvieron del Biobank de Reino Unido y los datos de los polimorfismos de nucleótido único (SNP) asociados con lamastitis se obtuvieron de FinnGen Biobank. Se utilizaron varios métodos de análisis de RM, como la ponderación inversa de la varianza (IVW),RM-Egger, mediana ponderada, modo simple y modo ponderado para que nuestros resultados fueran más convincentes. También se realizaronla prueba MR-PRESSO, la prueba MR-Egger, la prueba de heterogeneidad, el test de pleiotropía y la validación dejando uno fuera (en inglés,leave-one-out) para que los resultados de nuestro análisis fueran más sólidos y creíbles. Se utilizó la odds ratio (OR) para evaluar la relacióncausal entre el IMC y la mastitis.Resultados: basándonos en el modelo de efectos aleatorios IVW, se halló que un aumento de una desviación estándar (DE) en el IMC aumentabael riesgo de mastitis en un 62,1 % (OR = 1,621, IC 95 %: 1,262-2,083, p = 1,59E-4), que es casi consistente con los resultados de otrosdiversos métodos.Conclusiones: en los individuos europeos, un aumento del número de IMC aumenta el riesgo de enfermedad inflamatoria mamaria. Las personascon un IMC elevado deben controlar su peso para reducir la incidencia de enfermedad inflamatoria de la mama.(AU)

Cerebral asymmetry in adult Macaca fascicularis as revealed by voxel-based MRI and DTI analysis.

Investigating cerebral asymmetries in non-human primates would facilitate to understand the evolutional traits of the human brain specialization related to language and other high-level cognition. However, brain asymmetrical studies of monkeys produced controversial results. Here, we investigated the cerebral asymmetries using a combination of the optimized voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) protocols in monkeys. The study-specific MRI and DTI-based templates were created in 66 adult Macaca fascicularis, and the asymmetrical index of grey and white matter was subsequently examined. The VBM analysis detected the well-known frontal and occipital petalias and confirmed the presence of leftward asymmetry in the ventral frontal cortex. A marked leftward asymmetry of anterior superior temporal gyrus but not posterior portion were found. We also identified grey matter asymmetries in some regions that were not previously reported including rightward anterior cingulate, insular cortex and thalamus, and leftward caudate. In contrast, the results of TBSS analysis for the first time revealed the robust leftwards asymmetries of corpus callosum (splenium and body), internal/external capsule, and white matter in middle temporal gyrus, adjacent thalamus and amygdala whereas the rightwards in uncinate fasciculus, posterior thalamic radiation and cerebral peduncle. These findings provide robust evidence of grey and white matter asymmetries in the brain of monkeys, which may extend the understanding of brain evolution in cerebral specialization.

Plaque characteristics associated with failure of primary balloon angioplasty for intracranial atherosclerotic stenosis: a retrospective study.

BACKGROUND: Primary balloon angioplasty (PBA) is an alternative treatment approach for intracranial atherosclerotic stenosis (ICAS); however, its efficacy may be compromised by arterial dissection or early elastic recoil after balloon dilation. This study aimed to explore the association between plaque characteristics on high-resolution magnetic resonance vessel wall imaging (HR-VWI) and failure of PBA for ICAS. METHODS: We conducted a retrospective analysis of 113 patients with ICAS who underwent HR-VWI before endovascular treatment. Based on the presence of arterial dissection or early elastic recoil post-balloon dilation, patients were classified into the failed PBA (FPBA) group or the successful PBA (SPBA) group. Clinical and baseline HR-VWI characteristics were compared between the two groups. Multivariable analysis was used to investigate plaque features associated with the failure of PBA. RESULTS: The FPBA and SPBA groups comprised 74 and 39 patients, respectively. Plaque eccentricity (83.78% vs 46.15%, P<0.001), negative remodeling (90.54% vs 48.72%, P<0.001), remodeling index (median 0.73 vs 0.90, P=0.001), and intraplaque hemorrhage (31.08% vs 5.13%, P=0.002) differed significantly between the FPBA and SPBA groups. Multivariable analysis indicated that higher frequency of plaque eccentricity (OR 14.03, 95% CI 3.42 to 57.62, P<0.001) and negative remodeling (OR 6.11, 95% CI 1.22 to 30.71, P=0.028) were independently associated with failure of PBA. CONCLUSION: Our findings showed that failure of PBA was associated with plaque eccentricity and negative remodeling. Analysis of plaque characteristics on baseline HR-VWI holds potential value for identifying arterial dissection or early elastic recoil after angioplasty in patients with ICAS.

Late-onset aspirin-related hemolysis and subsequent subdural hemorrhage in patient with glucose-6-phosphate dehydrogenase deficiency.

Key Clinical Message: Aspirin-related hemolysis in G6PD deficiency could be late-onset during long-term administration. Hemolytic anemia could continue for a relatively long time in elder patient with G6PD deficiency, which might be related to other adverse events. Abstract: Aspirin-related hemolysis in G6PD-deficient individuals was generally reported among patients who received high-dose supplements within several days after ingestion. The safety of long-term and low-dose (50-325 mg/day) aspirin in patients coexist G6PD deficiency and cardiovascular disease is neglected in clinical practice. In this case, we observed a late-onset hemolysis and subsequent fatal subdural hemorrhage in one G6PD-deficient individual who had received long-term and low-dose aspirin. An 83-year-old male was diagnosed with acute ischemic stroke and treated with 100 mg/day aspirin at the emergency room. After admission, the patient was diagnosed with severe G6PD deficiency based on enzyme activity, but no hemolysis occurred within 10-day aspirin therapy in the hospital. Hence, 100 mg/day aspirin was continued on discharge. Two months later, the patient presented acute hemolysis manifested as fatigue, dark urine, and moderate jaundice. Although hemolysis was self-limit in a few days, hemoglobin decline continued for 20 days until a fatal subdural hemorrhage occurred. Our study indicated aspirin-related hemolysis could be late-onset in G6PD-deficient individual even receiving low-dose treatment and is probably linked to subsequent major bleeding events.

Certification of stroke centers at primary hospitals and the improvement of thrombolysis n South China during 2020-2022.

INTRODUCTION: IVT use declined globally in 2020 due to the Corona Virus Disease 2019 (COVID-19) pandemic, but it increased in South China. This study was conducted to evaluate the association of establishing Stroke Prevention Centers (SPCs) at primary hospitals with IVT increase in South China. MATERIALS AND METHODS: We conducted a longitudinal observational study across 336 hospitals in 114 areas in South China during 2020-2022. Data regarding certified stroke centers, IVT volumes, and IVT rates were collected. Correlations between IVT rates and the number or density of stroke centers were accessed. IVT use was compared among areas with different levels of stroke centers or on different certification process. RESULTS: During 2020-2022, there were 83, 125, and 152 stroke centers, with 26, 65, and 92 SPCs, respectively. IVT therapies were 12,795, 17,266, and 20,411, representing a 29.8% increase/year (all p < 0.001). IVT rates increased from 7.2% in 2020 to 8.8% and 10.4% in 2021 and 2022, demonstrating a 22.2% increase/year (all p < 0.001). IVT rates correlated with the number and density of SPCs (all p < 0.05). IVT rates were higher in areas equipped with SPCs than in those without stroke centers (all p < 0.05). IVT rates consistently increased during the SPC certification process from 1 year before through the certification and subsequent maintenance (both p < 0.05). DISCUSSION AND CONCLUSION: Well-organised SPCs and IVT therapy demonstrated substantial increase during the 3-year period. Certification of SPCs at primary hospitals is associated with improved IVT therapy in South China even with city lockdown during COVID-19 pandemic.

Body mass index and risk of inflammatory breast disease: a Mendelian randomization study.

Introduction: Introduction: in previous studies, obesity was identified as a risk factor for inflammatory breast disease, but its causality is uncertain. In the present study, we performed a two-sample Mendelian randomization (TSMR) analysis to investigate the causal relationship between obesity and inflammatory breast disease. Methods: we use body mass index (BMI) as a measure of obesity. Data for single nucleotide polymorphisms (SNPs) associated with BMI were obtained from UK Biobank. Data for single nucleotide polymorphisms (SNPs) associated with mastitis were obtained from FinnGen Biobank. We used several MR analysis methods, such as inverse-variance weighting (IVW), MR-Egger, weighted median, simple mode and weighted mode to make our results more convincing. We also performed MR-PRESSO test, MR-Egger test, heterogeneity test, pleiotropy test and leave-one-out analysis to make our analysis results more robust and credible. We used odds ratio (OR) to evaluate the causal relationship between BMI and mastitis. Results: based on the IVW random effects model, we found that a one-standard deviation (SD) increase in BMI increased the risk of mastitis by 62.1 % (OR = 1.621, 95 % CI: 1.262-2.083, p = 1.59E-4), which is almost consistent with the results of several other methods. Conclusions: in European individuals, an increase in the number of BMI increases the risk of inflammatory breast disease. People with high BMI need to control their weight to reduce the incidence of inflammatory breast disease.

Introducción: Introducción: en estudios previos, la obesidad se identificó como un factor de riesgo para la enfermedad inflamatoria de mama, pero su causalidad es incierta. En el presente estudio, se realizó un análisis de aleatorización mendeliana de dos muestras (TSMR) para investigar la relación causal entre la obesidad y la enfermedad inflamatoria de mama. Métodos: se empleó el índice de masa corporal (IMC) como medida de obesidad. Los datos de los polimorfismos de nucleótido único (SNP) asociados con el IMC se obtuvieron del Biobank de Reino Unido y los datos de los polimorfismos de nucleótido único (SNP) asociados con la mastitis se obtuvieron de FinnGen Biobank. Se utilizaron varios métodos de análisis de RM, como la ponderación inversa de la varianza (IVW), RM-Egger, mediana ponderada, modo simple y modo ponderado para que nuestros resultados fueran más convincentes. También se realizaron la prueba MR-PRESSO, la prueba MR-Egger, la prueba de heterogeneidad, el test de pleiotropía y la validación dejando uno fuera (en inglés, leave-one-out) para que los resultados de nuestro análisis fueran más sólidos y creíbles. Se utilizó la odds ratio (OR) para evaluar la relación causal entre el IMC y la mastitis. Resultados: basándonos en el modelo de efectos aleatorios IVW, se halló que un aumento de una desviación estándar (DE) en el IMC aumentaba el riesgo de mastitis en un 62,1 % (OR = 1,621, IC 95 %: 1,262-2,083, p = 1,59E-4), que es casi consistente con los resultados de otros diversos métodos. Conclusiones: en los individuos europeos, un aumento del número de IMC aumenta el riesgo de enfermedad inflamatoria mamaria. Las personas con un IMC elevado deben controlar su peso para reducir la incidencia de enfermedad inflamatoria de la mama.

Loss of SARM1 ameliorates secondary thalamic neurodegeneration after cerebral infarction.

Ischemic stroke causes secondary neurodegeneration in the thalamus ipsilateral to the infarction site and impedes neurological recovery. Axonal degeneration of thalamocortical fibers and autophagy overactivation are involved in thalamic neurodegeneration after ischemic stroke. However, the molecular mechanisms underlying thalamic neurodegeneration remain unclear. Sterile /Armadillo/Toll-Interleukin receptor homology domain protein (SARM1) can induce Wallerian degeneration. Herein, we aimed to investigate the role of SARM1 in thalamic neurodegeneration and autophagy activation after photothrombotic infarction. Neurological deficits measured using modified neurological severity scores and adhesive-removal test were ameliorated in Sarm1-/- mice after photothrombotic infarction. Compared with wild-type mice, Sarm1-/- mice exhibited unaltered infarct volume; however, there were markedly reduced neuronal death and gliosis in the ipsilateral thalamus. In parallel, autophagy activation was attenuated in the thalamus of Sarm1-/- mice after cerebral infarction. Thalamic Sarm1 re-expression in Sarm1-/- mice increased thalamic neurodegeneration and promoted autophagy activation. Auotophagic inhibitor 3-methyladenine partially alleviated thalamic damage induced by SARM1. Moreover, autophagic initiation through rapamycin treatment aggravated post-stroke neuronal death and gliosis in Sarm1-/- mice. Taken together, SARM1 contributes to secondary thalamic neurodegeneration after cerebral infarction, at least partly through autophagy inhibition. SARM1 deficiency is a potential therapeutic strategy for secondary thalamic neurodegeneration and functional deficits after stroke.

Efficacy and safety of agomelatine versus SSRIs/SNRIs for post-stroke depression: a systematic review and meta-analysis of randomized controlled trials.

Agomelatine is effective in the treatment of depression, but its effect for post-stroke depression (PSD) remains unclear. This study was conducted to compare the efficacy and safety of agomelatine versus SSRIs/SNRIs in treating PSD. We systematically searched Embase, PubMed, Cochrane Library, WanFang Data, China National Knowledge Infrastructure, and Cqvip databases for double-blind randomized controlled studies comparing the efficacy and safety of agomelatine versus SSRIs/SNRIs for PSD until December 2022. The primary efficacy endpoint was the Hamilton Depression Rating Scale (HAMD) score, and the primary safety endpoint was the incidence of overall adverse reactions. Nine studies comprising 857 patients with PSD were included. After 6-12 weeks of treatment, the HAMD score ( P  = 0.16) and the overall response rates ( P  = 0.20) in the agomelatine group were comparable to that in the SSRIs/SNRIs group. Participants treated with agomelatine achieved higher Barthel Index scores compared with the SSRIs/SNRIs group ( P  = 0.02). There was a significantly lower incidence of overall adverse reactions ( P  = 0.008) and neurological adverse reactions ( P  < 0.0001) in the agomelatine group. The efficacy of agomelatine for treating PSD is probably comparable to that of SSRIs/SNRIs, and it may improve stroke outcomes with better safety.

Enhanced angiogenesis in the thalamus induced by a novel TSPO ligand ameliorates cognitive deficits after focal cortical infarction.

Neuronal loss in the ipsilateral thalamus after focal cortical infarction participates in post-stroke cognitive deficits, and enhanced angiogenesis in the thalamus is expected to reduce neuronal damage. We hypothesize that novel translocator protein (TSPO) ligand, 2-Cl-MGV-1, can promote angiogenesis, attenuate neuronal loss in the thalamus, and ameliorate post-stroke cognitive deficits. Cortical infarction was induced by distal middle cerebral artery occlusion (dMCAO) in stroke-prone renovascular hypertensive rats. 2-Cl-MGV-1 or dimethyl sulfoxide was administered 24 h after dMCAO and then for 6 or 13 days. Spatial learning and memory were assessed using the Morris water maze. Neuronal loss, TSPO expression, angiogenesis, and intrinsic pathway were determined by immunofluorescence and immunoblotting 7 and 14 days after dMCAO. Cortical infarction caused post-stroke cognitive deficits and secondary neuronal loss with gliosis in the ipsilateral thalamus within 14 days of dMCAO. Increased angiogenesis and elevated expression of vascular TSPO were detected in the ipsilateral thalamus, and treatment with 2-Cl-MGV-1 enhanced angiogenesis by stimulating the PI3K-AKT-mTOR pathway. The effects of 2-Cl-MGV-1 on angiogenesis coincided with reduced neuronal loss in the thalamus and contributed to improvements in post-stroke cognitive deficits. Our findings suggest that 2-Cl-MGV-1 stimulates angiogenesis, ameliorates neuronal loss in the thalamus, and improves post-stroke cognitive deficits.

Effect of radiation therapy on patients with stage T3 or T4 malignant phyllodes tumors: a retrospective observational study based on SEER.

PURPOSE: Among all primary breast tumors, malignant phyllodes tumor of the breast (MPTB) make up less than 1%. In the treatment of phyllode tumors, surgical procedures such as mastectomy and breast-conserving surgery are the mainstay. MPTB has, however, been controversial when it comes to treating it with RT. We aimed to explore the prognostic impact of RT and other clinicopathologic factors on long-term survival for patients with stage T3 or T4 malignant phyllodes tumors. METHODS: We select patients with stage T3 or T4 MPTB who qualified for the criteria between 2000 and 2018 via the Surveillance, Epidemiology, and End Results (SEER) database. We performed 1:1 propensity score matching (PSM) and Kaplan-Meier analysis to explore the role of RT in long-term survival of patients with stage T3 or T4 MPTB. A univariate and multivariate analysis of breast cancer-specific survival (BCSS) and overall survival (OS) risk factors was carried out using a Cox proportional hazards model. In addition, the nomogram graph of OS and BCSS was constructed. RESULTS: A total of 583 patients with stage T3 or T4 malignant phyllodes tumors were included in this study, of whom 154 (26.4%) received RT, and 429 (73.6%) were treated without RT. Before adjustment, between groups with and without RT, BCSS (p = 0.1) and OS (p = 0.212) indicated no significant difference respectively. Using of PSM, the two groups still did not differ significantly in BCSS (p = 0.552) and OS (p = 0.172). In multivariate analysis, age (p < 0.001), surgery of primary site (p < 0.001) and distant metastatic status (p < 0.001) were related to prognosis, while RT still did not affect BCSS (p = 0.877) and OS (p = 0.554). CONCLUSION: Based on the SEER database analysis, the study suggests that the patients with stage T3 or T4 MPTB treated with RT after surgery didn't have significant differences in BCSS or OS compared to those not treated with RT.

Risk Factors and Prognostic Implications of New-Onset Paroxysmal Atrial Fibrillation in Patients Hospitalized with Intracerebral Hemorrhage.

Objective: We aimed to assess the prevalence and risk factors of new-onset paroxysmal atrial fibrillation (PAF) in patients hospitalized with ICH and determine whether the new-onset PAF had influenced functional outcomes. Methods: We analyzed a database of all consecutive patients with ICH from October 2013 to May 2022. Univariate and multivariable regression analyses were performed to identify risk factors for new-onset PAF in patients with ICH. Multivariate models were also constructed to assess whether the new-onset PAF was an independent predictor of poor functional outcome, as measured using the modified Rankin scale. Results: This study included 650 patients with ICH, among whom 24 patients had new-onset PAF. In the multivariable model, older age (OR per 10-y increase, 2.26 [95% CI, 1.52-3.35]; P<0.001), hematoma volume (OR per 10-mL increase, 1.80 [95% CI, 1.26-2.57]; P=0.001), and heart failure (OR, 21.77 [95% CI, 5.52-85.91]; P<0.001) were independent risk factors for new-onset PAF. In a sensitivity analysis restricted to 428 patients with N-terminal pro-B-type natriuretic peptide (NT-proBNP), older age, larger hematoma volume, heart failure, and increased NT-proBNP were associated with new-onset PAF. After adjusting for baseline variables, new-onset PAF was an independent predictor of poor functional outcome (OR, 10.35 [95% CI, 1.08-98.80]; P=0.042). Conclusion: Older age, larger hematoma volume, and heart failure were independent risk factors for new-onset PAF after ICH. Increased NT-proBNP is correlated with higher risks for new-onset PAF when their information is available at admission. Furthermore, new-onset PAF is a significant predictor of poor functional outcome.

Network Pharmacology Prediction and Experimental Verification for Anti-Ferroptosis of Edaravone After Experimental Intracerebral Hemorrhage.

Neuronal ferroptosis plays an important role in secondary brain injuries after intracerebral hemorrhage (ICH). Edaravone (Eda) is a promising free radical scavenger that inhibits ferroptosis in neurological diseases. However, its protective effects and underlying mechanisms in ameliorating post-ICH ferroptosis remain unclear. We employed a network pharmacology approach to determine the core targets of Eda against ICH. Forty-two rats were subjected to successful striatal autologous whole blood injection (n=28) or sham operation (n=14). The 28 blood-injected rats were randomly assigned to either the Eda or vehicle group (n=14) for immediate administration and then for 3 consecutive days. Hemin-induced HT22 cells were used for in vitro studies. The effects of Eda in ICH on ferroptosis and the MEK/ERK pathway were investigated in vivo and in vitro. Network pharmacology-based analysis revealed that candidate targets of Eda-treated ICH might be related to ferroptosis; among which prostaglandin G/H synthase 2 (PTGS2) was a ferroptosis marker. In vivo experiments showed that Eda alleviated sensorimotor deficits and decreased PTGS2 expression (all p<0.05) after ICH. Eda rescued neuron pathological changes after ICH (increased NeuN+ cells and decreased FJC+ cells, all p<0.01). In vitro experiments showed that Eda reduced intracellular reactive oxygen species and reversed mitochondria damage. Eda repressed ferroptosis by decreasing malondialdehyde and iron deposition and by influencing ferroptosis-related protein expression (all p<0.05) in ICH rats and hemin-induced HT22 cells. Mechanically, Eda significantly suppressed phosphorylated-MEK and phosphorylated-ERK1/2 expression. These results indicate that Eda has protective effects on ICH injury through ferroptosis and MEK/ERK pathway suppression.

Supplementary motor area driving changes of structural brain network in blepharospasm.

Blepharospasm is traditionally thought to be a movement disorder that results from basal ganglia dysfunction. Recently, accumulating morphometric studies have revealed structural alterations outside the basal ganglia, such as in the brainstem, cerebellum and sensorimotor cortex, suggesting that blepharospasm may result from network disorders. However, the temporal and causal relationships between structural alterations and whether there are disease duration-related hierarchical structural changes in these patients remain largely unknown. Structural MRI was performed in 62 patients with blepharospasm, 62 patients with hemifacial spasm and 62 healthy controls to assess the structural alterations using voxel-based morphology and structural covariance networks. The use of the causal structural covariance network, modularity analysis and functional decoding were subsequently performed to map the causal effect of grey matter change pattern, hierarchical topography and functional characterizations of the structural network throughout the disease duration of blepharospasm. Greater grey matter volume in the left and right supplementary motor areas was identified in patients with blepharospasm compared to that in patients with hemifacial spasm and healthy controls, whereas no significant difference was identified between patients with hemifacial spasm and healthy controls. In addition, increased grey matter volume covariance between the right supplementary motor area and right brainstem, left superior frontal gyrus, left supplementary motor area and left paracentral gyrus was found in patients with blepharospasm compared to healthy controls. Further causal structural covariance network, modularity analysis and functional decoding showed that the right supplementary motor area served as a driving core in patients with blepharospasm, extending greater grey matter volume to areas in the cortico-basal ganglia-brainstem motor pathway and cortical regions in the vision-motor integration pathway. Taken together, our results suggest that the right supplementary motor area is an early and important pathologically impaired region in patients with blepharospasm. With a longer duration of blepharospasm, increased grey matter volume extends from the right supplementary motor area to the cortico-basal ganglia motor and visual-motor integration pathways, showing a hierarchy of structural abnormalities in the disease progression of blepharospasm, which provides novel evidence to support the notion that blepharospasm may arise from network disorders and is associated with a wide range of grey matter abnormalities.

Mental health and quality of life in patients with craniofacial movement disorders: A cross-sectional study.

Background: Facial appearance and expressions influence social interaction. Hemifacial spasm (HFS), blepharospasm (BPS), and blepharospasm-oromandibular dystonia (BOD) are common forms of craniofacial movement disorders. Few studies have focused on the mental burden and quality of life (QoL) in patients with craniofacial movement disorders. Therefore, this study investigated mental health and QoL in these patients. Methods: This cross-sectional study included 90 patients with craniofacial movement disorders (HFS, BPS, and BOD; 30 patients per group) and 30 healthy individuals without craniofacial movement disorders (control group) recruited from October 2019 to November 2020. All participants underwent QoL and mental health evaluations for depression, anxiety, and stigma using the 36-item Short Form Health Survey (SF-36), Hamilton Anxiety Rating Scale (HAMA), Hamilton Rating Scale for Depression-24 (HAMD-24) and a questionnaire related to stigma. Results: Depression was diagnosed in 37 (41.11%) patients, whereas 30 patients (33.33%) had anxiety. HAMA scores were significantly higher in the BPS and BOD groups than in the control group. Nineteen patients (21.11%) experienced stigma and SF-36 scores were lower in various dimensions in the movement disorders groups compared to healthy controls. The role-physical and social function scores were significantly lower in the movement disorders groups than in the control group all p < 0.05. The vitality scores of the BPS group and mental health scores of the BPS and BOD groups were significantly lower than those of the control group. Correlation analysis showed that the eight dimensions of SF-36 correlated with education level, disease duration, HAMD score, and HAMA score (all p < 0.05). Regression analysis demonstrated that the HAMD score correlated with general health, vitality, social function, role-emotional, and mental health (all p < 0.05). The HAMA score correlated with body pain after adjusting for education level and disease duration. Conclusion: This study highlights the significant frequency of mental symptoms, including depression, anxiety, and stigma, which lower QoL in patients with craniofacial movement disorders.

Remote cortical atrophy and language outcomes after chronic left subcortical stroke with aphasia.

Objective: Subcortical stroke can cause a variety of language deficits. However, the neural mechanisms underlying subcortical aphasia after stroke remain incompletely elucidated. We aimed to determine the effects of distant cortical structures on aphasia outcomes and examine the correlation of cortical thickness measures with connecting tracts integrity after chronic left subcortical stroke. Methods: Thirty-two patients and 30 healthy control subjects underwent MRI scanning and language assessment with the Western Aphasia Battery-Revised (WAB-R) subtests. Among patients, the cortical thickness in brain regions that related to language performance were assessed by the FreeSurfer software. Fiber tracts connecting the identified cortical regions to stroke lesions were reconstructed to determine its correlations with the cortical thickness measures across individual patient. Results: Cortical thickness in different parts of the left fronto-temporo-parietal (FTP) regions were positively related to auditory-verbal comprehension, spontaneous speech and naming/word finding abilities when controlling for key demographic variables and lesion size. Cortical thickness decline in the identified cortical regions was positively correlated with integrity loss of fiber tracts connected to stroke lesions. Additionally, no significant difference in cortical thickness was found across the left hemisphere between the subgroup of patients with hypoperfusion (HP) and those without HP at stroke onset. Conclusions: These findings suggest that remote cortical atrophy independently predicts language outcomes in patients with chronic left subcortical stroke and aphasia and that cortical thinning in these regions might relate to integrity loss of fiber tracts connected to stroke lesions.

Silent brain infarction is associated with carotid siphon calcification in ischemic stroke patients.

BACKGROUND: Silent brain infarction (SBI) had a higher prevalence in ischemic stroke patients than healthy population. Intracranial artery calcification, as the important component of atherosclerosis, is a known risk factor of ischemic stroke. Whether it is also the risk factor of SBI is uncertain. We aimed to assess the association between SBI and carotid siphon calcification (CSC) in ischemic stroke patients. METHODS: We retrospectively collected consecutive data of acute ischemic stroke patients with and without SBI by Magnetic Resonance Imaging (MRI) and calcification using non-contrast Computerized Tomography (NCCT). We used a histopathologically validated method to score the circularity, thickness, and morphology of calcification. Clinical characteristics, prevalence and pattern (intimal and medial) of CSC were compared between patients with and without SBI. The association of CSC and SBI was investigated by logistic regression analysis. RESULTS: Totally, 303 acute ischemic stroke patients were enrolled, of whom 260 (85.8%) had CSC. Patients with SBI were older (64.5 ± 10.4 years vs. 61.3 ± 12.1 years, P = 0.032), had a higher proportion of hypertension (77.5% vs. 65.7%, P = 0.035). Of the 260 CSC patients, there's no significant difference except for hyperlipidemia between patients with SBI and without SBI. The prevalence of intimal pattern of CSC was higher in those with SBI (adjusted odds ratio 2.42, 95% CI 1.219-4.794). CONCLUSIONS: Patients with SBI at acute phase of ischemic stroke have more risk factors than mentioned previously. SBI associated with the intimal pattern of CSC which relate to the atherosclerosis process in symptomatic ischemic stroke patients.

High on-treatment platelet reactivity is associated with poor outcomes after ischemic stroke: A meta-analysis.

OBJECTIVES: High on-treatment platelet reactivity (HTPR) determined by platelet function assays is present in certain patients with ischemic stroke or transient ischemic attack (TIA). However, it is unclear whether HTPR is associated with poor clinical outcomes. Our study aimed to investigate the relationship of HTPR with recurrent vascular events in ischemic stroke or TIA. METHODS: Pubmed (MEDLINE), EMBASE, and Cochrane Library were searched for eligible studies from inception to January 1, 2022. Stata 17.0 software was used to calculate the risk ratio (RR). Subgroup and sensitivity analyses were conducted to assess the source of heterogeneity. A random-effects model was used when heterogeneity was present. Primary endpoint of the meta-analysis was the risk ratio of recurrent vascular events in HTPR Patients. While stroke and TIA, all-cause death, early neurological deterioration, early new ischemic lesions, and stroke severity measured by National Institute of Health Stroke Scale (NIHSS) scores at admission were also pooled. RESULTS: Thirty articles (7995 patients) were eligible including 28 cohort studies and 2 prospective case-control studies. The prevalence of HTPR varied from 5.9% to 60%. HTPR was associated with an increased risk of recurrent vascular events (RR = 2.94, 95% CI 2.04-4.23), stroke recurrence (RR = 2.05; 95% CI 1.43-2.95), and all-cause mortality (RR = 2.43; 95% CI 1.83-3.22). Subgroup analysis showed that HTPR determined by optical aggregometry, Verify-Now system and 11dh TXB2 is related to a higher risk of recurrent vascular events (RR = 3.53, 95% CI 1.51-9.40; RR = 2.16, 95% CI 1.02-4.56; RR = 3.76, 95% CI 1.51-9.40, respectively). Moreover, patients with HTPR had an increased incidence of early neurological deterioration (RR = 2.75; 95% CI 1.76-4.30) and higher NIHSS scores at admission (Mean difference 0.19, 95% CI 0.01-0.36). CONCLUSIONS: This meta-analysis demonstrates HTPR is associated with higher risk of recurrent vascular events, early neurological deterioration and increased severity in patients with ischemic stroke and TIA. HTPR measured by platelet function assays may guide the use of antiplatelet agents in ischemic stroke and TIA.

Altered excitability of motor neuron pathways after stroke: more than upper motor neuron impairments.

BACKGROUND: Previous studies have suggested that impairment occurs in the lower motor neuron (LMN) pathway after stroke, but more research remains to be supported. OBJECTIVE: In this study, we tested the hypotheses: (1) both motor cortex and peripheral nerve pathways have decreased excitability and structural damage after stroke; (2) parameters of transcranial magnetic stimulation motor evoked potentials (TMS-MEP) can be used as predictors of motor function and stroke prognosis. METHODS: We studied five male cynomolgus monkeys with ischaemic stroke. TMS-MEP, cranial MRI, behavioural assessment, neurological scales and pathology were applied. RESULTS: Elevated resting motor threshold (RMT) (p<0.05), decreased TMS-MEP amplitudes (p<0.05) and negative RMT lateralisation were detected in both the affected motor cortex (AMC) and the paretic side median nerve (PMN) at 2 weeks poststroke. Disturbed structure and loose arrangement of myelin sheaths were observed in the PMN through H&E staining and LFB staining at 12 weeks poststroke. The primate Rankin Scale (used for assess the stroke prognosis) scores at 2-12 weeks after middle cerebral artery occlusion were [1, (1; 3)], [1, (1;2)], [1, (1; 1.5)] and [1, (1; 1.5)], respectively. The RMT and RMT lateralisation (AMC) were predictors of stroke prognosis, and the RMT lateralisation of PMN and latency of AMC were predictors of motor impairment. CONCLUSIONS: Both upper motor neuron (UMN) and LMN pathway excitability is reduced after stroke, and structural damage in median nerve 12 weeks after stroke occur. In addition, RMT and RMT lateralisation are predictors of stroke prognosis and motor impairment.