BackgroundNeutrophil extracellular traps (NETs) can induce cellular and tissue damage through inflammatory responses. While the involvement of NETs in psychiatric disorders has shown preliminary potential, a systematic exploration of their link with major depressive disorder (MDD) is imperative. This study evaluated the clinical potential of three NET markers—myeloperoxidase (MPO)-DNA, neutrophil elastase (NE)-DNA, and citrullinated histones (citH3)—for diagnosing MDD and predicting treatment response.MethodsTwo independent clinical cohorts (Cohort 1: n=83; Cohort 2: n=60) and a chronic unpredictable mild stress (CUMS) mouse model were used. Physiotherapy and pharmacotherapy were administered to the two cohorts, respectively. NET markers were measured in plasma samples. Levels of NETs in the hippocampus were detected in CUMS mice. Pharmacological blockade of NET formation was performed in mice.Results(1) Independently validated across two cohorts, plasma levels of NET markers were significantly higher in MDD patients than in healthy participants. (2) In MDD patients, plasma NET markers significantly correlated with neuropsychological assessment scores, serum levels of inflammatory indices, and abnormal activation of the right calcarine and cuneus. (3) Relationship between NETs and C-reactive protein has an significant effect on depressive symptoms. (4) These NET markers could predict changes in 24-item Hamilton Depression Rating Scale scores after antidepressive treatments. (5) Compared with controls, CUMS mice exhibited significantly elevated levels of NE and MPO in the hippocampus. Preventing NET formation significantly reduced NE and MPO levels in plasma and hippocampus, and alleviated depressive-like behavior in CUMS mice.ConclusionsPlasma NETs may be associated with the occurrence and progression of MDD, potentially via inflammatory mechanisms. Plasma NET markers may be used as valuable biomarkers to diagnose MDD and predict patient response to antidepressive treatment. Targeting NET formation could represent a potential therapeutic strategy for depression.

IMPORTANCE:Per preliminary studies, Shengdi Dahuang Decoction (SDD) is potentially effective for acute intracerebral haemorrhage (ICH); however, its effectiveness has not been rigorously assessed in extensive randomised clinical trials. OBJECTIVE:To evaluate whether SDD can improve 90-day functional outcomes in patients with ICH. DESIGN:Randomised, double-blind, placebo-controlled clinical trial included patients with acute ICH within 4 hours of symptom onset at five hospitals in Shanghai, China. INTERVENTIONS:Patients were randomised 1:1 to receive either SDD granules (each sachet contained 15 g of raw Rehmannia glutinosa and 5 g of raw rhubarb) or placebo granules orally or via a nasogastric tube (as soon as possible within 12 hours of onset, two times daily for 7 days), in addition to ICH guideline-directed treatments. Per our preclinical study, SDD reduces inflammatory injury after ICH in rats. MAIN OUTCOMES:The primary outcome measure was the proportion of patients with a score ranging 0-1 on the modified Rankin Scale (mRS) on the 90th day. RESULTS:Of the total 1211 participants with cerebral haemorrhage assessed for eligibility, 483 were enrolled. Of this, 242 participants were randomly assigned to receive SDD granules and 241 to receive placebo granules (mean age, 62.7 years; 72.9% male). Among these, 112 (46.3%) and 84 (34.9%) patients in the SDD and placebo groups, respectively, had an mRS score of 0-1 on the 90th day (adjusted relative risk 1.20, 95% CI 1.00 to 1.43; p=0.046) . The proportion of patients with poor clinical outcomes (mRS score of 5 or 6 at 90 days) was higher in the placebo group (11.2%) than in the SDD group (5.4%) (p=0.021). The 90-day mortality rate (p=0.299), 7-day National Institute of Health Stroke Scale score (p=0.583), 7-day Glasgow Coma Scale score (p=0.577), 24-hour haematoma enlargement rate (p=0.675) or 7-day relative perihaematomal oedema did not significantly differ (p=0.343) between the groups. The incidence of adverse events between the two groups did not differ significantly (p>0.05). CONCLUSIONS:In patients with acute ICH, incorporating SDD as a supplementary intervention alongside guideline-directed treatments may help enhance 90-day functional outcomes; however, more clinical trials are required to further prove its efficacy. TRIAL REGISTRATION NUMBER:NCT04200781.

To investigate potential associations between cerebrospinal fluid (CSF) microplastics and Alzheimer's disease (AD) pathology or cognitive function. The study included two cohorts: Cohort 1 comprised 17 amyloid-positive and 15 amyloid-negative subjects, while Cohort 2 consisted of 11 amyloid-positive subjects. All amyloid-positive participants in Cohort 1 completed one-year follow-up. CSF amyloid-β(Aβ)42, Aβ40, p-tau181, and t-tau were measured. Amyloid status defined by CSF Aβ42/40 ratio (positive: < 0.1; negative: ≥ 0.1). Four types of microplastics, namely polypropylene, polyvinyl chloride (PVC), polyethylene (PE), and polystyrene, were detected in human CSF. Bottled water consumption frequency and CSF/serum albumin ratio significantly correlated with CSF microplastic abundance. In Cohort 1, amyloid-positive subjects exhibited significantly elevated CSF levels of PE and PVC as compared to amyloid-negative subjects. In amyloid-positive subjects (Cohort 1 and 2), CSF PE levels showed significant inverse correlations with both CSF Aβ42 levels and Mini-Mental State Examination (MMSE) scores. In amyloid-positive individuals of Cohort 1, elevated PE levels positively correlated with MMSE decline rate over one year. The levels of CSF Aβ42 served as an intermediary factor, significantly affecting the relationship between CSF PE and MMSE scores in amyloid-positive subjects of cohort 1. In Cohort 1, the CSF levels of PE and PVC demonstrated an area under the curve value of greater than 0.8, indicating their strong potential to differentiate between amyloid-positive and amyloid-negative individuals. These discoveries suggested that the gradual accumulation of microplastics in the CSF were associated with cognitive decline among AD individuals.

Hearing loss caused by stroke must be taken seriously, as it is a treatable condition that highly depends on timely intervention. This case report presents a rare case of a 75-year-old female with a history of hypertension who visited the Emergency Department of Otolaryngology due to sudden left-sided deafness accompanied by vertigo and vomiting, and magnetic resonance imaging (MRI) demonstrated acute posterior circulation cerebral infarction.In the Emergency Department setting, for middle-aged and elderly patients with vascular risk factors, hearing loss may serve as an early warning sign of vertebrobasilar artery ischemic stroke. Immediate stroke screening should always be prioritized, as acute antithrombotic and acute revascularization treatments may be necessary.

BackgroundThe current study aimed to explore the specific oral microbiota profiles in major depressive disorder (MDD) patients with sleep disturbances, and to evaluate the potential mechanisms by which oral microbiota may be implicated in MDD.MethodThirty-eight MDD patients experiencing sleep disturbances and thirty healthy controls (HCs) were included. All MDD patients underwent a 14-day antidepressive treatment regimen. Neuropsychological assessments were conducted, and 16S rRNA sequencing was used to determine the abundance of oral bacteria.ResultsOral genera Solobacterium, Granulicatella, Campylobacter, and Haemophilus showed significant changes in their relative abundances between the MDD and HC groups. Significant correlations were found between the abundance of Haemophilus and Pittsburgh Sleep Quality Index (PSQI) and 24-item Hamilton Depression Scale (HAMD-24) scores in MDD patients with sleep disturbances. In MDD patients, lower relative abundances of oral Haemophilus prior to treatment were negatively correlated with the changed rates of PSQI and HAMD-24 scores after antidepressive treatment. The glial fibrillary acidic protein as the mediator, affected the relationship between the relative abundance of oral Haemophilus and sleep disturbances in MDD patients.ConclusionOral Haemophilus dysbiosis may drive sleep disturbances in MDD patients, possibly through its impact on neuroinflammation.

AIMS:Ischemic stroke (IS), a major global health concern, is associated with aging-related clonal hematopoiesis of indeterminate potential (CHIP), though their mechanistic connection remains unclear. This study explores the causal CHIP-IS relationship, key genetic drivers, and potential therapies. METHODS:Genetic markers for CHIP were selected as instrumental variables and analyzed through bidirectional two-sample Mendelian randomization (MR) using GWAS data from IS cohorts. Functional annotation of significant loci was performed via FUMA, while transcriptomic datasets from GEO underwent differential expression analysis, weighted gene co-expression network construction, and machine learning-driven biomarker discovery. Protein-protein interaction networks and single-cell RNA sequencing (scRNA-seq) were employed to elucidate cellular mechanisms. RESULTS:MR analysis revealed a significant causal association between CHIP and cardioembolic stroke (CES) risk (OR = 70.15, 95% CI = 2.03-2428.52, p = 0.02). PARP1 and CD3G emerged as hub genes connecting CHIP to IS pathogenesis, validated through multi-omics integration. Fourteen feature genes were identified, and potential therapeutic drugs targeting this pathway were discovered. scRNA-seq analysis further demonstrated downregulation of CD3G in T cells post-IS, disrupting immune cell communication and differentiation. CONCLUSION:This study provides robust genetic evidence for CHIP-mediated predisposition to CES and identifies PARP1 and CD3G as critical therapeutic targets. The integration of machine learning and single-cell genomics offers novel insights into immune dysregulation in IS, paving the way for precision prevention strategies in CHIP patients.

Research on the gut-brain-immune axis shows it plays a critical role in ischemic stroke, but the exact causal links between gut bacteria imbalance, immune system problems, and brain blood vessel damage remain unclear. To investigate this, we combined multiple types of biological data using a statistical method called Bayesian weighted Mendelian randomization (BWMR). We analyzed large genetic datasets covering 731 immune cell traits, 91 inflammatory proteins, 412 gut microbes and their pathways, and ischemic stroke cases. Shared genetic variants were confirmed using colocalization, and we used computer simulations to explore potential treatments. The analysis found that genetically predicted higher levels of the protein CD27 on specific memory B cells (CD24+ CD27+ and IgD- CD38dim) directly increased the risk of stroke caused by large-artery atherosclerosis. Computer modeling indicated that a compound called Dioscin could potentially block CD27 effectively. Conversely, bacteria from the order Burkholderiales (specifically at the family, genus, and species level Burkholderiales_bacterium_1_1_47) showed strong protective effects against small-vessel stroke. Further analysis revealed that about 12.6% of the protective effect of the gut bacterium g_Odoribacter worked through the signaling protein FGF19. This study identifies CD27-positive B cells as key drivers of brain inflammation in stroke and suggests Dioscin as a promising treatment candidate. It also demonstrates a protective mechanism where specific gut microbes communicate with blood vessels in the brain via FGF19, providing a foundation for new stroke therapies targeting the microbiome and immune system.

OBJECTIVE:Altered cerebral perfusion has been implicated in the development of white matter hyperintensities (WMHs), yet the specific influence of hemodynamic features in proximal arteries on WMH burden remains uncertain. This study aimed to investigate the relationship between arterial flow characteristics and WMH severity. METHODS:A total of 2631 subjects (68.6 ± 11.1 years, 50.3% female) who underwent MRI (magnetic resonance imaging) and MRA (magnetic resonance angiography) scans were involved in this retrospective observational study. Using an individualized simplified hemodynamic model, we derived arterial flow rate, mean pressure, and pressure drop for each MRA-visible branch. WMHs were quantified on T2-FLAIR images and categorized into periventricular and deep subtypes. The associations between arterial features and WMH burden were examined using general linear models. RESULTS:Higher mean flow rate (β = 0.10, 95% CI: 0.06-0.14, p < 0.001) and mean pressure (β = 0.03, 95% CI: 0.02-0.04, p < 0.001) were associated with increased WMH volume. Adjacent-to-lesion terminal arterial branches (ALTAB), which represented arteries surrounding WMH, exhibited greater length (21.7 ± 8.21 mm vs. 13.3 ± 2.35 mm, p < 0.001), greater tortuosity (1.52 ± 0.39 vs. 1.26 ± 0.11, p < 0.001), lower mean flow rates (0.40 ± 0.09 mL/min vs. 0.90 ± 0.25 mL/min, p < 0.001) and lower pressure drops (0.42 ± 0.16 mmHg vs. 0.54 ± 0.15 mmHg, p < 0.001) compared to distant arteries. Greater WMH volume was found to be associated with an increased number of ALTAB. CONCLUSION:The hemodynamic features of arteries surrounding WMH exhibited significant differences compared to those located further away. Such changes in arterial morphology and corresponding hemodynamic features might be associated with the severity of WMH.

Growing evidence has suggested that elevated Trimethylamine N-oxide (TMAO) levels, a gut microbiota-dependent metabolite, are closely associated with brain aging and cognitive impairment. Glycogen synthase kinase-3 beta (GSK-3β) activity was depicted to be essential in regulating learning and memory. The current study examined the impact of TMAO on cognitive function in mild cognitive impairment (MCI) patients and rat models while exploring the mechanisms regulating the TMAO-induced GSK-3β signaling. This study recruited 115 MCI patients and 128 healthy controls. All participants underwent neuropsychological assessments. Fasting plasma TMAO was measured using high-performance liquid chromatography with online electrospray ionization tandem mass spectrometry. The study also explored whether the GSK-3β signaling was involved in cognitive and function deficits linked with elevated TMAO in rat models. Our results indicated that TMAO plasma levels were elevated in MCI patients compared to healthy controls, depicting a significant association with potential MCI risk. Furthermore, chronic exposure to choline considerably impacted spatial cognitive performance in the Morris water maze task. This reduced the phosphorylation of Ser9 of GSK-3β and the synaptic plasticity-related proteins within the hippocampus, which could be restored by inhibiting TMAO with ABS. In addition, inhibition of GSK-3β by SB216763 significantly prevented the TMAO-induced synaptic damage while decreasing the membrane level of GluA1 and improving hippocampal learning and memory. These results indicate that TMAO can induce hippocampal-dependent learning and memory ability impairment with deficits in synaptic plasticity by regulating the GSK-3β activity.

Little is known about how thalamic vascular patterns interact with small vessel diseases (SVDs) to influence affective symptoms. Here we collected 7-Telsa magnetic resonance imaging (MRI) data from 84 individuals with SVD and analyzed the influences of thalamic vascular pattern on affective symptoms, aiming to elucidate the underlying mechanisms driven by brain structure and function in the context of SVD. Subjects with a combined arterial supply by tuberothalamic and paramedian arteries to the right thalamus exhibited a lower Hamilton Anxiety scale (HAMA) score. When grouped by SVD burden, the same correlation remained in subjects with low SVD burden, whereas no difference was observed in the high SVD burden group. Interestingly, interaction effects of SVD and thalamic vascular pattern were also found affecting thalamic volume and resting-state brain activity in ventromedial prefrontal cortex (vmPFC). With moderated mediation analysis, right thalamic vascular pattern was indicated to affect anxiety through both direct (vascular pattern → HAMA score) and indirect (vascular pattern → thalamic volume → HAMA score) pathways. But high SVD burden interrupted the effects of right thalamic vascular pattern on HAMA score and thalamic volume. The finding that subjects with a combined arterial supply to the right thalamus exhibited a lower level of anxiety may suggest a novel vascular resilience for regulating anxiety. However, this vascular compensation mechanism was found to be impaired by elevated SVD burden and the disrupted inhibitory vmPFC activity caused by impaired thalamus. The findings of the present study provide a new underlying mechanism for affective disorders with SVD involved.

BackgroundThis study aimed to establish an intelligent segmentation algorithm to count the number of deep medullary veins (DMVs) and analyze the relationship between DMVs and imaging markers of cerebral small vessel disease (CSVD).MethodsDMVs on magnetic resonance imaging (MRI) of patients with CSVD were counted by intelligent segmentation and manual counting. The dice coefficient and intraclass correlation coefficient (ICC) were used to evaluate their consistency and correlation. Structural MR images were used to assess imaging markers and total burden of CSVD. A multivariate linear regression model was used to evaluate the correlation between the number of DMVs counted by intelligent segmentation and imaging markers of CSVD, including white matter hyperintensities of the presumed vascular origin, lacune, perivascular spaces, cerebral microbleeds, and total CSVD burden.ResultsA total of 305 patients with CSVD were enrolled. An intelligent segmentation algorithm was established to calculate the number of DMVs, and it was validated and tested. The number of DMVs counted intelligently significantly correlated with the manual counting method (r=0.761, P<0.001). The number of smart-counted DMVs negatively correlated with the imaging markers and total burden of CSVD (P<0.001), and the correlation remained after adjusting for age and hypertension (P<0.05).ConclusionsThe proposed intelligent segmentation algorithm, which was established to count DMVs, can provide objective and quantitative imaging information for the follow-up of patients with CSVD. DMVs are involved in CSVD pathogenesis and a likely new imaging marker for CSVD.

Ethnopharmacological relevance: Huzhangqingmaiyin (HZQMY) is a Chinese medicine formula used to treat small vessel disease, but the mechanism is unclear.Aim of the study: This study aimed to reveal the protective effects of HZQMY on human brain microvascular endothelial cells (HBMECs) and explore the potential targets and mechanistic pathways using network pharmacology on treating cerebral small vessel disease (CSVD).Materials and methods: HBMECs were cultured in vitro and an endothelial cell injury model was constructed by hypoxia for 12 h followed by reoxygenation for 8 h (H/R). Cell viability was measured by CCK-8 assay, migration ability of cells was detected by scratch assay, angiogenesis ability of endothelial cells was detected by tubulogenesis assay. Meanwhile, JC-1 staining was employed to determine the alteration of mitochondrial membrane potential, and finally, cell apoptosis was assessed by flow cytometry. To further explore the mechanism of action of HZQMY, the target proteins of a candidate active compound was first collected from the traditional Chinese medicine systems pharmacology database with analytical platform and Swiss target prediction database (www. swisstargetprediction.ch) by HPLC/MS determination of its main active components. CSVD associated targets were retrieved from four disease associated targets databases, OMIM, DisGenNET, GeneCards and GeneCLip, respectively. Using the website String, the genes overlapped between HZQMY and CSVD were imported into the database, PPI network plots were drawn using Cytoscape software. GO and KEGG analyses were performed to explore the possible pathways and targets of HZQMY. Its most probable targets were further explored with molecular docking and verified.Results: HZQMY at 0.5-2 & mu;g/mL concentration range could promote cell proliferation, cell migration, angiogenesis, reduce mitochondrial membrane potential damage as well as inhibit apoptosis. Besides that, 29 active compounds were detected from HZQMY, including key components such as quercetin, polydatin, kaempferol, isorhamnetin and resveratrol. Core targets that might include IL-1 & beta;?ICAM-1?VCAM-1 and VEGF and so on. Conclusions: HZQMY could regulate the levels of key targets such as IL-1 & beta;?ICAM-1?VCAM-1 and VEGF, so as to achieve the purpose of treating CSVD.

Gait disturbance is a manifestation of cerebral small vessel disease (CSVD). The posterolateral thalamus (PL), whose blood is mainly supplied by the P2 segment of posterior cerebral artery (P2-PCA), plays pivotal roles in gait regulation. We investigated the influence of the distance between P2-PCA and PL on gait with varying CSVD burden. 71 participants were divided into low and high CSVD burden groups. The distance from P2-PCA to PL was measured using 7 T TOF-MRA and categorized into an immediate or distant PCA-to-thalamus pattern. Functional connectivity (FC) and voxel-based morphometry were assessed to evaluate functional and structural alterations. In the low CSVD burden group, immediate PCA-to-thalamus supply strongly correlates with longer step length and higher wave phase time percent, and exhibited enhanced FCs in left supplementary motor area, right precentral cortex (PreCG.R). While in the high CSVD burden group, no association between PCA-to-thalamus pattern and gait was found, and we observed reduced FC in PreCG.R with immediate PCA-to-thalamus pattern. Higher CSVD burden was associated with decreased gray matter density in bilateral thalamus. However, no significant structural thalamic change was observed between the two types of PCA-to-thalamus patterns in all patients. Our study demonstrated patients with immediate PCA-to-thalamus supply exhibited better gait performance in low CSVD burden populations, which also correlated with enhanced FCs in motor-related cortex, indicating the beneficial effects of the immediate PCA-to-thalamus supply pattern. In the higher burden CSVD populations, the effects of PCA-to-thalamus pattern on gait are void, attributable to the CSVD-related thalamic destruction and impairment of thalamus-related FC.

We describe contrast-enhanced CT and FDG PET/CT findings in a case of thoracic SMARCA4-deficient undifferentiated tumor with extensive pleural involvement and mediastinal lymph node metastases. Contrast-enhanced CT showed multiple enhancing right-sided pleural masses and soft tissue plaques and enlarged mediastinal lymph nodes. The pleural lesions and mediastinal lymph nodes showed intense FDG uptake mimicking malignant pleural mesothelioma with mediastinal lymph node metastases.

Abstract Gardner syndrome is characterized by multiple intestinal polyps and extraintestinal lesions. We describe FDG PET/CT findings of the extraintestinal lesions in a patient with Gardner syndrome. FDG PET/CT showed 2 hypermetabolic desmoid tumors in the abdominal wall, sclerotic areas with multifocal activity in the maxilla and mandible, multiple osteomas in the bilateral parietal, left frontal, sphenoid and ethmoid bones, an impacted tooth in the right maxilla, and bone islands in the T2 and T5 vertebral bodies. Extraintestinal involvements in Gardner syndrome can precede intestinal polyposis. Therefore, familiarity with FDG PET/CT findings of extraintestinal manifestations is helpful for early diagnosis.

Abstract Juxtaglomerular cell tumor or reninoma is an extremely rare, typically benign, renin-secreting tumor of the kidney that causes secondary hypertension. We describe 99mTc-MIBI SPECT/CT findings in a case of juxtaglomerular cell tumor. The renal tumor showed isodensity and photopenia on 99mTc-MIBI SPECT/CT. This case indicates that juxtaglomerular cell tumor can appear cold on 99mTc-MIBI SPECT/CT, mimicking renal cell carcinoma.

As the pathogenesis of cerebral small vessel disease with cognitive impairment (CSVD-CI) remains unclear, identifying effective biomarkers can contribute to the clinical management of CSVD-CI. This study recruited 54 healthy controls (HCs), 60 CSVD-CI patients, and 57 CSVD cognitively normal (CSVD-CN) patients. All participants underwent neuropsychological assessments and multimodal magnetic resonance imaging. Macrophage migration inhibitory factors (MIFs) were assessed in plasma. The least absolute shrinkage and selection operator model was used to determine a composite marker. Compared with HCs or CSVD-CN patients, CSVD-CI patients had significantly increased plasma MIF levels. In CSVD-CI patients, plasma MIF levels were significantly correlated with multiple cognitive assessment scores, plasma levels of blood-brain barrier (BBB)-related indices, white matter hyperintensity Fazekas scores, and the mean amplitude of low-frequency fluctuation in the right superior temporal gyrus. Higher plasma MIF levels were significantly associated with worse global cognition and information processing speed in CSVD-CI patients. The composite marker (including plasma MIF) distinguished CSVD-CI patients from CSVD-CN and HCs with >80% accuracy. Meta-analysis indicated that blood MIF levels were significantly increased in CSVD-CI patients. In conclusion, plasma MIF is a potential biomarker for early identification of CSVD-CI. Plasma MIF may play a role in cognitive decline in CSVD through BBB dysfunction and changes in white matter hyperintensity and brain activity.

Chronic cerebral hypoperfusion is an important pathological factor in many neurodegenerative diseases, such as cerebral small vessel disease (CSVD). One of the most used animal models for chronic cerebral hypoperfusion is the bilateral common carotid artery stenosis (BCAS) mouse. For the therapy of CSVD and other diseases, it will be beneficial to understand the pathological alterations of the BCAS mouse, particularly vascular pathological changes. A mouse model of BCAS was used, and 8 weeks later, cognitive function of the mice was examined by using novel object recognition test and eight-arm radial maze test. 11.7 T magnetic resonance imaging (MRI) and luxol fast blue staining were used to evaluate the injury of the corpus callosum (CC), anterior commissure (AC), internal capsule (IC), and optic tract (Opt) in the cerebral white matter of mice. Three-dimensional vascular images of the whole brain of mice were acquired using fluorescence micro-optical sectioning tomography (fMOST) with a high resolution of 0.32 × 0.32 × 1.00 μm 3 . Then, the damaged white matter regions were further extracted to analyze the vessel length density, volume fraction, tortuosity, and the number of vessels of different internal diameters. The mouse cerebral caudal rhinal vein was also extracted and analyzed for its branch number and divergent angle in this study. BCAS modeling for 8 weeks resulted in impaired spatial working memory, reduced brain white matter integrity, and myelin degradation in mice, and CC showed the most severe white matter damage. 3D revascularization of the whole mouse brain showed that the number of large vessels was reduced and the number of small vessels was increased in BCAS mice. Further analysis revealed that the vessel length density and volume fraction in the damaged white matter region of BCAS mice were significantly reduced, and the vascular lesions were most noticeable in the CC. At the same time, the number of small vessels in the above white matter regions was significantly reduced, while the number of microvessels was significantly increased in BCAS mice, and the vascular tortuosity was also significantly increased. In addition, the analysis of caudal rhinal vein extraction revealed that the number of branches and the average divergent angle in BCAS mice were significantly reduced. The BCAS modeling for 8 weeks will lead to vascular lesions in whole brain of mice, and the caudal nasal vein was also damaged, while BCAS mice mainly mitigated the damages by increasing microvessels. What is more, the vascular lesions in white matter of mouse brain can cause white matter damage and spatial working memory deficit. These results provide evidence for the vascular pathological alterations caused by chronic hypoperfusion.

This study was designed to evaluate antiplatelet effect and therapeutic effect of ginkgo diterpene lactone meglumine injection (GDLI) in acute ischemic stroke (AIS) patients. In this randomized, double-blind, placebo-controlled trial, we randomly assigned 70 inpatients within 48 hr after the onset of AIS to combination therapy with GDLI and aspirin (GDLI at a dose of 25 mg/d for 14 days plus aspirin at a dose of 100 mg/d for 90 days) or to placebo plus aspirin in a ratio of 1:1. Platelet function, the National Institute of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) were evaluated. A good outcome was defined as NIHSS scores decrease >= 5 or mRS scores decrease >= 2. Results showed that arachidonic acid induced maximum platelet aggregation rate (AA-MAR) and mean platelet volume (MPV) of the GDLI-aspirin group were much lower than that of the aspirin group (p = 0.013 and p = 0.034, respectively) after the 14-day therapy. The combination of GDLI and aspirin was superior to aspirin alone, and had significant impact on the good outcome at day 90 (ORadj 7.21 [95%CI, 1.03-50.68], p = 0.047). In summary, GDLI has antiplatelet effect and can improve the prognosis of AIS patients.

No acceptable biomarker can facilitate the early identification of cognitive impairment associated with cerebral small vessel disease (CSVD) in the older persons. The neutrophil extracellular traps (NETs) in the inflammation response of circulatory and central systems are essential in destroying the blood-brain barrier. The present study aims to explore the potential associations of plasma NETs with cognitive performance in CSVD. We recruited 146 CSVD patients and 66 healthy controls (HCs), and comprehensive neuropsychological assessments and multimodal magnetic resonance imaging were conducted. Three NETs markers, namely citrullination of histone H3, neutrophil elastase-DNA, and myeloperoxidase (MPO)-DNA, and 4 oxidative stress-related indexes in plasma samples, were measured. The plasma levels of 3 NETs markers were more significantly elevated in CSVD patients than in HCs. Significant correlations of the 3 NETs markers were observed with multiple cognitive domain scores. Furthermore, higher plasma malondialdehyde and NETs levels were significantly associated with the worse Montreal Cognitive Assessment scores among CSVD patients. Moreover, plasma MPO-DNA levels significantly mediated the effect of the amplitude of low-frequency fluctuation value within the bilateral caudate and the scores of global cognitive function, executive function, and information processing speed. Additionally, a panel of 3 NETs markers had the highest area under the curve value to distinguish the cognitively impaired CSVD patients from HCs and nonimpaired ones. Therefore, plasma NETs may be potential biomarkers for early diagnosis of CSVD-related cognitive impairment. Activated lipid peroxidation in circulation and impaired caudate function support potential associations of plasma NETs in cognitively impaired CSVD patients.