Ischemic stroke (IS), a cerebrovascular disease, is the leading cause of physical disability and death worldwide. Tissue plasminogen activator (tPA) and thrombectomy are limited by a narrow therapeutic time window. Although strategies such as drug therapies and cellular therapies have been used in preclinical trials, some important issues in clinical translation have not been addressed: low stem cell survival and drug delivery limited by the blood-brain barrier (BBB). Among the therapeutic options currently sought, carrier-based hydrogels hold great promise for the repair and regeneration of neural tissue in the treatment of ischemic stroke. The advantage lies in the ability to deliver drugs and cells to designated parts of the brain in an injectable manner to enhance therapeutic efficacy. Here, this article provides an overview of the use of carrier-based hydrogels in ischemic stroke therapy and focuses on the use of hydrogel scaffolds containing bioactive molecules and stem cells. In addition to this, we provide a more in-depth summary of the composition, physicochemical properties and physiological functions of the materials themselves. Finally, we also outline the prospects and challenges for clinical translation of hydrogel therapy for IS.

Ischemic stroke (IS) is the leading cause of worldwide death while the discovery and effective delivery of neuroprotective agents for satisfied IS treatment is still challenging.

In this study, we discover that celery seed (CS) derived reconstituted lipid nanoparticles (CS-rLNPs) can effectively penetrate across blood-brain barrier (BBB) with increased distribution to the brain. Especially, CS-rLNPs show innate neuron-targeting ability to primarily bind to neuron in the cerebral ischemic area, which is not reported by any parallel studies. Moreover, CS-rLNPs are found to exert therapeutic effects on IS, which effectively restore the function of model mice. Further studies reveal that the therapeutic effects are realized through TLR4/MyD88/NF-κB p65 pathway regulated anti-inflammation and anti-apoptosis mechanisms.

Therefore, CS-rLNPs can serve as a neuron-targeted neuroprotective nanomedicine for IS treatment.

This study aimed to explore the relationship between the systemic immune-inflammatory index (SII) and the probability of in-hospital mortality among acute ischemic stroke (AIS) with atrial fibrillation (AF) patients undergoing intravenous thrombolysis.

This single-center, retrospective observational study included individuals among AIS with AF who received intravenous thrombolysis. The SII is determined by taking the product of the platelet and neutrophil counts, followed by dividing this result by the lymphocyte count. In-hospital mortality was defined as a Modified Rankin Scale (mRS) score of 6 point. The investigation applied logistic regression models, along with subgroup, sensitivity, and receiver operating characteristic (ROC) curve analyses assessments, to explore the relationship between the SII and in-hospital mortality.

541 patients were included in this study, 50 (9.24%) of whom died during their hospital stay. Multifactorial logistic regression analyses using fully adjusted models, demonstrated that the SII is independently associated with the risk of in-hospital death. Patients with elevated SII levels experienced a significantly increased risk of in-hospital mortality, which was found to be 2.557 (95% CI: 1.154-5.665, P = 0.021) times greater compared to those with lower SII levels. Through multivariate logistic regression analyses, a notable correlation between the SII and the probability of death during hospitalization was observed across various subgroups, including individuals aged ≤75 and >75years, women, patients with persistent AF, those receiving thrombolytic therapy, diabetic and nondiabetic patients, individuals with BMI ≥24 kg/m2, and those with an admission National Institutes of Health Stroke Scale score ≤20 (P < 0.05). Two sensitivity analyses confirmed the robustness of this association from multiple perspectives (P < 0.05). ROC analysis demonstrated that the SII, the baseline model, and their combined model all showed strong predictive power for in-hospital mortality. Notably, the combined model outperformed the SII alone (P < 0.05). In addition, the predictive value of SII for in-hospital death was significantly higher than that of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR).

A significant association has been observed between the risk of in-hospital death among AIS with AF individual undergoing intravenous thrombolysis and the SII.

While treatments exist for the acute phase of stroke, there are limited options for patients with chronic infarcts and long-term disability. Allogenic mesenchymal stem cells (alloMSCs) show promise for the treatment of stroke soon after ischemic injury. There is, however, no information on the use of autologous MSCs (autoMSCs), delivered intracerebrally in rats with a chronic infarct. In this study, rats underwent middle cerebral artery occlusion (MCAO) to induce stroke followed by bone marrow aspiration and MSC expansion in a closed bioreactor. Four weeks later, brain MRI was obtained and autoMSCs (1 × 106, 2.5 × 106 or 5 × 106; n = 6 each) were stereotactically injected into the peri-infarct and compared to controls (MCAO only; MCAO + PBS; n = 6-9). Behavior was assessed using the modified neurological severity score (mNSS). For comparison, an additional cohort of MCAO rats were implanted with 2.5 × 106 alloMSCs generated from a healthy rat. All doses of autoMSCs produced significant improvement (54-70%) in sensorimotor function 60 days later. In contrast, alloMSCs improved only 31.7%, similar to that in PBS controls 30%. Quantum dot-labeled auto/alloMSCs were found exclusively at the implantation site throughout the post-transplantation period with no tumor formation on MRI or Ki67 staining of engrafted MSCs. Small differences in stroke volume and no differences in corpus callosum width were observed after MSC treatment. Stroke-induced glial reactivity in the peri-infarct was long-lasting and unabated by auto/alloMSC transplantation. These studies suggest that intracerebral transplantation of autoMSCs as compared to alloMSCs may be a promising treatment in chronic stroke.

The present protocol provides general recommendations based on the best evidence currently available for physiotherapists to use as a guide for the care of stroke patients during hospitalization. The Brazilian Early Stroke Rehabilitation Task Force, comprising physical therapy experts and researchers from different Brazilian states, was organized to develop this care protocol based on a bibliographical survey, including meta-analyses, systematic reviews, clinical trials, and other more recent and relevant scientific publications. Professionals working in stroke units were also included in the task force to ensure the practicality of the protocol in different contexts. This protocol provides guidance on assessment strategies, safety criteria for the mobilization of patients with stroke, recommendations for mobilization and proper positioning, as well as evidence-based practices for treatment during hospitalization, including preventive measures for shoulder pain and shoulder-hand syndrome. The protocol also provides information on the organization of the physiotherapy service at stroke units, guidelines for hospital discharge, and quality indicators for physiotherapy services. We have included detailed activities that can be performed during mobilization in the supplementary material, such as postural control training, sensory and perceptual stimulation, task-oriented training, and activities involving an enriched environment. The protocol was written in a user-friendly format to facilitate its application in different social and cultural contexts, utilizing resources readily available in most clinical settings.

Acute ischemic stroke (AIS) initiates secondary injuries that worsen neurological damage and hinder recovery. While peripheral immune responses play a key role in stroke outcomes, clinical results from immunotherapy have been suboptimal, with limited focus on T-cell dynamics. Umbilical mesenchymal stem cells (UMSCs) offer therapeutic potential due to their immunomodulatory properties. They can regulate immune responses and reduce neuroinflammation, potentially enhancing recovery by fostering a pro-regenerative peripheral immune environment. However, the effect of UMSCs on T-cell dynamics in AIS remains underexplored. This study investigates T-cell dynamics following AIS and examines how UMSCs may mitigate immune dysregulation to develop better treatment strategies.

AIS patients (NIHSS scores 0-15) were recruited within 72 h of stroke onset, with peripheral blood samples collected on Day 0 (enrollment) and Day 7. T-cell compartments were identified by flow cytometry, and plasma cytokine levels were quantified using a cytometric bead array (CBA). Mitochondria in UMSCs were labeled with MitoTracker. Peripheral blood mononuclear cells from patients were isolated, treated with lipopolysaccharide (LPS), and cocultured with UMSCs in both direct contact and Transwell systems. Flow cytometry, CBA, RT-qPCR, and immunofluorescence assays were used to detect T-cell compartments, gene expression markers for helper T (Th) cell differentiation, cytokine profiles, mitochondrial transfer, reactive oxygen species (ROS) production, and mitochondrial membrane potential. Additionally, mitochondrial DNA in UMSCs was depleted. The effects of UMSCs and mitochondria-depleted UMSCs on ischemic stroke mice were compared through behavioral assessments and analysis of the peripheral immune microenvironment.

In AIS, T-cell compartments underwent a phenotypic shift from naïve to effector or memory states, with a specific increase in Th17 cells and a decrease in regulatory T cells, leading to alterations in T-cell-mediated immune functions. In an ex vivo co-culture system, LPS stimulation further amplified these disparities, inducing mitochondrial dysfunction and oxidative stress in T cells. Notably, UMSCs restored mitochondrial function and reversed the shift in T-cell compartments through mitochondrial transfer. Critically, UMSC treatment significantly improved both neurological deficits and peripheral immune disorders in ischemic stroke mice, whereas mitochondria-depleted UMSCs failed to produce this effect.

Our comprehensive insights into the key attributes of T-cell compartments in acute ischemic stroke and the immune regulatory mechanisms of UMSCs provide a crucial theoretical foundation for understanding peripheral immune disorders in ischemic stroke and the therapeutic potential of UMSC treatment.

The acute phase of ischemic stroke is marked by a surge in matrix metalloproteinase-9 (MMP-9) activity. While integral to natural repair processes, MMP-9 exacerbates injury by breaking down the blood-brain barrier (BBB) and promoting edema and inflammation. MMP-9 is predominantly secreted by inflammatory cells such as neutrophils, macrophages and microglia soon after stroke onset. In this study we investigated the effects of MMP-9 inhibition via SB-3CT on astrocytic lipid metabolism, and its potential to enhance neuronal survival and recovery following ischemic stroke. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min, mice then were injected with SB-3CT (25 mg/kg, i.v.). On D3 post tMCAO, neurological outcomes were assessed, and whole brains were collected for analysis. Lipidomic analysis of brain tissue showed that SB-3CT treatment significantly restrained astrocytic cholesterol metabolism by modulating the sphingolipid and glycerophospholipid pathways. Specifically, SB-3CT reduced ceramide accumulation and promoted an increase in neuroprotective hexosylceramides, leading to enhanced neuronal survival and synaptic integrity. In addition, SB-3CT treatment reduced astrocytic and microglial reactivity, thereby mitigating neuroinflammation. In order to optimize the timing and dosage of MMP-9 inhibition to maximize the therapeutic efficacy, tMCAO mice were given three injections of SB-3CT on D0, D2 and D4 within 7 days after modeling. We found that prolonged MMP-9 inhibition alleviated astrogliosis, concurrently impaired neurological recovery and inhibited angiogenesis. These results demonstrate the critical role of lipid metabolism in MMP-9-mediated brain injury and the potential of SB-3CT as a therapeutic strategy for ischemic stroke by targeting astrocytic lipid metabolism.

The purpose of this study is to identify the therapeutic effect of electroacupuncture (EA) on cerebral ischemia-reperfusion (I/R) injury, and to clarify the regulatory mechanism related to telomerase reverse transcriptase (TERT)-mediated telomerase activity. A Middle cerebral artery occlusion/reperfusion (MCAO/R) animal model was constructed and rats were treated by EA invention at the Baihui (GV20) and Fengchi (GB20) acupoints. Neurological deficits were assessed via rotarod test and Morris water maze test. 2,3,5-Triphenyltertrazolium chloride (TTC) staining was performed to evaluate infarct volume. Histological changes were observed under H&E staining and Nissl staining. TERT expression was examined using qRT-PCR and western blot. Telomerase activity was assessed with TRAP method. Neuron apoptosis and senescence were assessed by TUNEL and immunofluorescence assays. Inflammatory cytokines and oxidative stress-indicators were examined using commercial kits. EA intervention at both GV20 and GB20 acupoints reduced infarct volumes (2.48 ± 1.89 vs. 29.56 ± 2.55), elevated the telomerase activity (0.84 ± 0.08 vs. 0.34 ± 0.09), and upregulated the levels of total TERT protein (0.61 ± 0.09 vs. 0.21 ± 0.05) and mitochondrial TERT (Mito-TERT; 0.54 ± 0.03 vs. 0.27 ± 0.03) in hippocampus tissues of MCAO/R rats. EA intervention attenuated motor dysfunction (112.00 ± 6.69 vs. 30.02 ± 2.60) and improved spatial learning (23.87 ± 1.90 vs. 16.23 ± 1.45) and memory ability (8.38 ± 1.06 vs. 4.13 ± 1.13) of rats with cerebral I/R injury. In addition, EA intervention significantly attenuated histopathological changes of injured neurons, mitigated neuron apoptosis (32.27 ± 5.52 vs. 65.83 ± 4.31) and senescence in MCAO/R rats, as well as inhibited excessive production of inflammatory cytokines and attenuated oxidative stress. However, the above therapeutic efficiency of EA intervention in MCAO/R rats was partly eliminated by TERT knockdown. EA intervention at GB20 and GV20 acupoints exerted a protective role in cerebral I/R injury partly through restoring TERT function, implying the clinical potential of EA treatment in the treatment of ischemic stroke.

Background and Purpose: Motor impairment is a common occurrence in patients with acute basal ganglia (BG) ischemic stroke (ABGIS). However, the underlying mechanisms of poststroke motor dysfunction remain incompletely elucidated. In this study, we employed multifrequency band wavelet transform-based amplitude of low-frequency fluctuations (Wavelet-ALFFs) to investigate the alterations of spontaneous regional neural activity in patients with ABGIS. Methods: A total of 39 ABGIS patients with motor dysfunction and 45 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. Wavelet-ALFF values were calculated in the conventional frequency band (0.01-0.08 Hz), slow-5 frequency band (0.01-0.027 Hz), and slow-4 frequency band (0.027-0.073 Hz). A two-sample t-test was performed to compare the Wavelet-ALFF values between the two groups with sex as a covariate and Gaussian random field (GRF) theory (voxel p < 0.001, cluster p < 0.05, two-tailed) was used for the multiple corrections. Furthermore, spearman correlation analysis was performed to assess the relationship between alterations in regional neural activity between Fugl-Meyer Assessment (FMA) and National Institutes of Health Stroke Scale (NIHSS) scores. Results: In comparison to HCs, patients with ABGIS showed significantly increased Wavelet-ALFF in the left middle temporal gyrus (MTG) and decreased Wavelet-ALFF in the right inferior frontal operculum (IFO) across all three frequency bands (conventional, slow-4, and slow-5). In the left superior occipital gyrus (SOG), Wavelet-ALFF was decreased in the conventional frequency band but increased in the slow-4 frequency band. Additionally, patients with ABGIS demonstrated reduced Wavelet-ALFF in the right superior temporal gyrus (STG) in the conventional and slow-4 frequency bands. In the slow-5 frequency band, increased Wavelet-ALFF was observed in the left calcarine cortex (CC), left middle frontal gyrus (MFG), left supramarginal gyrus (SMG), and left postcentral gyrus (PCG), while decreased Wavelet-ALFF was noted in the right precuneus (PCu). Correlation analysis revealed that increased Wavelet-ALFF in the left CC in the slow-5 frequency band was positively correlated with the FMA score. No other correlations were detected in the conventional and slow-4 frequency bands. Conclusions: The altered spontaneous neural activity was frequency-specific in patients with ABGIS, and the slow-5 frequency band exhibited better results. Furthermore, the relationship between spontaneous brain activity and clinical characteristics highlighted patterns of neural alterations associated with motor dysfunction. These findings may provide novel insights into the neural mechanisms underlying motor dysfunction in ABGIS.

Rapid thrombolysis is very important to reduce complications caused by vascular blockage. A promising approach for improving thrombolysis efficiency is utilizing the permanent magnetically actuated locomotion of nanorobots. However, the thrombolytic drug transportation efficiency is challenged by in-plane rotating locomotion and the insufficient drug penetration limits further improvement of thrombolysis. Inspired by ciliary movement for cargo transportation in human body, in this study, cilia-mimic locomotion of magnetic colloidal collectives is realized under torque-force vortex magnetic field (TFV-MF) by a designed rotating permanent magnet assembly. This cilia-mimic locomotion mode can generate more disturbances to the fluids to improve thrombolytic drug transportation and the increased height and area of colloidal collectives boosted the imaging capability. In addition, low-intensity ultrasound is applied to enhance colloids infiltration by producing the fiber breakage and inducing erythrocyte deformation. In vitro thrombolytic experiments demonstrate that the thrombolysis efficiency increased by 16.2 times compared with that of pure tissue plasminogen activator (tPA) treatments. Furthermore, in vivo rat models of femoral vein thrombosis confirmed that this approach can achieve blood flow recanalization more quickly. The proposed cilia-mimic locomotion of magnetic colloidal collectives combined with low-intensity ultrasound irradiation mode provides a new insight of therapeutic interventions for vascular thrombus by enhancing drug penetration.

Ischemic stroke, a major cause of disability and the second leading cause of death, poses a significant public health challenge. Post-stroke inflammation can harm the blood-brain barrier and worsen neurological deficits, which are key factors in neuronal damage in patients with ischemic stroke. Microglia are crucial in the central nervous system, involved in inflammation, neuronal damage, and repair after cerebral ischemia. While cellular immune metabolism has been widely studied, its role in ischamic stroke remains unclear.

This review aims to examine how inflammation affects the phenotypic characteristics of immune cells after ischemic stroke and to explore the effects of the immune metabolic microenvironment on the phenotypic profiles and functions of microglia in ischemic stroke.

The review refers to the available literature in PubMed, searching for critical terms related to Ischemic stroke, neuroinflammation, microglia, and immunometabolism.

In this review, we found that during stroke progression, microglia can dynamically switch between pro-inflammatory and anti-inflammatory phenotypes. Microglial glycometabolism includes oxidative phosphorylation and glycolysis, and lipid metabolism involves lipid synthesis and breakdown. Modulating the production of inflammatory mediator precursors can induce an anti-inflammatory phenotype in microglia.

Thus, studying microglial metabolic pathways and their products may offer new insights for ischemic stroke treatment.

The incidence of stroke ranks third among the leading causes of mortality worldwide. It has the characteristics of high morbidity, high disability rate and high recurrence rate. The current risk associated with stroke surgery is exceedingly high. It may potentially outweigh the benefits and fail to ameliorate the cerebral tissue damage following ischemia. Therefore, pharmacological intervention assumes paramount importance. The use of thrombolytic drugs is most common in the treatment of stroke; however, its efficacy is limited due to its time-sensitive nature and propensity for increased bleeding. Over the past few years, the treatment of stroke has witnessed a surge in interest towards neuroprotective drugs that possess the potential to enhance neurological function. The PDE4D gene has been demonstrated to have a positive correlation with the risk of ischemic stroke. Additionally, the utilization of phosphodiesterase 4 inhibitors can enhance synaptic plasticity within the neural circuitry, regulate cellular metabolism, and prevent secondary brain injury caused by impaired blood flow. These mechanisms collectively facilitate the recovery of functional neurons, thereby serving as potential therapeutic interventions. Therefore, the comprehensive investigation of phosphodiesterase 4 as an innovative pharmacological target for stroke injury provides valuable insights into the development of therapeutic interventions in stroke treatment. This review is intended for, but not limited to, pharmacological researchers, drug target researchers, neurologists, neuromedical researchers, and behavioral scientists.

Few clinical studies perform detailed analyses of subtypes of intracranial hemorrhage (ICH) after mechanical thrombectomy (MT) used to treat acute ischemic stroke. Symptomatic intracranial hemorrhage (sICH) is a formidable complication of MT and is widely used in clinical trials as a safety outcome. However, variable definitions of sICH are used across clinical studies.

To radiographically subcategorize post-MT ICH development within this large cohort and examine overlap with sICH. Second, to examine the agreement of this definition of sICH with local site-reported occurrences of sICH to see how sICH rates change with modifications of the definitions used.

A large cohort of patients treated with MT for acute ischemic stroke (n=1395) was analyzed to (1) radiographically characterize hemorrhagic subtypes of intracranial hemorrhage (ICH) occurring after MT; (2) examine associations of hemorrhagic subtypes with sICH; and (3) compare core laboratory-adjudicated occurrences of sICH with site-reported sICH.

The overall rate of ICH was 552/1395 patients (39.6%), and the overall rate of sICH was 47/1395 (3.4%). The most common type of ICH was hemorrhagic infarction type 1 (HI1), which represented 45.3% of all ICH cases- followed by HI2 (31.5%) and subarachnoid hemorrhage (SAH, 29.2%). Parenchymal hematoma 2 (PH2) represented only 3.3% of all ICH cases. Of the PH2 hemorrhages, only 33.3% were determined to be symptomatic. Of sICH cases, the most common ICH subtypes were HI2 (48.9%) and SAH (38.3%). Comparison of sICH rates as determined by core laboratory adjudication versus local site-reported results showed that only 14 patients were identified as having sICH with both definitions, with 47 patients total with sICH according to one definition, but not the other.

Results of this analysis demonstrate the radiographic subtypes of ICH and also highlight the limitations of variable criteria used to define sICH, suggesting that it might be appropriate to revisit how sICH is defined post-MT.

Clinical trial NCT03845491.

Evidence for Mobile Stroke Units (MSUs) demonstrates that onset to treatment times for intravenous thrombolysis can be reduced and access to mechanical thrombectomy might be improved. Despite growing use of MSUs internationally, to date there have been no studies in NHS England and NHS Wales exploring the acceptability of MSUs to clinicians, patient and public representatives and other key stakeholders, which are important when considering potential feasibility and implementation.

This study used a mixed methods design with a cross-sectional survey and qualitative workshops and interviews between October 2023 to May 2024. Survey data were collected from clinicians involved in emergency stroke care. Qualitative data involved clinical and non-clinical professionals involved in stroke care alongside patient and public representatives with experience of stroke. Survey data were descriptively analysed while content analysis was used on open-ended questions. Qualitative data were thematically analysed, prior to triangulation using a convergent coding matrix.

The study results, drawn from 25 respondents to the survey and 21 participants in qualitative workshops, found that almost all participants had positive affective attitudes to the concept of MSUs. However, several key areas of concern were identified that need to be addressed prior to implementing MSUs. These concerns included how MSUs would be staffed; whether and how telemedicine could contribute; the types of economic impacts; extent to which triage systems could accurately identify stroke patients for MSUs to attend; where the base location and geographic coverage of MSUs should be, the impact of MSUs on equitable access to stroke care, and how to improve public awareness of MSUs.

Whilst MSUs are mostly acceptable to key stakeholders, numerous areas of concern need to be addressed prior to MSU implementation. We recommend further research to address these issues prior to implementation in the NHS.

Neurodegenerative diseases (NDs) are caused by progressive neuronal death and cognitive decline. Epigallocatechin 3-gallate (EGCG) is a polyphenolic molecule in green tea as a neuroprotective agent. This review evaluates the therapeutic effects of EGCG and explores the molecular mechanisms that show its neuroprotective properties. EGCG protects neurons in several ways, such as by lowering oxidative stress, stopping Aβ from aggregation together, changing cell signaling pathways, and decreasing inflammation. Furthermore, it promotes autophagy and improves mitochondrial activity, supporting neuronal survival. Clinical studies have demonstrated that EGCG supplementation can reduce neurodegenerative biomarkers and enhance cognitive function. This review provides insights into the molecular mechanisms and therapeutic potential of EGCG in treating various NDs. EGCG reduces oxidative stress by scavenging free radicals and enhancing antioxidant enzyme activity, aiding neuronal defense. It also protects neurons and improves cognitive abilities by inhibiting the toxicity and aggregation of Aβ peptides. It changes important cell signaling pathways like Nrf2, PI3K/Akt, and MAPK, which are necessary for cell survival, cell death, and inflammation. Additionally, it has strong anti-inflammatory properties because it inhibits microglial activation and downregulates pro-inflammatory cytokines. It improves mitochondrial function by reducing oxidative stress, increasing ATP synthesis, and promoting mitochondrial biogenesis, which promotes neurons' survival and energy metabolism. In addition, it also triggers autophagy, a cellular process that breaks down and recycles damaged proteins and organelles, eliminating neurotoxic aggregates and maintaining cellular homeostasis. Moreover, it holds significant promise as an ND treatment, but future research should focus on increasing bioavailability and understanding its long-term clinical effects. Future studies should focus on improving EGCG delivery and understanding its long-term effects in therapeutic settings. It can potentially be a therapeutic agent for managing NDs, indicating a need for further research.

This study evaluates the efficacy of deep learning models in identifying infarct tissue on computed tomography perfusion (CTP) scans from patients with acute ischemic stroke due to large vessel occlusion, specifically addressing the potential influence of varying noise reduction techniques implemented by different vendors. We analyzed CTP scans from 60 patients who underwent mechanical thrombectomy achieving a modified thrombolysis in cerebral infarction (mTICI) score of 2c or 3, ensuring minimal changes in the infarct core between the initial CTP and follow-up MR imaging. Noise reduction techniques, including principal component analysis (PCA), wavelet, non-local means (NLM), and a no denoising approach, were employed to create hemodynamic parameter maps. Infarct regions identified on follow-up diffusion-weighted imaging (DWI) within 48 hours were co-registered with initial CTP scans and refined with ADC maps to serve as ground truth for training a data-augmented U-Net model. The performance of this convolutional neural network (CNN) was assessed using Dice coefficients across different denoising methods and infarct sizes, visualized through box plots for each parameter map. Our findings show no significant differences in model accuracy between PCA and other denoising methods, with minimal variation in Dice scores across techniques. This study confirms that CNNs are adaptable and capable of handling diverse processing schemas, indicating their potential to streamline diagnostic processes and effectively manage CTP input data quality variations.

Stroke is a condition characterized by damage to the cerebral vasculature from various causes, resulting in focal or widespread brain tissue damage. Prior neuroimaging research has demonstrated that individuals with stroke present structural and functional brain abnormalities, evident through disruptions in motor, cognitive, and other vital functions. Nevertheless, there is a lack of studies on alterations in static and dynamic functional network connectivity in the brains of stroke patients. Fifty stroke patients and 50 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning. Initially, the independent component analysis (ICA) method was utilized to extract the resting-state network (RSN). Subsequently, the disparities in static functional network connectivity both within and between networks among the two groups were computed and juxtaposed. Following this, five consistent and robust dynamic functional network connectivity (dFNC) states were derived by integrating the sliding time window method with k-means cluster analysis, and the distinctions in dFNC between the groups across different states, along with the intergroup variations in three dynamic temporal metrics, were assessed. Finally, a support vector machine (SVM) approach was employed to discriminate stroke patients from HCs using FC and FNC as classification features. Comparing the stroke group to the healthy control (HC) group, the stroke group exhibited reduced intra-network functional connectivity (FC) in the right superior temporal gyrus of the ventral attention network (VAN), the left calcarine of the visual network (VN), and the left precuneus of the default mode network (DMN). Regarding static functional network connectivity (FNC), we identified increased connectivity between the executive control network (ECN) and dorsal attention network (DAN), salience network (SN) and DMN, SN-ECN, and VN-ECN, along with decreased connectivity between DAN-DAN, ECN-SN, SN-SN, and DAN-VN between the two groups. Noteworthy differences in dynamic FNC (dFNC) were observed between the groups in states 3 to 5. Moreover, stroke patients demonstrated a significantly higher proportion of time and longer mean dwell time in state 4, alongside a decreased proportion of time in state 5 compared to HC. Finally, utilizing FC and FNC as features, stroke patients could be distinguished from HC with an accuracy exceeding 70% and an area under the curve ranging from 0.8284 to 0.9364. In conclusion, our study reveals static and dynamic changes in large-scale brain networks in stroke patients, potentially linked to abnormalities in visual, cognitive, and motor functions. This investigation offers valuable insights into the neural mechanisms underpinning the functional deficits observed in stroke, thereby aiding in the diagnosis and development of targeted therapeutic interventions for affected individuals.

The mechanism of remimazolam, a benzodiazepine that activates γ-aminobutyric acid a (GABAa) receptors, in cerebral ischemia/reperfusion (I/R) injury is not well understood. Therefore, we explored whether remimazolam activates protein kinase B (AKT)/glycogen synthase kinase-3β (GSK-3β)/nuclear factor erythroid 2-related factor 2 (NRF2) to attenuate brain I/R injury in transcerebral I/R-injured rats and transoxygenic glucose deprivation/reperfusion (OGD/R)-injured SY5Y cells.

Remimazolam was added at the beginning of cell and rat reperfusion, and the PI3K/AKT inhibitor LY294002 was added to inhibit the AKT/GSK-3β/NRF2 pathway 24 h before cellular OGD/R treatment and 30 min before rat brain I/R treatment. The viability and apoptosis rate of SY5Y cells, neurological deficit score, cerebral infarction volume and morphological changes of rat brain cells as well as the protein expression of Bax, Bcl2, Caspase 3, Cleaved-Caspase 3 and the number of TdT-mediated dUTP Nick-End Labeling (TUNEL)-positive cells in the penumbral region were detected. Reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), NRF2, heme oxygenase 1 (HO-1), AKT, P-AKT, GSK-3β, P-GSK-3β protein expression, and nuclear translocation of NRF2 were measured in cell and animal assays.

Reduced SY5Y cell viability and increased apoptosis caused by OGD/R injury, elevated neurological deficit scores and cerebral infarct volume induced by brain I/R injury in rats, cerebral cell injury, as well as elevated Bax, Cleaved-Caspase 3, decreased Bcl2, and increased number of TUNEL-positive cells in rat brain tissue were all moderated by remimazolam. Decreased GSH-Px, SOD and Elevated MDA, ROS induced by OGD/R-injured SY5Y cells and brain I/R-injured rats were moderated by remimazolam. Meanwhile, remimazolam increased NRF2, HO-1, P-AKT, P-GSK-3β, and the nuclear accumulation of NRF2. The PI3K/AKT inhibitor LY294002 reversed the role of remimazolam in brain I/R injury.

This study demonstrates that remimazolam activates the AKT/GSK-3β/NRF2 pathway, thereby attenuating oxidative stress and apoptosis to protect against brain I/R injury.

Spasticity commonly occurs in individuals after experiencing a stroke, impairing their hand function and limiting activities of daily living (ADLs). In this paper, we introduce an exoskeletal aid, combined with a set of augmented reality (AR) games consisting of the Rehabotics rehabilitation solution, designed for individuals with upper limb spasticity following stroke.

Our study, involving 60 post-stroke patients (mean ± SD age: 70.97  ±  4.89 years), demonstrates significant improvements in Ashworth Scale (AS) scores and Box and Block test (BBT) scores when the Rehabotics solution is employed.

The intervention group showed slightly greater improvement compared to the control group in terms of the AS (-0.23, with a confidence interval of -0.53 to 0.07) and BBT (1.67, with a confidence interval of 1.18 to 2.16). Additionally, the Rehabotics solution was particularly effective for patients with more severe deficits. Patients with an AS score of 3 showed more substantial improvements, with their AS scores increasing by -1.17 ± 0.39 and BBT scores increasing by -4.83 ± 0.72.

These findings underscore the potential of wearable hand robotics in enhancing stroke survivors' hand rehabilitation, emphasizing the need for further investigations into its broader applications.

Nerve injury represents the primary reason of mortality and disability in ischemic stroke, but effective drug delivery to the region of cerebral ischemia and hypoxia poses a significant challenge in neuroprotective treatment. To address these clinical challenges, a biomimetic nanomotor, Pt@LF is designed, to facilitate deep delivery of neuroprotective agents and inhibit ferroptosis in ischemic stroke. Pt@LF traverses the blood-brain barrier (BBB) and penetrates into deep cerebral ischemic-hypoxic areas due to the active targeting capacity of apo-lactoferrin (Apo-LF) and the self-propelling motion properties of nanomotors. Subsequently, Pt@LF loosens thrombus and alleviates the "no reflow" phenomenon via mechanical thrombolysis. Thanks to the various enzyme-like abilities and multi-target ferroptosis inhibition capability, Pt@LF ameliorates the inflammatory microenvironment and rescues dying neurons. In conclusion, Pt@LF demonstrates efficiently deep penetration and neuroprotective effects in vitro and vivo. And this study provides a promising therapeutic platform for the treatment of ischemic stroke.

It has been proposed that colchicine may have the potential to prevent cardiovascular and cerebrovascular dysfunctions.

This study evaluated the impact of colchicine on preventing recurrent stroke in patients with both ischemic stroke (IS) and atrial fibrillation (AF).

A randomized, double-blinded, placebo-controlled trial was conducted at Golestan Hospital (Ahvaz, Iran) over one year, involving IS patients with AF. Demographic and clinical data were collected from the participants, who were then assigned to either the intervention or placebo groups. The experimental group was administered colchicine at a dosage of 0.05 mg twice daily for one year, while the control group received a placebo at a comparable dosage over the same timeframe.

In one year, 108 patients completed the study. There were 55 patients in the intervention group and 53 patients in the placebo group. During the second trimester of the trial, three patients in the colchicine group and 10 patients in the placebo group experienced recurrent strokes. Gastrointestinal issues were the most commonly reported complications (33 cases) among the two groups, followed by myalgia (8 patients). There were significant differences in the frequency of recurrent stroke and serum levels of C-reactive protein (CRP) between the colchicine and placebo groups (p < 0.05) after intervention.

In this study, colchicine was effective in reducing recurrent stroke and CRP levels in IS patients with AF compared to the control group. Further randomized controlled trials with larger sample sizes and extended durations are recommended to validate the results of this trial.

To identify the molecular targets of mesenchymal stem cell (MSC)-derived exosomes in treating cerebral ischemia and elucidate their therapeutic mechanisms.

We utilized a mouse model of middle cerebral artery occlusion and treated mice with umbilical cord mesenchymal stem cells derived exosomes. Proteomic analysis identified AAK1(AP2 associated kinase 1) as a key target protein. Functional studies confirmed that AAK1 modulates the NF-κB signaling pathway in ischemic stroke. MicroRNA profiling, bioinformatic prediction and cell experiments identified miR-664a-5p as the specific microRNA regulating AAK1 expression. Finally, we validated the therapeutic effects of umbilical cord mesenchymal stem cell-derived exosomes using engineered miR-664a-5p-deficient exosomes.

Our findings demonstrate that umbilical cord mesenchymal stem cells-derived exosomes exert neuroprotective effects in ischemic stroke by modulating the AAK1/NF-κB axis via miR-664a-5p.

This study provides novel insights into the therapeutic mechanism of mesenchymal stem cell-derived exosomes in ischemic stroke, highlighting their potential for developing exosome-based therapies.

Acute cerebral ischemia is a leading cause of death and disability, particularly among old adults. The narrow therapeutic window and risk of hemorrhagic transformation largely limit patient eligibility for the current treatment. The neuroinflammatory signaling pathway involving the prostaglandin E2 (PGE2) receptor subtype EP2 has now been clarified to contribute to the secondary neurotoxicity following ischemic stroke. We previously demonstrated the feasibility of pharmacologically targeting EP2 for ischemic stroke using an EP2 antagonist in a mouse model of transient middle cerebral artery occlusion. Herein, we evaluated the effects of a second-generation EP2 antagonist with improved potency and selectivity in a mouse model of thrombotic stroke, the most common type of stroke. We found that the EP2 antagonist, when administered hours after an ischemic stroke induced within motor and somatosensory cortices by photoactivation of a light-sensitive dye Rose Bengal, reduced cortical infarction in a dose-dependent manner. EP2 inhibition also improved the poststroke body weight recovery and reduced neurological impairments in locomotor and cognitive functions, revealed by a panel of behavioral tests. These broad benefits support the feasibility of targeting the PGE2/EP2 axis-mediated neuroinflammatory pathway as a novel strategy to alleviate the ischemic brain injury caused by thrombotic occlusion and accelerate poststroke recovery.

The objective of this study was to evaluate the feasibility of point-of-care testing (POCT) devices for N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement in prehospital settings, with the aim of improving the speed and accuracy of stroke diagnosis, thereby facilitating quicker and more effective patient care.

Prehospital blood samples were collected from suspected stroke patients, and NT-proBNP levels were measured using a POCT device in ambulances and hospitals. Results from the NT-proBNP POCT and smartphone images were analyzed. Plasma samples underwent Elecsys proBNP II immunoassay after storage at -80ºC.

A total of 121 suspected stroke patients were included in the study. The correlation between POCT measured by the POCT and immunoassay for NT-proBNP was strong (R = 0.926). Smartphone images also strongly correlated with POCT values at 10 min (R²=0.9716) and 15 min (R²=0.9405). Stability analysis of samples showed consistent NT-proBNP results and a high correlation (R = 0.907) was observed between plasma and whole blood samples for NT-proBNP POCT.

This study highlights the potential of NT-proBNP POCT devices in ambulances to expedite stroke diagnosis and management within 10 min. Smartphone integration further enhances efficiency, adding advancement in prehospital stroke management.

Ischemic stroke and reperfusion injury result in neuronal damage and dysfunction associated with oxidative stress, leading to overproduction of cellular reactive oxygen species (ROS) and reactive nitrogen species (RNS). In situ monitoring of the transient ROS and RNS effluxes during rapid pathologic processes is crucial for understanding the relationship between progression of cell damage and role of oxidative stress, and developing the corresponding neuroprotective strategies. Herein, we built oxygen glucose deprivation (OGD) and mild hypothermic (MH) models to mimic the in vitro conditions of ischemic stroke and MH treatment. We used scanning electrochemical microscopy (SECM) to in situ monitor H2O2 and nitric oxide (NO) effluxes from HT22 cells under the OGD and MH treatment conditions. Through quantitative analysis of the H2O2 and NO efflux results, we found that the cellular oxidative stress was primarily manifested through ROS release under OGD conditions, and the MH treatment partially suppressed the excessive H2O2 and NO production induced by reoxygenation. Moreover, the synergistic therapeutic effect of MH with antioxidant treatment significantly reduced the oxidative stress and enhanced the cell survival. Our work reveals the crucial role of oxidative stress in OGD and reperfusion processes, and the effective improvement of cell viability via combination of MH with antioxidants, proposing promising therapeutic interventions for ischemic stroke and reperfusion injury.

Despite improvements in the treatment of acute ischemic stroke (AIS), some patients still suffer from functional impairments, indicating the poor understanding of pathophysiologic process of AIS. Inflammation plays an important role in the pathophysiology of AIS. The purpose of the study was to investigate the peripheral inflammation in different subtypes of AIS.

Here, retrospective data from AIS with large vessel occlusion (LVO) and small vessel occlusion (SVO), and healthy controls, were initially analyzed. Then, flow cytometry was performed to evaluate the levels of peripheral naïve and memory T-cells. Finally, we characterized the T cell receptors (TCR) repertoire using high-throughput sequencing.

Elevated levels of leukocytes, neutrophils, and neutrophil-to-lymphocyte ratio (NLR), and decreased levels of lymphocytes were found in LVO group than that in SVO group, which were correlated with the severity of LVO. In addition, higher percentages of both effector memory (Tem) and central memory (Tcm) T cells, and lower percentage of naïve T cells in CD4+ and CD8+ T cells, were found in LVO group than that in SVO and healthy groups. Moreover, impaired TCR diversity, and different abundances of V-J gene combinations and amino acid sequences, were found in LVO as compared with healthy group, which would be potential biomarkers for LVO diagnosis.

In conclusion, AIS with LVO can rapidly induce peripheral immune response, which provides new insight into the understanding of pathophysiology of AIS.

Stroke remains the 3rd leading cause of long-term disability globally. Over the past decade, mesenchymal stem cell (MSC) transplantation has been proven as an effective therapy for ischemic stroke. However, the mechanism of MSC-derived exosomal lncRNAs during cerebral ischemia/reperfusion (I/R) remains ambiguous. The oxygen-glucose deprivation/reoxygenation (OGD/R) and middle cerebral artery occlusion (MCAO) rat model were generated. MSCs were isolated and characterized by flow cytometry and histochemical staining, and MSC exosomes were purified and characterized by transmission electron microscopy, flow cytometry and Western blot. Western blot, RT-qPCR and ELISA assay were employed to examine the expression or secretion of key molecules. CCK-8 and TUNEL assays were used to assess cell viability and apoptosis. RNA immunoprecipitation and RNA pull-down were used to investigate the direct association between krüppel-like factor 3 antisense RNA 1 (KLF3-AS1) and musashi-1(MSI1). Yin Yang 1 (YY1)-mediated transcriptional regulation was assessed by chromatin immunoprecipitation and luciferase assays. The histological changes and immunoreactivity of key molecules in brain tissues were examined by H&E and immunohistochemistry. MSCs were successfully isolated and exhibited directionally differential potentials. MSC exosomal KLF3-AS1 alleviated OGD/R-induced inflammation in SK-N-SH and SH-SY5Y cells via modulating Sphk1. Mechanistical studies showed that MSI1 positively regulated KLF3-AS1 expression through its direct binding to KLF3-AS1. YY1 was identified as a transcription activator of MSI1 in MSCs. Functionally, YY1/MSI1 axis regulated the release of MSC exosomal KLF3-AS1 to modulate sphingosine kinase 1 (Sphk1)/NF-κB pathway, thereby ameliorating OGD/R- or cerebral I/R-induced injury. MSCs promote the release of exosomal KLF3-AS1 to regulate Sphk1 through YY1/MSI axis and improve cerebral I/R injury.

Background: Routine activated partial thromboplastin time (APTT) and prothrombin time (PT) measurements do not indicate hypercoagulability in patients with acute myocardial infarction (AMI) and acute cerebral infarction (ACI). Methods: Hypercoagulability in patients with AMI or ACI was evaluated using a clot waveform analysis of the APTT or a small amount of tissue factor activation assay (sTF/FIXa). In the CWA, the derivative peak time (DPT), height (DPH), width (DPW), and area the under the curve (AUC) were evaluated. Results: The APTT did not indicate hypercoagulability, but the second DPT of CWA-sTF/FIXa was significantly shorter in patients with ACI than in healthy volunteers (HVs). The first DPH values of CWA-APTT and CWA-sTF/FIXa in patients with ACI and AMI were significantly higher than in HVs. In the receiver operating characteristic (ROC) analyses of ACI or AMI vs. non-thrombosis, the AUC was >0.800 in the DPHs of CWA-APTT and CWA-sTF/FIXa. The AUC of CWA-APTT and CWA-sTF/FIXa in patients with AMI and ACI was significantly higher than in HVs. The AUC/second DPT of CWA-APTT and CWA-sTF/FIXa in patients with AMI and ACI was significantly higher than in HVs. Regarding the ROC analyses of ACI or AMI vs. HVs, the AUC of ROC was higher than 0.800 in the AUC and AUC/second DPT of CWA-APTT and CWA-sTF/FIXa. Conclusions: The AUC/second DPT of CWA-APTT and CWA-sTF/FIXa may be a useful parameter for detecting a hypercoagulable state in patients with AMI and ACI.

Objective: This paper aims to address the clinical challenge of predicting the outcomes of stroke patients and proposes a comprehensive model called RGX to help clinicians adopt more personalized treatment plans. Impact Statement: The comprehensive model is first proposed and applied to clinical datasets with missing data. The introduction of the Shapley additive explanations (SHAP) model to explain the impact of patient indicators on prognosis improves the accuracy of stroke patient mortality prediction. Introduction: At present, the prediction of stroke treatment outcomes faces many challenges, including the lack of models to quantify which clinical variables are closely related to patient survival. Methods: We developed a series of machine learning models to systematically predict the mortality of stroke patients. Additionally, by introducing the SHAP model, we revealed the contribution of risk factors to the prediction results. The performance of the models was evaluated using multiple metrics, including the area under the curve, accuracy, and specificity, to comprehensively measure the effectiveness and stability of the models. Results: The RGX model achieved an accuracy of 92.18% on the complete dataset, an improvement of 11.38% compared to that of the most advanced state-of-the-art model. Most importantly, the RGX model maintained excellent predictive ability even when faced with a dataset containing a large number of missing values, achieving an accuracy of 84.62%. Conclusion: In summary, the RGX ensemble model not only provides clinicians with a highly accurate predictive tool but also promotes the understanding of stroke patient survival prediction, laying a solid foundation for the development of precision medicine.

Improved treatment options are urgently needed for neurological injuries resulting from trauma or iatrogenic events causing long-term disabilities that severely impact patients' quality of life. In vitro and animal studies have provided promising proof-of-concept examples of regenerative therapies using mesenchymal stromal cells (MSC) for a wide range of pathological conditions. Over the previous decade, various MSC-based therapies have been investigated in clinical trials to treat traumatic neurological injuries. However, while the safety and feasibility of MSC treatments has been established, the patient outcomes in these studies have not demonstrated significant success in the translation of MSC regenerative therapy for the treatment of human brain and spinal cord injuries. Herein, we have reviewed the literature and ongoing registered trials on the application of MSC for the treatment of traumatic brain injury, traumatic spinal cord injury, and peripheral nerve injury. We have focused on the shortcomings and technological hurdles that must be overcome to further advance clinical research to phase 3 trials, and we discuss recent advancements that represent potential solutions to these obstacles to progress.

Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite, the production of which in vivo is mainly regulated by dietary choices, gut microbiota, and the hepatic enzyme flavin monooxygenase (FMO), while its elimination occurs via the kidneys. The TMAO level is positively correlated with the risk of developing cardiovascular diseases. Recent studies have found that TMAO plays an important role in the development of ischemic stroke. In this review, we describe the relationship between TMAO and ischemic stroke risk factors (hypertension, diabetes, atrial fibrillation, atherosclerosis, thrombosis, etc.), disease risk, severity, prognostic outcomes, and recurrence and discuss the possible mechanisms by which they interact. Importantly, TMAO induces atherosclerosis and thrombosis through lipid metabolism, foam cell formation, endothelial dysfunction (via inflammation, oxidative stress, and pyroptosis), enhanced platelet hyper-reactivity, and the upregulation and activation of vascular endothelial tissue factors. Although the pathogenic mechanisms underlying TMAO's aggravation of disease severity and its effects on post-stroke neurological recovery and recurrence risk remain unclear, they may involve inflammation, astrocyte function, and pro-inflammatory monocytes. In addition, this paper provides a summary and evaluation of relevant preclinical and clinical studies on interventions regarding the gut-microbiota-dependent TMAO level to provide evidence for the prevention and treatment of ischemic stroke through the gut microbe-TMAO pathway.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a ubiquitous neurotrophic factor that exhibits a variety of physiological functions and plays a critical role in the exploitation of therapeutic potential across a range of diseases, including cardiovascular disorders, nervous system diseases, metabolic imbalances, and cancers. In the context of cardiac diseases, MANF significantly promotes cardiomyocyte survival and improves cardiac functionality. Furthermore, MANF not only provides neuroprotection by shielding neurons from damage and promoting nerve regeneration in neurological disorders, but also involves in insulin resistance, lipid metabolism disturbances and fat-containing liver lesions. However, the oncogenic or tumor suppressive function of MANF in cancer remains unclear, requiring further investigation to elucidate its precise role in the process of cancer initiation and progression. This review aims to summarize the latest advancements in understanding the molecular pathways, intricate mechanisms, and therapeutic potential of MANF in the prevention and treatment of various diseases, emphasizing its multifaceted contributions to health and disease management.

Stroke remains one of the major health challenges due to its high rates of mortality and long-term disability, necessitating the development of effective therapeutic treatment. This study aims to explore the neuroprotective effects of hypoxic postconditioning (HPC) using a cell-based 3D cortical ischemic-hypoxic injury model. Our model employs murine cells to investigate HPC-induced modulation of glial cell reactivity and intercommunication post-oxygen-glucose deprivation-reoxygenation (OGD-R) injury. We found that a single HPC session (1HPC) provided the most significant neuroprotection post-OGD-R compared to multiple intermittent hypoxic treatments, evidenced by improved spheroidal structure, enhanced cell survival and reduced apoptosis, optimal modulation of neuronal phenotypes, dampened ischemic responses, and augmented neurite outgrowth of spheroids. Furthermore, 1HPC suppressed both pro-inflammatory A1 and anti-inflammatory A2 astrocyte phenotypes despite the induction of astrocyte activation while reducing microglial activation with inhibited M1 and M2 reactive states. This was accompanied by a decrease in gene expression of the pro-inflammatory cytokines essential to microglia-astrocyte signaling, collectively suggesting a shift of glial cells away from their traditional reactive states for neuroprotection. This study highlights the potential of 1HPC as a novel therapeutic intervention for ischemic injury via the modulation of neuroprotective glial reactivity. Moreover, the 3D cortical ischemic-hypoxic injury model employed here holds enormous potential serving as a disease model to further elucidate the underlying mechanism of HPC, which can also extend to the applications in brain regeneration, drug development, and the modeling of neural diseases.

The purpose of this study is to the relationship between peripheral apolipoproteins and the prognosis of patients with acute ischemic stroke (AIS) after thrombolysis.

A total of 231 AIS patients with thrombolysis was enrolled. Serum apolipoproteins were measured on admission after thrombolysis. All patients enrolled were followed up for 90 days. Their functional outcomes were assessed by the modified Rankin Scale (mRS). Good functional outcome was considered as mRS < 3. Logistic regression was applied to assess the association between serum apolipoproteins and the mRS at 90 days.

In multivariate analysis,1) ApoB (OR=0.099, 95%CI=0.017∼0.575, p=0.010) and ApoB/ApoA-1(OR=0.113, 95%CI=0.015∼0.868, p=0.036) were independent risk factors of good functional outcome at 90 days. 2). there were significant differences in the mRS score distribution at 90 days in groups according to the ROC cutoff values of ApoB (0.85g/L) and ApoB/ApoA-1 ratio (0.61) (all p<0.05).

Our findings demonstrated ApoB and ApoB/apoA-1 ratio were independent risk factors for good functional outcome at 90 days, and the ApoB level below 0.85g/L and ApoB/ApoA-1 ratio below 0.61 could be associated with a better functional outcome in this study population.

Ischemic stroke(IS), a severe acute cerebrovascular disease, not only imposes a heavy economic burden on society but also presents numerous challenges in treatment. During the acute phase, while thrombolysis and thrombectomy serve as primary treatments, these approaches are restricted by a narrow therapeutic window. During rehabilitation, commonly used neuroprotective agents struggle with their low drug delivery efficiency and inadequate preclinical testing, and the long-term pharmacological and toxicity effects of nanomedicines remain undefined. Meanwhile, acupuncture as a therapeutic approach is widely acknowledged for its effectiveness in treating IS and has been recommended by the World Health Organization (WHO) as an alternative and complementary therapy, even though its exact mechanisms remain unclear. This review aims to summarize the known mechanisms of acupuncture and electroacupuncture (EA) in the treatment of IS. Research shows that acupuncture treatment mainly protects the neurovascular unit through five mechanisms: 1) reducing neuronal apoptosis and promoting neuronal repair and proliferation; 2) maintaining the integrity of the blood-brain barrier (BBB); 3) inhibiting the overactivation and polarization imbalance of microglia; 4) regulating the movement of vascular smooth muscle (VSM) cells; 5) promoting the proliferation of oligodendrocyte precursors. Through an in-depth analysis, this review reveals the multi-level, multi-dimensional impact of acupuncture treatment on the neurovascular unit (NVU) following IS, providing stronger evidence and a theoretical basis for its clinical application.

The precise mapping of collateral circulation and ischemic penumbra is crucial for diagnosing and treating acute ischemic stroke (AIS). Unfortunately, there exists a significant shortage of high-sensitivity and high-resolution in vivo imaging techniques to fulfill this requirement. Herein, a contrast enhanced susceptibility-weighted imaging (CE-SWI) using the minimalist dextran-modified Fe3O4 nanoparticles (Fe3O4@Dextran NPs) are introduced for the highly sensitive and high-resolution AIS depiction under 9.4 T for the first time. The Fe3O4@Dextran NPs are synthesized via a simple one-pot coprecipitation method using commercial reagents under room temperature. It shows merits of small size (hydrodynamic size 25.8 nm), good solubility, high transverse relaxivity (r2) of 51.3 mM-1s-1 at 9.4 T, and superior biocompatibility. The Fe3O4@Dextran NPs-enhanced SWI can highlight the cerebral vessels readily with significantly improved contrast and ultrahigh resolution of 0.1 mm under 9.4 T MR scanner, enabling the clear spatial identification of collateral circulation in the middle cerebral artery occlusion (MCAO) rat model. Furthermore, Fe3O4@Dextran NPs-enhanced SWI facilitates the precise depiction of ischemia core, collaterals, and ischemic penumbra post AIS through matching analysis with other multimodal MR sequences. The proposed Fe3O4@Dextran NPs-enhanced SWI offers a high-sensitivity and high-resolution imaging tool for individualized characterization and personally precise theranostics of stroke patients.