Stroke is a leading cause of disability and death worldwide. In this study, we identified potential therapeutic targets for stroke using a data mining, network analysis, enrichment, and docking analysis approach. We first identified 1991 genes associated with stroke from two publicly available databases: GeneCards and DisGeNET. We then constructed a protein-protein interaction (PPI) network using the STRING database and identified 1301 nodes and 5413 edges. We used Metascape to perform GO enrichment analysis and KEGG pathway enrichment analysis. The results of these analyses identified ten hub genes (TNF, IL6, ACTB, AKT1, IL1B, TP53, VEGFA, STAT3, CASP3, and CTNNB1) and five KEGG pathways (cancer, lipid and atherosclerosis, cytokine-cytokine receptor interaction, AGE RAGE signaling pathway in complications, and TNF signaling pathway) that are enriched in stroke genes. We then performed molecular docking analysis to screen potential drug candidates for these targets. The results of this analysis identified several promising drug candidates that could be used to develop new therapeutic strategies for stroke.

Stroke is a serious cerebrovascular disease that is categorized into two types: ischemic and hemorrhagic. The pathological mechanisms of ischemic stroke are complex and diverse, encompassing processes such as neuroinflammation and apoptosis. The pathological processes of hemorrhagic stroke primarily involve the disruption of the blood-brain barrier and cerebral edema. Western medical treatment methods show certain effectiveness during the acute phase of stroke, but they are limited by a narrow therapeutic window and secondary injuries. Traditional Chinese medicine (TCM) has a long history and unique advantages in treating stroke. Studies confirm that active compounds derived from TCM exert multi-pathway, multi-target effects, significantly improving therapeutic outcomes and reducing adverse reactions. However, due to the complexity of the components in TCM, research on monomeric components still faces challenges. This article reviews the relevant research progress published in domestic and international journals over the past twenty years regarding the mechanisms of action of monomeric components of TCM in the treatment of stroke, aiming to provide insights and references for the clinical application of TCM in stroke treatment and further new drug development.

The gray matter of the higher brain undergoes spreading depolarization (SD) in response to the increased metabolic demand of ischemia, promoting acute neuronal injury and death following stroke, traumatic brain injury, or sudden cardiac arrest. The mechanism linking ischemic failure of the Na+/K+ ATPase (NKA) pump to the immediate onset of a large inward current driving SD has remained a mystery because blockade of conventional ion channels does not prevent SD nor ischemic neuron death. The marine poison palytoxin (PLTX) specifically binds the NKA at picomolar concentrations, converting this transporter to an open cationic channel, causing sudden neuronal Na+ influx and K+ efflux. This pump failure, together with induction of a strong inward current, should evoke SD-like activity in gray matter. Indeed, 1-10 nM PLTX applied to live coronal brain slices of rodents induces a propagating depolarization remarkably like SD induced by oxygen/glucose deprivation (OGD). This PLTX depolarization (PD) mimicked other effects of OGD. In the neocortex, as an elevated light transmittance (LT) front passed by an extracellular pipette, a distinct negative DC shift indicated mass cell depolarization, whether induced by bath OGD or PLTX. Either treatment induced strong SD-like responses in the same higher or lower brain regions. Furthermore, we imaged identical real-time OGD-SD or PD effects upon live pyramidal neurons using 2-photon microscopy. Taken together, these findings support our proposal that an endogenous PLTX-like molecule may open the NKA to conduct Na+ influx/K+ efflux, thereby driving SD and, in its wake, ensuing neuronal damage.NEW & NOTEWORTHY With stroke, traumatic brain injury, or sudden cardiac arrest, there is no therapeutic drug to aid brain recovery. Within 2 min of severe ischemia, a wave of spreading depolarization (SD) propagates through affected gray matter. More SDs arise over hours, expanding the injury. This period represents a therapeutic window to inhibit recurring SD and reduce neuronal damage, but we do not understand the underlying molecular sequence. Here, we argue for a novel molecule to target.

It is well recognized that type II Diabetes (T2D) and overweight/obesity are established risk factors for stroke, worsening also their consequences. However, the underlying mechanisms by which these disorders aggravate outcomes are not yet clear limiting the therapeutic opportunities. To fill this gap, we characterized, for the first time, the effects of T2D and obesity on the brain repair mechanisms occurring 7 days after stroke, notably glial scarring. In the present study, by performing a 30-minute middle cerebral artery occlusion (MCAO) on db/db (obese diabetics mice) and db/+ (controls) mice, we demonstrated that obese and diabetic mice displayed larger lesions (i.e. increased infarct volume, ischemic core, apoptotic cell number) and worsened neurological outcomes compared to their control littermates. We then investigated the formation of the glial scar in control and db/db mice 7 days post-stroke. Our observations argue in favor of a stronger and more persistent activation of astrocytes and microglia in db/db mice. Furthermore, an increased deposition of extracellular matrix (ECM) was observed in db/db vs control mice (i.e. chondroitin sulfate proteoglycan and collagen type IV). Consequently, we demonstrated for the first time that the db/db status is associated with increased astrocytic and microglial activation 7 days after stroke and resulted in higher deposition of ECM within the damaged area. Interestingly, the injury-induced neurogenesis appeared stronger in db/db as shown by the labeling of migrating neuroblast. This increase appeared correlated to the larger size of lesion. It nevertheless raises the question of the functional integration of the new neurons in db/db mice given the observed dense ECM, known to be repulsive for neuronal migration. Carefully limiting glial scar formation after stroke represents a promising area of research for reducing neuronal loss and limiting disability in diabetic/obese patients.

Ischemic stroke is one of the major causes of death and disability in adults, bringing a significant economic burden to the society and families. Despite significant advancements in stroke treatment, focusing solely on neurons is insufficient for improving disease progression and prognosis. Astrocytes are the most ubiquitous cells in the brain, and they undergo morphological and functional changes after brain insults, which has been known as astrocyte reactivity. Transcriptomics have shown that reactive astrocytes (RA) are heterogeneous, and they can be roughly classified into neurotoxic and neuroprotective types, thereby affecting the development of central nervous system (CNS) diseases. However, the relationship between stroke and reactive astrocyte heterogeneity has not been fully elucidated, and regulating the heterogeneity of astrocytes to play a neuroprotective role may provide a new perspective for the treatment of stroke. Here we systematically review current advancements in astrocyte heterogeneity following ischemic stroke, elucidate the molecular mechanisms underlying their activation, and further summarize promising therapeutic agents and molecular targets capable of modulating astrocyte heterogeneity.

Ischemic stroke (IS) is a multifactorial disease caused by the interaction of a variety of environmental and genetic factors, which can lead to severe disability and heavy social burden. This study aimed to find potential biomarkers related to T cell exhaustion (TEX) in IS. Based on the GSE16561 dataset, differentially expressed genes (DEGs) were screened from IS and control groups, and their enriched biological pathways were explored. The TEX enrichment score for each sample was calculated using the GSEA algorithm, and the gene modules with the highest correlation with the TEX score were screened by WGCNA. Then, two machine learning algorithms were used to screen the key genes and test the correlation between the key genes and the level of immune cell infiltration. Potential drugs or molecular compounds that interact with key genes were predicted by searching DGIdb, and the drug-gene interaction network was visualized by Cytoscape software. Using GSE16561 dataset, we performed differential expression analysis and identified 482 DEGs. By weighted gene co-expression network analysis (WGCNA) and machine learning algorithms, we identified five key genes: CD163, LAMP2, PICALM, RGS2 and PIN1. Functional enrichment analysis revealed that these genes were involved in immune response and cellular processes, which were closely related to the level of immune cell infiltration. In addition, potential drug interactions were predicted using the drug-Gene Interaction database, providing avenues for future therapeutic strategies. This study enhances the understanding of TEX-related biomarkers in ischemic stroke and provides insights into the development of novel interventions aimed at improving patient outcomes.

Atrial fibrillation (AF) is one of the primary etiologies for ischemic stroke, and it is of paramount importance to delineate the risk phenotypes among elderly AF patients and to investigate more efficacious models for predicting stroke risk.

This single-center prospective cohort study collected clinical data and cardiac computed tomography angiography (CTA) images from elderly AF patients. The clinical phenotypes and left atrial appendage (LAA) radiomic phenotypes of elderly AF patients were identified through K-means clustering. The independent correlations between these phenotypes and stroke risk were subsequently analyzed. Machine learning algorithms-Logistic Regression, Naive Bayes, Support Vector Machine (SVM), Random Forest, and Extreme Gradient Boosting-were selected to develop a predictive model for stroke risk in this patient cohort. The model was assessed using the Area Under the Receiver Operating Characteristic Curve, Hosmer-Lemeshow tests, and Decision Curve Analysis.

A total of 419 elderly AF patients (≥ 65 years old) were included. K-means clustering identified three clinical phenotypes: Group A (cardiac enlargement/dysfunction), Group B (normal phenotype), and Group C (metabolic/coagulation abnormalities). Stroke incidence was highest in Group A (19.3%) and Group C (14.5%) versus Group B (3.3%). Similarly, LAA radiomic phenotypes revealed elevated stroke risk in patients with enlarged LAA structure (Group B: 20.0%) and complex LAA morphology (Group C: 14.0%) compared to normal LAA (Group A: 2.9%). Among the five machine learning models, the SVM model achieved superior prediction performance (AUROC: 0.858 [95% CI: 0.830-0.887]).

The stroke-risk prediction model for elderly AF patients constructed based on the SVM algorithm has strong predictive efficacy.

Stroke survivors have complex and long-term care needs requiring navigation of multiple care services and providers. Care coordination interventions provide wholistic care that meets the needs of the patient and improves their clinical outcomes and expectations. This systematic review will identify the key components of stroke care coordination interventions implemented in low and middle-income countries (LMICs) and assess their effectiveness on stroke outcomes such as motor recovery, cognitive function, mental health, stroke type and the role of stroke severity, type, and the nature of the interventions in influencing these outcomes.

Electronic databases, trial registries and non-database sources will be searched for published and unpublished studies. PubMed, LILACS, CINAHL via EBSCOhost, Scopus, Web of Science Core Collection, Cochrane CENTRAL and Google Scholar will be searched from 2000 to 31st May 2025, without language restriction. Trial registries including the WHO International Clinical Trials Registry Platform (ICTRP) and Clinicaltrials.gov will also be searched. Grey literature including dissertations, preprint repositories and conference proceedings will be searched. The key search terms include "stroke", "care integration", "continuity of care", "information exchange", "patient-centred care", "multidisciplinary care", "case management" and "low and middle-income countries", together with their alternative terms and synonyms, singular and plural forms and American and British spelling. Hand search of references of relevant studies will be carried out and experts in the field of stroke care coordination interventions will be contacted for their knowledge about any study missed by our searches. The studies will be collated in Rayyan and duplicates removed. Study selection will be done using a study selection flow chart developed from the pre-specified eligibility criteria defined by the PICOS elements (P ─ patient, I ─ intervention, C ─ comparator, O ─ outcomes and S ─study). Quality in the included studies will be assessed for risk of bias using the Cochrane Risk of Bias tool (version 2) for Randomized Controlled Trials (RoB 2) and ROBINS-I for Non-randomized Studies of Intervention. Data will be extracted using a pre-tested data extraction form developed from Microsoft Excel. Study selection, data extraction and risk of bias assessment will be conducted independently by two reviewers (SKJO and ADA). Disagreements between the reviewers will be resolved through discussion. Risk ratio (RR) will be used as the effect measure for binary/dichotomous outcomes. For continuous outcomes mean difference (MD) with standard deviation (SD) or standardized mean difference (SMD) for outcomes measured on different instruments or scales will be used as effect measures for expressing effectiveness of care coordination interventions. Random-effects meta-analyses will be employed to pool studies, and all effects estimates will be reported with their 95% confidence interval (CI). Heterogeneity will be assessed using the I2 statistic. The overall certainty of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE).

This review will attempt to identify the components of stroke-coordinated care interventions in low- and middle-income countries. It will assess whether these interventions improve clinical outcomes such as motor and cognitive functioning, mental wellbeing, mortality, and disability-adjusted life years (DALYs) of stroke survivors. The review will also explore how factors -such as stroke type, severity, and the nature of care coordination interventions (including the specific components) influence clinical, functional and psychosocial outcomes. The findings will help in determining the most effective care coordination interventions that should be adopted as care models to improve patient outcomes, whilst identifying evidence gaps for future research.

This systematic review and meta-analysis protocol has been registered in PROSPERO [CRD42024587311]. The findings of the study will be shared with the relevant stakeholders and disseminated through scientific conferences and peer review publications.

Background: Early studies indicated that the high content of tanshinone IIA (T-IIA) and rosmarinic acid (RA) in Salvia castanea Diels f. Tomentosa Stib (SCT) gives them significant potential for development as therapeutic agents for ischemic stroke (IS). However, the extraction process and quality of the active ingredients from SCT are still big challenges, with present processes providing insufficient pharmacological effects. This study aims to identify the optimal extraction process and perform a quality characterization of the total tanshinones and phenolic acids extracted from SCT, as well as to elucidate the neuroprotective effect of these extracts. Methods: The extraction process was optimized using an orthogonal experimental design (OED), and quality characterization was performed using HPLC, UV, and LC-MS. The neuroprotective effect of the extracted tanshinones and phenolic acids was studied using the middle cerebral artery occlusion (MCAO) paradigm, and its underlying mechanism was revealed through RNA-seq analysis combined with network pharmacology. Results: The optimal extraction pressure of total tanshinones was 60 MPa, while the extraction temperature and time for total phenolic acids were 4 °C and 25 min, respectively. In these extracts, the total tanshinone and phenolic acid contents increased to 369.43 and 189.10 mg/g, respectively; 23 of the 19 tanshinones and 23 phenolic acids identified in this study have not been observed in previous studies. It was demonstrated that the combined extract had a promising neuroprotective effect against IS; RNA-seq combined with network pharmacology analysis indicated that the active compounds may regulate a series of core genes associated with signaling pathways to protect against IS. Conclusions: The combined SCT extract studied in this research exerted neuroprotective effects on IS. In general, these findings improve our preliminary understanding of the chemical composition and bioactivity of SCT.

Stroke is the leading cause of mortality and morbidity worldwide, significantly impacting human welfare and overall health. Myeloperoxidase (MPO), a heme peroxidase secreted by neutrophils, plays a crucial role in the body's defense mechanisms, exhibiting pro-inflammatory and pro-oxidative properties. Additionally, MPO compromises the structural integrity and functional capacity of blood vessels, potentially leading to the formation and dislodgement of atherosclerotic plaques, vascular stenosis, thrombosis, and ultimately contributing to stroke occurrence. Following a stroke, a significant influx of neutrophils infiltrates the cerebral tissue, leading to an excessive release of MPO-derived oxidants and the subsequent promotion of various inflammatory mediators, thereby exacerbating cerebral tissue damage. Numerous studies have consistently demonstrated the pivotal role of MPO in the pathogenesis and progression of stroke, establishing it as a reliable prognostic indicator. Exploring the association between MPO and stroke enhances our understanding of the pathological mechanisms underlying stroke and aids in the development of therapeutic interventions. This review provides a comprehensive analysis of the molecular structure and cellular localization of MPO, elucidating its critical role in mediating vascular injury, the formation of Neutrophil Extracellular Traps (NETs), oxidative stress, neuroinflammation, disruption of the blood-brain barrier (BBB), and neuronal apoptosis during stroke pathogenesis. Additionally, we discuss recent advancements in MPO-targeted drugs and Traditional Chinese Medicine compounds as potential therapeutic strategies for stroke treatment.

Cerebral infarction is a predominant cause of global disability and mortality, characterized by pathogenesis that includes vascular stenosis, thrombosis, ischemic necrosis, and neuroinflammation. Despite progress in medical science, effective treatments for cerebral infarction are still constrained, prompting the investigation of alternative therapeutic strategies.

The objective of this review is to assess the efficacy of Traditional Chinese Medicine (TCM) as a treatment for cerebral infarction, emphasizing its mechanisms of action, effectiveness, and clinical relevance.

An extensive review of the existing literature regarding the role of TCM in the management of cerebral infarction, encompassing investigations on specific remedies, Chinese medicinal formulations, and contemporary advancements in preparation methodologies.

This review analyzes diverse TCM remedies recognized for their antioxidant, anti-inflammatory, and neuroprotective properties. Furthermore, it examines the synergistic effects of Chinese medicine formulations in modulating inflammation, enhancing blood circulation, and facilitating neural repair. Contemporary technological advancements that improve the accuracy and efficacy of Chinese medicine are also taken into account.

TCM has shown considerable promise in tackling the complex aspects of cerebral infarction. Specific remedies and formulations have demonstrated potential in modulating inflammatory responses, enhancing cerebral blood flow, and promoting neural repair mechanisms. Contemporary formulations have enhanced these effects, facilitating more precise and effective treatment.

While TCM presents a promising multi-faceted and multi-tiered strategy for addressing cerebral infarction, obstacles such as elucidating mechanisms and achieving standardization must be addressed. Continued research and clinical trials are crucial to fully exploit the therapeutic potential of TCM in the management of cerebral infarction.

This updated systematic review and meta-analysis aimed to re-evaluate the potential impact of body mass index (BMI) on the risk of recurrent stroke among stroke survivors.

We systematically searched PubMed, EMBASE, and Cochrane CENTRAL databases for studies published up to January 20, 2025. Eligible studies included randomized controlled trials, cohort studies, or case-control studies enrolling adult stroke or transient ischemic attack (TIA) survivors, with at least one year of follow-up, and reporting stroke recurrence by BMI categories. Studies were required to define stroke using clinical diagnosis or the International Classification of Disease (ICD) codes, and to categorize BMI using the World Health Organization (WHO) or Asia-Pacific classifications. The primary outcome was recurrent stroke risk between individuals with and without obesity, assessed using risk ratios (RRs). Secondary outcomes evaluated recurrent stroke risk across WHO BMI categories using adjusted hazard ratios (HRs). (PROSPERO: CRD42024580168) RESULTS: Fourteen studies (136,581 subjects) were included in the qualitative review (systematic review). Two using Asia-Pacific criteria were excluded, leaving 12 studies using WHO-classified BMI for quantitative synthesis (meta-analysis). Meta-analysis showed no significant difference in stroke recurrence between individuals with and without obesity (RR = 0.89, 95 % CI: 0.71-1.13). Meta-analysis of adjusted HRs showed no significant difference in stroke recurrence risk for individuals with underweight or overweight compared to those with normal weight. However, in the subgroup with ≥ 3 years follow-up, overweight was significantly associated with lower recurrent stroke risk (HR = 0.91). Also, individuals with obesity had a significantly lower stroke recurrence risk than normal weight individuals (HR = 0.85), particularly among those aged ≥ 65 years (HR = 0.82).

Overweight and obesity may be associated with a lower risk of stroke recurrence, particularly in older adults and during long-term follow-up (≥ 3 years). These findings suggest a potential obesity paradox in stroke survivors, warranting further investigations.

The Executive Function Performance Test (EFPT) is a performance-based test designed to assess parameters of executive function in instrumental activities of daily living. This study aimed to examine the validity and reliability of the Turkish EFPT in people with stroke. The present study was carried out on 72 individuals with stroke (32 female, 40 male) undergoing inpatient care at Etlik City Hospital. Analyses of internal consistency, inter-rater reliability, and convergent and divergent validity were carried out. The mean age of the participants was 62.81 ± 12.33 years and the mean time since stroke was 19.96 ± 39.81 months. According to the reliability analysis, the Cronbach's alpha level of the Turkish EFPT was found to be excellent (0.92). The inter-rater reliability analysis showed a very good agreement (0.99). A significant and high correlation was found between the MMSE (r = -0.732; p < .001) and Turkish EFPT in convergent validity analysis. In divergent validity analysis, significant but weaker correlations were found between the Turkish EFPT and the FIM (r = -0.499; p < .001) and SIS (r = -0.381; p < .031). This study may provide preliminary evidence for the validity and reliability of the Turkish EFPT in individuals with stroke. The EFPT appears to be able to facilitate effective assessment of executive function in stroke rehabilitation, to help determine the level of assistance required for functional activities, and to assist in planning suitable interventions.

Retinoic acid (RA), a vitamin A derivative, has been shown to prevent the development of neurological disorders by ensuring the integrity of the physiological structure of the neurovascular unit and regulating the physiological cell's function. After an ischemia event, RA reduces the effects of blood-brain barrier disruption by blocking the apoptotic signaling pathway. However, the effect of RA on smooth muscle cells (SMCs), which are crucial to maintaining blood perfusion, has never been investigated. This study aimed to evaluate the effect of RA on the vasoactive response of middle cerebral artery SMCs in normal and ischemic contexts (O2 and glucose deprivation, OGD). For this purpose, SMCs cultures were incubated with RA, and the vasoactive response was evaluated in both conditions (OGD and non-OGD). To simulate OGD, co-cultures of neurons and astrocytes were made and incubated with RA to analyze the effect of the secretome released by these cells on SMCs contractility. In non-OGD conditions, RA induced rapid relaxation of SMCs and, in the long term (24 h), promoted cell contraction. In OGD conditions, SMCs contractility patterns were different when pre-incubated with RA. In these conditions, NA loses its contractility effect, and SNP seems to revert its relaxant effect. However, SMCs pre-incubated with 5 uM RA show the vasorelaxant pattern typical of SNP, despite the OGD condition. These effects demonstrate an effect of RA on the vasoactive profile of SMCs, with therapeutic potential in OGD conditions.

Split-belt treadmill training (SBTT) enhances gait symmetry in patients with stroke (PwS) by improving sensorimotor adaptation, However, it remains unclear whether repeated SBTT leads to long-term acquisition of gait adaptation skills and whether it improves functional walking in PwS. This study aimed to investigate the effect of SBTT on gait symmetry and lower limb function in PwS. We designed a parallel-group randomized controlled experiment. PwS who have the ability to stand and walk unassisted for at least 30 min were included in this study. They were randomly assigned to either rehabilitation with SBTT or with tied-belt treadmill training (TBTT). The treatment was provided once per day, five times per week for four weeks(total of 20 treatments). Gait analysis including step length, gait speed, temporal and spatial asymmetry and clinical assessment of lower limb function using Fugl-Meyer Assessment - lower extremity (LEFM), the Berg Balance Scale (BBS), the Wisconsin Gait Scale(WGS), and the Timed Up and Go Test (TUGT) were measured at baseline, 2 weeks post intervention, 4 weeks post intervention, and at follow-up after 4 weeks finishing the exercise. Two-way repeated measures ANOVA was used for intergroup comparisons between the two groups at different time points. In addition, Pearson correlation analysis was used to test the relationship between the improvement of clinical assessment scales and changes in gait parameters. Results showed that SBTT could effectively and efficiently improve the spatial asymmetry and speed of gait, as well as lower limb balance and walking function in PwS. In addition, the improvement of functional walking was positively correlated with the decrease of spatial asymmetry, and the increase of step length of paretic leg. In Conclusion, a 4-week SBTT intervention could effectively improve gait asymmetry and, consequently, enhance walking and lower limb function in PwS with independent walking ability.

Researchers have increasingly focused on the efficacy of acupuncture therapy (AT) combine with rehabilitation therapy (RT) for post-stroke urinary incontinence (PSUI). This study aims to fully assess the efficacy of AT plus related RT in treating PSUI.

We systematically searched eight databases from their inception to March 2025 for randomized controlled trials (RCTs) evaluating AT plus related RT for PSUI. Stata 18.0 was utilized for the meta-analyses.

Thirty-six studies involving 2,796 subjects were included, with AT plus related RT performed in the treatment group. The total effective rate of AT plus RT was significantly higher than that of RT or AT alone [RR = 1.23, 95% CI (1.19, 1.28), p < 0.001]. AT plus RT was also superior to related RT or related AT in improving maximum bladder capacity [WMD = 44.93, 95% CI (32.00, 57.87), p < 0.001]; increasing maximum urinary flow rate [WMD = 2.64, 95% CI (1.27, 4.01), p < 0.001], mean urine output per time [WMD = 44.30, 95% CI (20.31, 68.29), p < 0.001], and pelvic floor muscle strength (including fast [WMD = 2.64, 95% CI (1.04, 4.25), p = 0.001], slow [WMD = 6.09, 95% CI (3.44, 8.75), p < 0.001], and complex muscle fibers [WMD = 5.46, 95% CI (3.60, 7.32), p < 0.001]); and reducing the residual urine volume [WMD = -20.84, 95% CI (-27.53, -14.14), p = 0.001], maximal detrusor pressure [WMD = -10.6, 95% CI (-12.72, -8.55), p = 0.001], frequency of 24-h UI [WMD = -1.40, 95% CI (-1.92, -0.88), p < 0.001], and frequency of 24-h urination [WMD = -3.76, 95% CI (-4.87, -2.66), p < 0.001]. Moreover, AT plus RT significantly reduced scores on the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) [WMD = -2.40, 95% CI (-2.93, -1.83), p < 0.001]. While reductions were also observed in the quality of life (QOL) score [WMD = -0.72, 95% CI (-1.64, 0.20), p = 0.127] and the National Institutes of Health Stroke Scale (NIHSS) score [WMD = -3.51, 95% CI (-8.20, 1.18), p = 0.143], these did not reach statistical significance. Additionally, AT plus RT significantly increased the Incontinence Quality of Life Scale (I-QOL) score [WMD = 11.71, 95% CI (8.10, 15.33), p < 0.001] and the Barthel index (BI) score [WMD = 6.92, 95% CI (-0.22, 14.05), p = 0.058].

AT plus RT outperforms related RT or related AT in improving clinical efficacy and bladder function in PSUI patients. However, the number of included studies on AT plus RT remains limited, highlighting the need for more high-quality RCTs are needed to validate the findings.

https://www.crd.york.ac.uk/prospero/, identifier [CRD42024588520].

Stroke remains a leading cause of disability and mortality worldwide, primarily due to the complex and multifaceted nature of its pathophysiology. This review aims to provide a comprehensive and mechanistic understanding of the crosstalk between key signaling pathways activated during stroke and the therapeutic potential of specific receptors: PPAR-γ, ROCK, CB1R, and CB2R. We delve into the intricate signaling cascades that occur post-stroke, including excitotoxicity, oxidative stress, and inflammation, highlighting the pivotal molecular players involved. PPAR-γ, known for its neuroprotective and anti-inflammatory properties, emerges as a critical modulator in stroke therapy. ROCK, a central component in the Rho/ROCK pathway, is implicated in vascular and neuronal damage, making its inhibition a promising therapeutic strategy. The roles of CB1R and CB2R within the endocannabinoid system are explored, with a focus on their dualistic nature in neuroprotection and neurotoxicity. The review further examines the interconnectivity of these receptors within the stroke signaling network, proposing that their synergistic modulation could enhance therapeutic outcomes. Current therapeutic approaches, including pharmacological and multi-target strategies, are critically evaluated, addressing the challenges in translating mechanistic insights into clinical practice. Additionally, the identification and utilization of biomarkers for stroke diagnosis and therapy monitoring are discussed, offering a glimpse into future prospects. Emerging therapies, novel drug developments, and personalized medicine approaches are presented as potential game-changers in stroke treatment.

Observational studies have indicated an association between systemic lupus erythematosus (SLE) and stroke. However, the genetic causality of this association remains incompletely understood. This study utilizes Mendelian randomization (MR) to investigate the potential causal relationship between SLE and the risk of stroke.

We utilized summary-level statistics data from the largest genome-wide association studies (GWASs) on SLE and stroke. The primary MR analysis was conducted using the inverse variance weighted (IVW) method, with supplementary analyses performed using the MR-Egger and weighted median (WM) methods. Sensitivity and heterogeneity analyses were additionally performed to ensure the robustness of the results.

The IVW analysis indicated a potential causal relationship between SLE and an increased risk of any ischemic stroke (odds ratio [OR] = 1.039, 95% confidence interval [CI]: 1.014-1.066, p = 0.002). However, no significant genetic association was observed between SLE and large artery stroke (OR: 1.024, 95% CI: 0.975-1.076, p = 0.326), cardioembolic stroke (OR: 1.014, 95% CI: 0.948-1.085, p = 0.667), small vessel stroke (OR: 0.983, 95% CI: 0.942-1.026, p = 0.458), or intracerebral hemorrhage (OR: 0.992, 95% CI: 0.934-1.054, p = 0.804).

This MR study provides genetic evidence supporting a causal association between SLE and an increased risk of ischemic stroke. These findings underscore the significance of active monitoring and prevention of ischemic stroke to mitigate cerebrovascular comorbidities in SLE patients. Given the existence of ethnic-specific genomic heterogeneity, caution is warranted in interpreting these results.

Ischemic stroke (IS) is caused by temporary or permanent obstruction of the brain's blood supply. The disruption in glucose and oxygen delivery that results from the drop in blood flow impairs energy metabolism. A significant pathological feature of IS impaired energy metabolism. Astrocytes, as the most prevalent glial cells in the brain, sit in between neurons and the microvasculature. By taking advantage of their special anatomical location, they play a crucial part in regulating cerebral blood flow (CBF) and metabolism. Astrocytes can withstand hypoxic and ischemic conditions better than neurons do. Additionally, astrocytes are essential for maintaining the metabolism and function of neurons. Therefore, the "neurocentric" perspective on neuroenergetics is gradually giving way to a more comprehensive perspective that takes into account metabolic interaction between astrocytes and neurons. Since neurons in the core region of the infarct are unable to undergo oxidative metabolism, the focus of attention in this review is on neurons in the peri-infarct region. We'll go over the metabolic crosstalk of astrocytes and neurons during the acute phase of IS using three different types of metabolites: lactate, fatty acids (FAs), and amino acids, as well as the mitochondria. After IS, astrocytes in the peri-infarct zone can produce lactate, ketone bodies (KBs), glutamine (Gln), and l-serine, shuttling these metabolites, along with mitochondria, to neurons. This process helps maintain the energy requirements of neurons, preserves their redox state, and regulates neurotransmitter receptor activity.

Ischemic stroke represents one of the leading cerebrovascular diseases with a high rate of mortality and disability globally. To date, there are no effective clinical drugs available to improve long-term outcomes for post-stroke patients. A novel nucleic acid agent circSCMH1 which can promote sensorimotor function recovery in rodent and nonhuman primate animal stroke models has been found. However, there are still delivery challenges to overcome for its clinical implementation. Besides, its effects on post-stroke cognitive functions remain unexplored. Herein, lipid nanoparticle circSCMH1@LNP1 is established to deliver circSCMH1 and explore its therapeutic efficacy comprehensively. Distribution experiments demonstrate that intranasal administration of circSCMH1@LNP1 significantly increases circSCMH1 distribution in the peri-infarct region and reduces its non-specific accumulation in other organs compared to intravenous injection. Therapeutic results indicate that circSCMH1@LNP1 promotes synaptic plasticity, vascular repair, neuroinflammation relief, and myelin sheath formation, thereby achieving enhanced sensorimotor and cognitive function recovery in post-stroke mice. In conclusion, this research presents a simple and effective LNP system for efficient delivery of circSCMH1 via intranasal administration to repair post-stroke brain injury. It is envisioned that this study may bridge a crucial gap between basic research and translational application, paving the way for clinical implementation of novel circSCMH1 in post-stroke patient management.

In practical clinical scenarios, improved diagnostic methods have been developed for the precise visualization of molecular targets using molecular imaging in brain diseases. Recently, the introduction of innovative molecular imaging modalities across both macroscopic and mesoscopic dimensions, with remarkable specificity and spatial resolution, has expanded the scope of applications beyond diagnostic testing, with the potential to guide therapeutic interventions, offering real-time feedback in the context of brain therapy. The molecular imaging-guided integration of diagnosis and treatment holds the potential to revolutionize disease management by enabling the real-time monitoring of treatment responses and therapy adjustments. Given the vibrant and ever-evolving nature of this field, this review provides an integrated picture on molecular image-guided diagnosis and treatment integration for brain diseases involving the basic concepts, significant breakthroughs, and recent trends. In addition, based on the current achievements, some critical challenges are also discussed.

Stroke is a severe disease characterized by the obstruction of blood vessels in the central nervous system. An essential therapeutic strategy for ischemic stroke is strengthening angiogenesis, which effectively promotes the long-term recovery of neurological function. Therefore, it is critical to explore and develop new drugs that promote angiogenesis after ischemic stroke. Kaempferol has been employed to treat ischemic diseases; However, its proangiogenic effects in ischemic stroke remain unclear. In the study, we explored the long-term therapeutic effects and mechanisms of kaempferol on ischemic stroke in vivo and in vitro. A rat model of autologous thrombus stroke and oxygen-glucose deprivation (OGD)-induced human brain microvascular endothelial cells (HBMECs) model was established to assess the effects of kaempferol in vivo (50 mg/kg/d, ig, 14 d) and in vitro (0.1, 0.3, 1 μmol L-1). The results showed that long-term administration of kaempferol ameliorated neurological deficits and infarct volume in ischemic stroke rats. In addition, kaempferol relieved vascular embolization; enhanced microvascular endothelial cell survival, proliferation, migration, and lumen formation; increased the density of microvessels in the peri-infarct cortex; and promoted neovascular structure remodeling by increasing the coverage of astrocyte end-feet and expression of tight-junction proteins (TJPs). Further analysis revealed that the HIF-1α/VEGF-A/Notch1 signaling pathway was activated by kaempferol, and that inhibition of Notch1 blocked kaempferol-induced angiogenesis. Taken together, our results indicate that kaempferol exerts neuroprotective effects by stimulating endogenous angiogenesis and neovascular structural remodeling via the HIF-1α/VEGF-A/Notch1 signaling pathway, suggesting the therapeutic potential of kaempferol in ischemic stroke.

Ischaemic stroke is the most prevalent stroke subtype, accounting for 80-90% of all cases worldwide, and remains a leading cause of morbidity and mortality. Its pathophysiology involves complex molecular cascades, with oxidative stress playing a central role. During cerebral ischaemia, reduced blood flow deprives neurons of essential oxygen and nutrients, triggering excitotoxicity, mitochondrial dysfunction, and excessive production of reactive oxygen and nitrogen species (RONS). Not only do these species damage cellular components, but they also activate inflammatory pathways, particularly those mediated by the transcription factor nuclear factor kappa-B (NF-κB). The pro-inflammatory milieu intensifies neuronal damage, compromises blood-brain barrier integrity, and exacerbates reperfusion-induced damage. Recent findings highlight the importance of the gut microbiota in modulating stroke outcomes, primarily through metabolic and immunological interactions along the gut-brain axis. Dysbiosis, characterised by reduced microbial diversity and an imbalance between beneficial and harmful strains, has been linked to increased systemic inflammation, oxidative stress, and worse prognoses. Specific gut-derived metabolites, including short-chain fatty acids (SCFAs) and trimethylamine N-oxide (TMAO), appear to either mitigate or intensify neuronal injury. SCFAs may strengthen the blood-brain barrier and temper inflammatory responses, whereas elevated TMAO levels may increase thrombotic risk. This narrative review consolidates both experimental and clinical data demonstrating the central role of oxidative stress in ischaemic stroke pathophysiology and explores the gut microbiota's ability to modulate these damaging processes. Therapeutic strategies targeting oxidative pathways or rebalancing gut microbial composition, such as antioxidant supplementation, dietary modulation, probiotics, and faecal microbiota transplantation, present promising paradigms for stroke intervention. However, their widespread clinical implementation is hindered by a lack of large-scale, randomised trials. Future efforts should employ a multidisciplinary approach to elucidate the intricate mechanisms linking oxidative stress and gut dysbiosis to ischaemic stroke, thereby paving the way for novel, mechanism-based therapies for improved patient outcomes.

The incidence of stroke-related restless legs syndrome (RLS) has been reported to be high but varies regionally. Therefore, this study aimed to investigate the incidence and some of the factors related to restless legs syndrome after stroke onset in patients in Vietnam.

Data were collected from a total of 423 patients who had stroke, including 283 ischemic and 140 hemorrhagic strokes, which were confirmed by magnetic resonance imaging within 7 days after the onset of symptoms, at the Department of Stroke, Military Hospital 103 from September 2023 to April 2024. Restless legs syndrome was diagnosed 1 month after the stroke onset according to the criteria of the International Restless Legs Syndrome Study Group.

Restless legs syndrome was diagnosed in 59 patients (11.6%), including 37 (13.1%) who had ischemic stroke and 12 (8.6%) who had hemorrhagic stroke. An increased rate of restless legs syndrome was observed in stroke patients with brain lesions in the thalamus and lentiform nucleus; those who smoked; and those with a family history of restless legs syndrome.

This study found that the incidence of restless legs syndrome after stroke was 11.6% overall and 13.1% and 8.6% after ischemic and hemorrhagic strokes, respectively. Lesion in the thalamus and lentiform nucleus, smoking history, and family history of restless legs syndrome were the predictors of restless legs syndrome after stroke onset.

Hemorrhagic stroke is a debilitating neurological disease, affecting millions worldwide. Characterized by bleeding in the brain, it is caused by a breakdown of the blood-brain barrier (BBB) and causes damage through the presence of iron in the brain, immune activation and increased intracranial pressure. The goal of this mini-review is to explore the signaling pathways that lead to cell death that are a part of disease progression in hemorrhagic stroke. This mini-review will highlight clinical observations and data, while also incorporating findings using preclinical disease models. There are important roles for apoptosis, necroptosis, necrosis, autophagy, ferroptosis, and pyroptosis in hemorrhagic stroke. Recent work has highlighted the interplay between these phenomena, providing key regulators as potential therapeutic targets, including reactive oxygen species, iron metabolism, and caspases. Therapeutic strategies that can delay or counteract the cytotoxic effects of hemorrhage can improve clinical outcomes in hemorrhagic stroke patients.

Hemorrhagic stroke is associated with significant morbidity and mortality, prompting the search for modifiable risk factors and prognostic indicators. Elevated homocysteine levels have been implicated in vascular diseases, but their link to hemorrhagic stroke outcomes remains unclear. This systematic review and meta-analysis aimed to evaluate the association between homocysteine levels and outcomes in hemorrhagic stroke patients.

The MEDLINE, EMBASE, and Cochrane Central databases were searched for studies comparing the outcomes of hemorrhagic stroke in patients with high versus normal homocysteine levels. Data were pooled using random-effects models to calculate odds ratios (ORs) for mortality and poor functional outcomes and standardized mean differences (SMDs) for homocysteine levels, with respective 95% confidence intervals (CIs).

The review included 10 studies. Pooled analysis showed no significant association between high homocysteine levels and increased risk of mortality (OR: 1.123, 95% CI: 0.589 to 2.143), poor functional outcomes (OR: 1.203, 95% CI: 0.962 to 1.504), or unfavorable neurological outcomes (OR: 1.001, 95% CI: 0.618 to 1.620). Substantial heterogeneity was observed among studies.

High homocysteine levels were not significantly associated with mortality, functional outcomes, or unfavorable neurological outcomes in hemorrhagic stroke patients. The clinical utility of homocysteine as a prognostic marker in this population remains uncertain and warrants further research.

https://www.crd.york.ac.uk/PROSPERO/, CRD42024527207.

Ischemic stroke is a leading cause of death and disability worldwide. Therefore, there is a critical need to explore the underlying mechanisms and develop effective treatment strategies for ischemic stroke. As small and non-immunogenic nucleic acid molecules, aptamers can be easily chemically modified, break through the blood-brain barrier, and be screened using the classic Systematic Evolution of Ligands by Exponential Enrichment. With the advancements in emerging technologies, aptamer-based strategies have provided diagnostic and therapeutic potential for applications in central nervous system diseases. Aptamers have become a useful tool for targeted therapy and biomarker discovery in ischemic stroke. This review presents recent advances and perspectives on aptamer applications in stroke prevention, treatment, and diagnosis, focusing on targeting pathological blood clotting or thrombosis, inflammatory responses, and specific biomarkers in key cells.

This study aimed to investigate the effectiveness of the Gugging Swallowing Screen (GUSS) in swallowing disorder screening of patients with poststroke and assess its adoption value in dietary management.

Swallowing function in 174 patients with poststroke was screened using the GUSS scale and the water swallow test (WST). Patients with swallowing disorders were randomly assigned to the observation group (OG) and the control group (CG). The CG received standard treatment and care, while the OG also underwent GUSS-based swallowing function assessment and a graded dietary management plan. The effectiveness of improvements in swallowing function, psychological health assessments, and the incidence of complications was compared.

The effect sizes (ES) and standardized response mean (SRM) of GUSS scale were markedly superior to those of WST (p < 0.05). OG exhibited a markedly higher rate of improvement in swallowing function versus CG (p < 0.05). Adverse events were markedly less frequent in OG versus CG (p < 0.05). Alb, PA, and TNF in OG were superior to those in CG after treatment (p < 0.05). The psychological function, physical function, social function, material life status scores, and overall quality of life (QoL) evaluation questionnaire scores of OG patients were superior to those in CG at discharge (p < 0.05). The incidence of adverse reactions in OG was substantially inferior to that in CG (p < 0.05).

GUSS is an effective screening tool for identifying swallowing disorders in patients with poststroke. Swallowing dysfunction severity-based tailoring dietary management plans can markedly improve patients' swallowing function and lower the risk of swallowing-related complications.

Convincing evidence has indicated that geniposide possesses neuroprotective effects in ischemic stroke. This study is designed to explore the potential molecular mechanism of geniposide in oxygen-glucose deprivation/reoxygenation (OGD/R)-treated BV-2 microglial cells and middle cerebral artery occlusion (MCAO) mice. OGD/R model in BV2 microglial cells was established in this research. Cell viability and apoptosis were determined using Cell Counting Kit-8 (CCK-8) and flow cytometry assays. Protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), microtubule-associated protein light chain 3 (LC3)-II/LC3-I, Beclin-1, inducible nitric oxide synthase (iNOS), CD86, sex determining region Y-box 2 (SOX2), receptor-interacting serine/threonine-protein kinase 1 (RIPK1), TNF-α, IL-1β, ARG1, and CD163 were detected by western blot assay. RIPK1 mRNA level was determined using real-time quantitative polymerase chain reaction (RT-qPCR). TNF-α and IL-1β levels were analyzed using ELISA kits. After JASPAR analysis, binding between SOX2 and RIPK1 promoter was predicted and verified using chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. The effects of geniposide on cerebral ischemic injury were assessed using MCAO mice in vivo. Geniposide treatment relieved OGD/R-triggered BV-2 cell viability promotion and apoptosis, autophagy, inflammatory response, and M1 polarization inhibition in vitro. SOX2 and RIPK1 expression was decreased in OGD/R-treated BV-2 cells. In mechanism, SOX2 upregulated RIPK1 transcription by binding to the RIPK1 promoter region. Geniposide administration significantly alleviated cerebral ischemic injury in MCAO mice in vivo. Geniposide administration protects against cerebral ischemic injury through regulating the SOX2/RIPK1 axis, providing a potential direction for the application of geniposide in the treatment of ischemic stroke.

This review proposes an innovative closed-loop rehabilitation strategy that integrates multiple subdomains of stroke science to address the global challenge of upper-limb dyskinesia post-stroke. Despite advancements in neural remodeling and rehabilitation research, the compartmentalization of subdomains has limited the effectiveness of current rehabilitation strategies. Our approach unites key areas-including the post-stroke brain, upper-limb rehabilitation robotics, motion sensing, metrics, neural microfluidics, and neuroelectronics-into a cohesive framework designed to enhance upper-limb motion rehabilitation outcomes. By leveraging cutting-edge technologies such as lightweight rehabilitation robotics, advanced motion sensing, and neural microfluidic models, this strategy enables real-time monitoring, adaptive interventions, and personalized rehabilitation plans. Furthermore, we explore the potential of closed-loop systems to drive neural plasticity and functional recovery, offering a transformative perspective on stroke rehabilitation. Finally, we discuss future directions, emphasizing the integration of emerging technologies and interdisciplinary collaboration to advance the field. This review highlights the promise of closed-loop strategies in achieving unprecedented integration of subdomains and improving post-stroke upper-limb rehabilitation outcomes.

Stroke is one of the most common causes of disability and death worldwide. With the rapidly growing stroke survivor population, it is crucial to identify an effective method for their healthcare. Recovery from stroke is followed by physiotherapy to promote rehabilitation. Task-oriented circuit training is designed to improve stroke patients' overall functioning during rehabilitation. This research aims to assess the effectiveness of task-oriented circuit training compared with conventional physiotherapy. The investigators have planned an 8-week parallel, two-arm, prospective, randomised clinical study. Participants will be enrolled from eight branches of the centre for the rehabilitation of the paralysed (CRP). We have planned to recruit 506 stroke survivors via a 1:1 random assignment procedure for 24 months. As a main objective, the Action Arm Research Test and the Timed Up and Go will be used to test upper and lower limb motor function. The secondary objectives will include daily living and balance activities, which will be evaluated using the Barthel Index and the Berg Balance Scale. The post-test and follow-up data will be collected after 8 and 12 weeks. The final analysis will include dropouts and treatment side effects. This study has been granted ethical approval by the Ethics Review Committee of the CRP (CRP-R&E-0401-357)). All activities and interventions will be carried out following the Helsinki Declaration of 2020. The findings will be published in peer-reviewed journals and disseminated at international conferences. Trial registration number: CTRI/2023/09/057907 (21 September 2023) (Prospectively registered).

Virtual reality (VR) is a rapidly developing technology that has gained significant traction in the treatment and rehabilitation of individuals with stroke. Research on VR-based stroke treatment has garnered increasing attention.

The aim of this study is to present a bibliometric analysis of VR for stroke studies to identify the application status, research hotspots, and emerging trends and guide future scientific research.

We included studies and reviews on the topic of VR-based stroke treatment and rehabilitation from 1999 to 2023 were retrieved from Web of Science Core Collection database. Citespace 6.3.1 and VOSviewer 1.6.20 software was used for the visual analysis of publications, institutions, authors, journals, citations, and Scimago Graphica software was used for the geographic visualization of published countries or regions.

Our study analyzed 1171 papers on VR-based stroke rehabilitation published between 1999 and 2023, revealing a gradual increase in annual publications over the past 2 decades, peaking at 154 in 2022. North America and Western Europe were identified as major contributors, with significant input from their institutions, researchers, and publications. The Journal of NeuroEngineering and Rehabilitation emerged as the leading journal in this field, while Calabrò Rocco Salvatore was recognized as the most prolific author, focusing on the neurophysiological impacts of VR on patients with stroke. Keywords with notable citation bursts, such as "environment," "trial," "arm," and "motor learning," highlighted the core research themes in this domain.

Our study provides valuable insights into the current research hotspots and emerging trends in VR-based stroke treatment and rehabilitation. Current research primarily focuses on evaluating the effectiveness of VR in improving upper limb function and balance in patients with stroke. Future directions are shifting towards integrating VR with rehabilitation techniques, such as physiotherapy and occupational therapy, while advancements in VR technology continue to garner increasing attention.

There is a desperate need for precise nanomedications to treat ischemic cerebral injury. Yet, the drawbacks of poor delivery efficiency and off-target toxicity in pathologic parenchyma for traditional antioxidants against ischemic stroke result in inadequate brain accumulation. M13 bacteriophages are highly phagocytosed by M1-polarized microglia and can be carried toward the neuroinflammatory sites. Here, a bio-active, inhalable, Ce0.9Zr0.1O2-backpacked-M13 phage (abbreviated as CZM) is developed and demonstrates how M13 bacteriophages are taken up by different phenotypes' microglia. With the M1 microglia's proliferating and migrating, CZM can be extensively and specifically delivered to the site of the ischemic core and penumbra, where the surviving nerve cells need to be shielded from secondary oxidative stress and inflammatory cascade initiated by reactive oxygen species (ROS). With non-invasive administration, CZM effectively alleviates oxidative damage and apoptosis of neurons by eliminating ROS generated by hyperactive M1-polarized microglia. Here, a secure and effective strategy for the targeted therapy of neuroinflammatory maladies is offered by this research.

Ischemic stroke (IS) continues to be a major public health concern and is characterized by significantly high mortality and disabling rates. Inhibiting nerve cells death and enhancing the repair of ischemic tissue are important treatment concepts for IS. Currently, the mainstream treatment strategies mainly focus on short-term care, which underscores the urgent need for novel therapeutic strategies for long-term care. Emerging data reveal that flavonoids have surfaced as promising candidates for IS patients' long-term care. Flavonoids can alleviate neuroinflammation and anti-apoptosis due to their characteristic pharmacological mechanisms. Clinical evidence suggests that long-term flavonoids intake improves IS patients' long-term outcomes. Though the effect of flavonoids in IS treatment has been explored for decades, the neuroprotective pharmacodynamics have not been well established. Thereby, the aim of current review is to summarize the pathways involved in neuroprotective effect of flavonoids. This review will also advance the potential of flavonoids as a viable clinical candidate for the treatment of IS.

Ischemic stroke's complex pathophysiology demands therapeutic approaches targeting multiple pathways simultaneously, yet current treatments remain limited. We developed an innovative drug discovery pipeline combining a deep learning approach with experimental validation to identify natural compounds with comprehensive neuroprotective properties. Our computational framework integrated SELFormer, a transformer-based deep learning model, and multiple deep learning algorithms to predict NC bioactivity against seven crucial stroke-related targets (ACE, GLA, MMP9, NPFFR2, PDE4D, and eNOS). The pipeline encompassed IC50 predictions, clustering analysis, quantitative structure-activity relationship (QSAR) modeling, and uniform manifold approximation and projection (UMAP)-based bioactivity profiling followed by molecular docking studies and experimental validation. Analysis revealed six distinct NC clusters with unique molecular signatures. UMAP projection identified 11 medium-activity (6 < pIC50 ≤ 7) and 57 high-activity (pIC50 > 7) compounds, with molecular docking confirming strong correlations between binding energies and predicted pIC50 values. In vitro studies using NGF-differentiated PC12 cells under oxygen-glucose deprivation demonstrated significant neuroprotective effects of four high-activity compounds: feruloyl glucose, l-hydroxy-l-tryptophan, mulberrin, and ellagic acid. These compounds enhanced cell viability, reduced acetylcholinesterase activity and lipid peroxidation, suppressed TNF-α expression, and upregulated BDNF mRNA levels. Notably, mulberrin and ellagic acid showed superior efficacy in modulating oxidative stress, inflammation, and neurotrophic signaling. This study establishes a robust deep learning-driven framework for identifying multitarget natural therapeutics for ischemic stroke. The validated compounds, particularly mulberrin and ellagic acid, are promising for stroke treatment development. Our findings demonstrate the effectiveness of integrating computational prediction with experimental validation in accelerating drug discovery for complex neurological disorders.

Stroke occurs when the blood flow to the brain is interrupted due to a rupture of blood vessels or blockage in the brain. It is the major cause of physical disabilities in adulthood. Despite advances in surgical and pharmacological therapy, functional recovery from stroke is limited, affecting quality of life. Stem cell therapy, which may treat neurological disorders associated with brain traumas, including stroke, is an important focus in stroke research and treatment. Stem cell therapy has primarily used a type of adult stem cells called mesenchymal stem cells (MSCs) due to their universality and ability to develop into multiple lineages to regenerate brain cells and repair brain tissues. A significant number of clinical studies provide evidence of the potential of MSCs to treat stroke. This review summarizes the therapeutic mechanism and applications of MSCs in stroke treatment. We also highlight the current challenges and future prospects of adult MSC therapy for stroke treatment.

Ischemic stroke is a prevalent form of cerebrovascular accident, with its pathogenesis involving the intricate interplay between neuroinflammation and energy metabolism. Cerebral ischemia disrupts oxygen and energy supply, triggering metabolic dysregulation and activating neuroinflammatory responses, ultimately resulting in cellular damage. This review provides an exhaustive analysis of the complex mechanisms of ischemic stroke, with a particular focus on the interaction between neuroinflammation and energy metabolism. The interruption of oxygen and energy supply due to cerebral ischemia initiates metabolic dysregulation and activates neuroinflammatory responses, including the release of inflammatory cytokines and the activation of immune cells, contributing to cellular damage and further metabolic disturbances. Studies indicate that dysregulation of energy metabolism significantly impairs neural cell function and interacts with neuroinflammation, exacerbating ischemic brain injury. Therapeutic strategies primarily concentrate on modulating energy metabolism and suppressing neuroinflammatory responses, emphasizing the importance of in-depth research into their interaction to provide a theoretical foundation for new treatment strategies for ischemic stroke. Future research should focus on how to balance anti-inflammatory treatment with energy regulation to minimize neural damage and promote recovery.

Stroke is a sudden neurological decline caused by cerebrovascular diseases or impaired blood circulation. Research investigating the connection between glycated hemoglobin A1c (HbA1c) levels and stroke severity is limited. This study examined the connection between HbA1c levels and stroke severity in patients with acute ischemic stroke. A retrospective cross-sectional analysis of the medical records of 1103 patients with acute ischemic stroke from January 2020 to January 2024 was conducted. Patients were divided into seven groups on the basis of their HbA1c levels. Stroke severity within these groups was assessed via the National Institutes of Health Stroke Scale (NIHSS), with the aim of identifying correlations between stroke severity and glycemic status. This study examined the impact of various HbA1c levels on a range of demographic and clinical characteristics in stroke patients. The patients were grouped into seven categories on the basis of their HbA1c levels, and characteristics such as age; body mass index (BMI); LDL, HDL, and creatinine levels; and NIHSS scores at hospital admission were compared across these groups. Significant differences were observed in age, LDL levels (F = 3.999, P < 0.001), and creatinine levels (F = 1.303, P = 0.253) among the HbA1c categories. However, there were no significant differences in BMI, HDL levels, or length of hospital stay. A positive correlation was found between HbA1c levels and NIHSS scores, indicating that higher HbA1c levels are associated with greater stroke severity. This study revealed that the risk of severe stroke increases significantly when HbA1c levels exceed 6.5%. In contrast, maintaining HbA1c levels below 6.5% is linked to a reduced risk of severe stroke and lower mortality. Additionally, older adults are at greater risk and tend to experience more severe strokes.

Amygdalin, a key component of Peach kernel (semen persicae), also known as Taoren, is a traditional Chinese herb known for promoting blood circulation and alleviating blood stasis, especially in stroke treatment. This study aimed to explore the effects of amygdalin on neurological function in a rat model of acute ischemic stroke.

We induced acute ischemic stroke in Sprague-Dawley rats by occluding the right middle cerebral artery (MCAO) for 30 min, followed by reperfusion. Amygdalin was administered intraperitoneally at doses of 5 mg, 10 mg, and 20 mg per kilogram starting 24 h post-reperfusion for three consecutive days. We assessed cerebral infarct volume and neurological function, and analyzed the brain tissue using western blotting.

Amygdalin significantly reduced cerebral infarct volume resulting from MCAO in the 5-mg group (amygdalin 5 mg/kg; 18.02 ± 7.51 %), 10-mg group (amygdalin 10 mg/kg; 16.25 % ± 6.35 %) and 20-mg group (amygdalin 20 mg/kg; 12.26 ± 6.69 %) compared to the sham group (phosphate buffer saline; 28.99 ± 6.36 %) (all p < 0.001). The 10-mg and 20-mg groups showed significantly lower modified neurological severity scores (mNSS) than the sham group 5 days post-reperfusion (p < 0.05, p < 0.0001, respectively). Performance on the rotarod test also improved significantly in the 10-mg group (p < 0.05) and 20-mg group (p < 0.0001) compared to the sham group, and the distance traveled in the open-field test increased significantly in the 5-mg group (p < 0.001), 10-mg group (p < 0.0001) and 20-mg group (p < 0.0001) compared to the sham group. Western blotting revealed that the expression of uncleaved caspase-3 in the cerebral cortex was greater in the sham group compared to the control (without MCAO and treatment) and the 20-mg groups (both p < 0.05), while the expression of caspase-9 was greater in the control and 20-mg groups than in the sham group (both p < 0.05).

Intraperitoneal administration of amygdalin for three days reduced cerebral infarct volume and improved neurological function in a rat model of acute ischemic stroke. Additionally, amygdalin decreased uncleaved caspase-3 expression and increased caspase-9 expression. The findings suggest that amygdalin plays a neuroprotective role through modulation of apoptosis process via the intrinsic pathway.

Multiple cerebral infarctions (MCIs) represent a common type of ischaemic stroke that affects or even endangers a patient's life. Qilong capsule (QLC), a Chinese patent medicine made from Buyang Huanwu Decoction (BYHWD) is suitable for treating the sequelae of ischaemic stroke, such as multi-infarct dementia (MID). However, its biological mechanism has not been fully explored.

The aim of this study was to explore the mechanism of QLC in treating MCI and its sequelae.

Male SD rats aged 7-8 weeks and weighing 210-230 g were used as an MCI model, and QLC was used as interventions. The neurobehavioural effects of QLC on MCI model rats were evaluated by observing body weight, neurological function score, and forelimb grip and water maze test results. The effects of QLC on neurons and microglia were observed via haematoxylin‒eosin (HE) staining, silver staining, transmission electron microscopy and positron emission tomography/computed tomography (PET/CT). The effects of QLC on platelets were observed via the platelet aggregation rate and flow cytometry (FCM). Finally, the mechanism of QLC was verified via ELISA, immunofluorescence staining and Western blotting.

These experiments showed that QLC improves neurobehavioural measures, forelimb grip strength, and spatial memory after MCI by ameliorating brain tissue and neuronal damage. QLC also effectively inhibited the inflammatory response after MCI. We also found that QLC can decrease microglia activation and reduce the expression of translocator protein 18 kDa (TSPO). QLC can improve platelet aggregation and reduce the expression of CD62p and CD61, indicating that QLC has a significant anti-platelet aggregation effect. At the molecular level, we found that QLC affects the content of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), reduces the expression of recombinant purinergic receptor P2Y, G protein coupled 12 (P2Y12) in microglia, and regulates the P2Y12/adenylate cyclase (AC)/cAMP signalling pathway.

QLC can ameliorate neuronal necrosis and MID induced by MCI and has an antiplatelet aggregation effect in rats. QLC may treat MID by regulating P2Y12/AC/cAMP.