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.

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.

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.

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are a potential off-the-shelf product for acute ischemic stroke. This study explored the underlying mechanism of Cytopeutics® hUC-MSCs (Neuroncell-EX) as well as its feasibility and efficacy at two different doses: 2 × 106 cells per rat and 4 × 106 cells/rat in middle cerebral artery occlusion (MCAO) ischemic stroke model for 28 d. Modified neurological severity score (mNSS) and rotarod tests were evaluated at days 1, 4, 7, and 14. Transforming growth factor-beta 1 (TGF-β1), interleukin-1 receptor antagonist (IL-1Ra), and vascular endothelial growth factor (VEGF) were evaluated by enzyme-linked immunosorbent assay (ELISA) at days 4 and 28. Immunohistochemistry expression of aquaporin-4 (AQP4) and neuronal protein marker (NeuN) were performed at days 4 and 28, respectively. Both doses of Neuroncell-EX showed significant lower mNSS scores at days 7 and 14 compared to stroke control. Both Neuroncell-EX groups showed significant longer latency time at day 7, with only 4 × 10⁶ cells/rat group having significant longer time at day 14 than stroke control. At both time points, the 2 × 10⁶ cells/rat group had significantly higher TGF-β1 and IL-1Ra levels, with significantly increased TGF-β1 only observed in 4 × 10⁶ cells/rat group at day 4 compared to stroke control. The VEGF levels were significantly lower at day 4 but then significantly increased at day 28 in both Neuroncell-EX groups than stroke control. AQP4 expression was significantly higher in stroke control compared to healthy control at day 4. Both doses of Neuroncell-EX showed significantly higher NeuN expression compared to stroke control at day 28. There is a weak correlation between TGF-β1 with VEGF and inversely with AQP4. These results suggest that Neuroncell-EX is feasible and effective in promoting functional recovery and neuroprotection in ischemic rats, potentially through immunomodulation, angiogenesis, and neurogenesis mechanisms.

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.

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.

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.

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.

Neurocardiology is an evolving field focusing on the interplay between the nervous system and cardiovascular system that can be used to describe and understand many pathologies. Acute ischemic stroke can be understood through this framework of an interconnected, reciprocal relationship such that ischemic stroke occurs secondary to cardiac pathology (the Heart-Brain axis), and cardiac injury secondary to various neurological disease processes (the Brain-Heart axis). The timely assessment, diagnosis, and subsequent management of cerebrovascular and cardiac diseases is an essential part of bettering patient outcomes and the progression of medicine. Artificial intelligence (AI) and machine learning (ML) are robust areas of research that can aid diagnostic accuracy and clinical decision making to better understand and manage the disease of neurocardiology. In this review, we identify some of the widely utilized and upcoming AI/ML algorithms for some of the most common cardiac sources of stroke, strokes of undetermined etiology, and cardiac disease secondary to stroke. We found numerous highly accurate and efficient AI/ML products that, when integrated, provided improved efficacy for disease prediction, identification, prognosis, and management within the sphere of stroke and neurocardiology. In the focus of cryptogenic strokes, there is promising research elucidating likely underlying cardiac causes and thus, improved treatment options and secondary stroke prevention. While many algorithms still require a larger knowledge base or manual algorithmic training, AI/ML in neurocardiology has the potential to provide more comprehensive healthcare treatment, increase access to equitable healthcare, and improve patient outcomes. Our review shows an evident interest and exciting new frontier for neurocardiology with artificial intelligence and machine learning.

Riboflavin kinase (RFK, also called flavokinase) is a catalytic enzyme that converts riboflavin to its active form in vivo. Dysfunction of the RFK gene has been associated with susceptibility to ischemic stroke. However, the protective role and mechanisms of RFK in ischemic stroke have not been elucidated.

Lentivirus-mediated RFK knock-up (RFK( +)) and knock-down (RFK(-)) were used to investigate the protective effect and mechanism of RFK in the rat middle cerebral artery occlusion (MCAO) model in vivo and in the oxygen and glucose deprivation (OGD) model of neurons in vitro; and the dependence of the protective effect of RFK on flavins was also investigated.

We demonstrated that RFK was an endogenous protein against ischemia brain injury both in vivo and in vitro experiments. RFK inhibited cerebral infarction, cerebral edema and neuronal apoptosis after cerebral ischemia. Its mechanisms include inhibition of the protein expression of Caspase 12 and Caspase 3 induced by cerebral ischemia, and thus inhibiting endoplasmic reticulum stress (ERS) and neuronal apoptosis; the protective effect of RFK depends on the presence of the flavoprotein Ero1; exogenous riboflavin supplementation protected cortical neurons from ischemic injury and prolonged the lifespan in stroke-prone spontaneously hypertensive rats with low RFK gene function, but this protective effect is limited and cannot completely reverse the decreasing trend of neuronal tolerance to ischemic injury caused by RFK gene dysfunction; the protective effect of RFK against ischemic injury is independent of the presence of flavins and their concentrations.

The present study demonstrates that RFK is an important regulatory molecule against ischemia brain injury and its mechanism involves inhibition of ERS. The protective effect of RFK is independent of the presence of flavins and their concentrations. RFK deserves further investigation as a promising target gene for the detection of stroke susceptibility. Flavins may be used as a preventive or adjunctive treatments for ischemic brain injury.

Stroke, as a neurological disorder with a poor overall prognosis, has long plagued the patients. Current stroke therapy lacks effective treatments. Ferroptosis has emerged as a prominent subject of discourse across various maladies in recent years. As an emerging therapeutic target, notwithstanding its initial identification in tumor cells associated with brain diseases, it has lately been recognized as a pivotal factor in the pathological progression of stroke. Acyl-CoA synthetase long-chain family member 4 (ACSL4) is a potential target and biomarker of catalytic unsaturated fatty acids mediating ferroptosis in stroke. Specifically, the upregulation of ACSL4 leads to heightened accumulation of lipid peroxidation products and reactive oxygen species (ROS), thereby exacerbating the progression of ferroptosis in neuronal cells. ACSL4 is present in various tissues and involved in multiple pathways of ferroptosis. At present, the pharmacological mechanisms of targeting ACSL4 to inhibit ferroptosis have been found in many drugs, but the molecular mechanisms of targeting ACSL4 are still in the exploratory stage. This paper introduces the physiopathological mechanism of ACSL4 and the current status of the research involved in ferroptosis crosstalk and epigenetics, and summarizes the application status of ACSL4 in modern pharmacology research, and discusses the potential application value of ACSL4 in the field of stroke.

Over 80% of stroke survivors experience walking dysfunction, impacting quality of life. Rehabilitation is crucial for gait recovery, and accurate assessments facilitate tailored programs. While computerized gait analysis is the gold standard, it is costly and requires specialized training, making observational gait analysis (OGA) more common. However, OGA can also be time-consuming. This study validates the Malta Gait Scale (MGS), a concise, illustrated 7-item observational tool using video recordings for gait measurements. The aim is to provide an effective, time-efficient method for gait evaluations by comparing the MGS with the established Wisconsin Gait Scale (WGS) and Gait Assessment Intervention Tool (GAIT), which have 14 and 31 items, respectively. Forty-nine participants were included in a retrospective study to validate the MGS. We evaluated its reliability using weighted Cohen's kappa (κ) for intrarater and interrater reliability. Concurrent validity was assessed by comparing the MGS with the WGS and GAIT scales using Spearman's rho (ρ). The Wilcoxon test assessed the efficacy of the MGS in detecting rehabilitation-induced changes, differentiating healthy from stroke participants, and evaluating time efficiency. The MGS demonstrated almost perfect agreement, with interrater and intrarater κ values of 0.952 and 0.977, respectively. It showed high positive correlations with the WGS and GAIT, with ρ values of 0.898 and 0.877. MGS required an average administration time of 7 min and 29 s, significantly less than the WGS (27 min and 46 s) and GAIT (50 min and 6 s) (p < 0.001). Following rehabilitation, significant improvements were observed in patients using both the MGS and WGS scales (p = 0.018), and the MGS effectively distinguished between healthy individuals and stroke patients (p < 0.001). The MGS is a valid, reliable, and efficient tool for gait assessment in stroke survivors, supporting smartphone use and facilitating rapid measurements in clinical settings where time is critical.

Neurodegenerative disorders arise when nerve cells in the brain or peripheral nervous system gradually lose functions and eventually die. Although certain therapies may alleviate some of the physical and mental symptoms associated with neurodegenerative disorders, hence slowing their progression, but no sure-shot treatment is currently available. It was shown that the rise in life expectancy and the number of elderly people in the community led to an increasing trend in the incidence and prevalence of neurodegenerative disease. Phytomolecules are demonstrating their effectiveness in combating, regression, and delaying various diseases. Genistein is one of soy isoflavone with antioxidant, anti-inflammatory, and estrogenic effects. Researchers demonstrated that Genistein treatment significantly reduced hyperglycemia, improved cognitive performance by modulating acetylcholinesterase activity and oxidative stress, and alleviated neuroinflammatory conditions in mice. This paper evaluates (in vivo and in vitro) various molecular targets of isoflavones and their ability to effectively counter several neurodegenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases and amyotrophic lateral sclerosis. In this review, we aim to provide an overview of the role that genistein plays in delaying the development of neurodegenerative disorders.

The accumulation of heavy metals in soil and plants poses risks to food safety. Human exposure to heavy metals has been linked to stroke risk, though research on this connection is limited and findings are inconsistent.

We estimated the associations of 7 blood metals [cadmium (Cd), lead (Pb), mercury (Hg), manganese (Mn), copper (Cu), selenium (Se), and zinc (Zn)] with the risk of stroke among 11,803 U.S. adults. Logistic regression account for the intricate sampling design and restricted cubic spline (RCS) was used to explore the associations between single heavy metal and stroke risk. The weighted quantile sum (WQS) and quantile g-computation (qgcomp) were employed to explore the joint effects of seven metals on stroke. Potential confounders were adjusted.

After adjusting for the potential confounders, the logistic regression analysis showed the log-transformed Cd and Zn level was associated with stroke (All p < 0.05). After adjusting for the potential confounders, the logistic regression analysis showed the log-transformed Cd and Zn level was associated with stroke (All p < 0.05). WQS and qgcomp analyses consistently demonstrated a positive correlation between metals-mixed exposure and stroke risk, identifying Cd and Cu as key contributors to the outcomes, while Zn may serve as a protective factor.

These findings indicated that heavy metal exposure is associated with stroke risk, and the protective effect of Zn on stroke risk deserves further research to verify.

Stroke outcomes are typically assessed using objective scales focused on severity and functional ability that may overlook subtle cognitive changes and fail to account for patients' perceptions of recovery and quality of life. This study aimed to compare patient-reported outcomes (PROs) to objective recovery metrics in patients with minor stroke and identify factors associated with perceived recovery and quality of life.

Data from 134 patients with minor stroke were prospectively collected at 1-, 6-, and 12-months post-infarct. Objective assessments measured stroke severity, functional outcomes, activities of daily living, and global cognitive function. PROs included assessments of function, depression, fatigue, symptomatic improvement, and quality of life. Regression models were used to evaluate the relationship between subjective PROs and physician-obtained measures.

Analyses revealed an important role for mental health factors in subjective measures of recovery, though cognitive dysfunction was not significantly associated with either subjective improvement or quality of life despite being commonly endorsed. Depression and fatigue were inversely associated with both satisfaction and quality of life, along with stroke severity and overall functional impairment during both short- and long-term recovery periods. The impact of depression on quality of life increased over time, while stroke severity and functional status were associated with perceived symptomatic improvement at all time points.

For patients with minor stroke, depression is negatively associated with perception of symptomatic recovery and quality of life, particularly at later time points. Addressing post-stroke depression may improve patient-reported outcomes, though further research is needed to determine its impact on broader measures of post-stroke morbidity.