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The pathway of Janus-activated kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) (termed as JAK2/STAT3) plays an active role in stroke-related inflammation induced by ischemic stress. Gastrodin, the primary compound in Gastrodia elata Bl, has been identified for its notable neuroprotective effects and demonstrated to ameliorate cerebral ischemia-reperfusion but its exact mechanisms governing this defense are still unclear. This study aims to investigate whether gastrodin can regulate mitochondrial function via the JAK2/STAT3 pathway to limit cerebral ischemia-reperfusion. In vivo, gastrodin significantly reduced infarct volume, improved neurobiological function, attenuated neuronal apoptosis, oxidative stress, mitochondrial impairment, mtDNA leakage, and inflammatory responses. At the cellular level, gastrodin administration rescued OGD/R-induced cell apoptosis, oxidative stress, and mitochondrial dysfunction. Mechanistically, gastrodin notably suppressed Toll-like receptor 9 (TLR9) expression, important for the recognition of disrupted endogenous DNA to produce inflammatory reactions. Furthermore, gastrodin mitigated inflammation by inhibiting JAK2/STAT3 signaling, influencing inflammatory factors to aggravate inflammation. Notably, the effects of gastrodin were abolished by Coumermycin A1 (C-A1), a JAK2 agonist, validating the role of JAK2/STAT3 signaling. In summary, gastrodin enhances the protective effect against mitochondrial damage in ischemic stroke by inhibiting JAK2/STAT3 signaling. Gastrodin is a possible therapy for cerebral ischemia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study employs machine learning and single-cell transcriptome sequencing (scRNA-seq) analysis to unearth novel biomarkers and delineate the immune characteristics of ischemic stroke (IS), thereby contributing fresh insights into IS treatment strategies.Our research leverages gene expression data sourced from the GEO database. We undertake weighted gene co-expression network analysis (WGCNA) to filter pertinent genes and subsequently employ machine learning algorithms for the identification of feature genes. Concurrently, we rigorously execute quality control measures, dimensionality reduction techniques, and cell annotation on the scRNA-seq data to pinpoint differentially expressed genes (DEGs). The identification of core genes, denoted as Hub genes, among the feature genes and DEGs, is achieved through meticulous overlapping analysis. We illuminate the immune characteristics of these Hub genes using a suite of analytical tools, encompassing CIBERSORT, MCPcounter, and pseudotemporal analysis, all based on immune cell annotations and single-cell transcriptome data.Subsequently, we harness the CMap database to prognosticate potential therapeutic drugs and scrutinize their associations with the identified Hub genes. Our findings unveil robust linkages between three pivotal Hub genes-namely, RNF13, VASP, and CD163-and specific immune cell types such as T cells and neutrophils. These Hub genes predominantly manifest in macrophages and microglial cells within the scRNA-seq immune cell population, exhibiting variances across different stages of cellular differentiation. In conclusion, this study unearths highly pertinent biomarkers for IS diagnosis and elucidates IS-induced immune infiltration characteristics, thus providing a firm foundation for a comprehensive exploration of potential immune mechanisms and the identification of novel therapeutic targets for IS., (© 2024. The Author(s).)

Background: Brain microglia and infiltrating monocyte-derived macrophages are vital in preserving blood vessel integrity after stroke. Understanding mechanisms that induce immune cells to adopt vascular-protective phenotypes may hasten the development of stroke treatments. IL-33 is a potent chemokine released from damaged cells, such as CNS glia after stroke. The activation of IL-33/ST2 signaling has been shown to promote neuronal viability and white matter integrity after ischemic stroke. The impact of IL-33/ST2 on blood-brain barrier (BBB) integrity, however, remains unknown. The current study fills this gap and reveals a critical role of IL-33/ST2 signaling in macrophage-mediated BBB protection after stroke., Methods: Transient middle cerebral artery occlusion (tMCAO) was performed to induce ischemic stroke in wildtype (WT) versus ST2 knockout (KO) male mice. IL-33 was applied intranasally to tMCAO mice with or without dietary PLX5622 to deplete microglia/macrophages. ST2 KO versus WT bone marrow or macrophage cell transplantations were used to test the involvement of ST2 + macrophages in BBB integrity. Macrophages were cocultured in transwells with brain endothelial cells (ECs) after oxygen-glucose deprivation (OGD) to test potential direct effects of IL33-treated macrophages on the BBB in vitro., Results: The ST2 receptor was expressed in brain ECs, microglia, and infiltrating macrophages. Global KO of ST2 led to more IgG extravasation and loss of ZO-1 in cerebral microvessels 3 days post-tMCAO. Intranasal IL-33 administration reduced BBB leakage and infarct severity in microglia/macrophage competent mice, but not in microglia/macrophage depleted mice. Worse BBB injury was observed after tMCAO in chimeric WT mice reconstituted with ST2 KO bone marrow, and in WT mice whose monocytes were replaced by ST2 KO monocytes. Macrophages treated with IL-33 reduced in vitro barrier leakage and maintained tight junction integrity after OGD. In contrast, IL-33 exerted minimal direct effects on the endothelial barrier in the absence of macrophages. IL-33-treated macrophages demonstrated transcriptional upregulation of an array of protective factors, suggesting a shift towards favorable phenotypes., Conclusion: Our results demonstrate that early-stage IL-33/ST2 signaling in infiltrating macrophages reduces the extent of acute BBB disruption after stroke. Intranasal IL-33 administration may represent a new strategy to reduce BBB leakage and infarct severity., (© 2024. The Author(s).)

Background: Antiphospholipid antibodies (aPLs) have been reported to be involved in platelet-mediated thrombosis and inflammation, but the impact on the prognosis of ischemic stroke remains unclear. We aimed to examine whether the association between baseline platelet count (PLT) and long-term clinical outcomes within 2 years after ischemic stroke onset is modulated by aPLs., Methods and Results: A total of 2938 patients with ischemic stroke were included in this prospective cohort study. Cox proportional hazards regression models were used to assess the association between the baseline PLT stratified by aPLs status and 2-year clinical outcomes after stroke onset, and an interaction effect between PLT and aPLs on clinical outcomes was tested by likelihood ratio test. There was a significant interaction effect of aPLs and PLT on recurrent stroke ( P interaction =0.002) and cardiovascular events ( P interaction =0.001) within 2 years after stroke onset. After multivariate adjustment, high PLT was associated with increased risks of recurrent stroke (hazard ratio [HR], 2.78 [95% CI, 1.03-7.45]; P trend =0.039) and cardiovascular events (HR, 2.58 [95% CI, 1.12-5.90]; P trend =0.024) when 2 extreme tertiles were compared among patients with aPL positive, but not among those with aPL negative., Conclusions: The aPLs had a modifying effect on the association between PLT and clinical outcomes within 2 years after ischemic stroke onset. Increased PLT was associated with recurrent stroke and cardiovascular events after ischemic stroke onset among patients with aPL positive, but not in those with aPL negative.

Background: We aimed to investigate the relationship between systemic immune-inflammation index (SII) and short-term mortality in acute ischemic stroke (AIS) with internal carotid artery (ICA) severe stenosis and stroke associated pneumonia (SAP) patients., Methods: Information on general demographic, laboratory data, CT angiography, magnetic resonance angiography, or digital subtraction angiography were obtained. The predictive power was evaluated by assessing the area under the receiver operating characteristic (ROC) curve. The logistic regression was performed to assess the association of SII and short-term mortality in severe stenosis ICA-AIS and SAP patients., Result: Among 342 patients with severe stenosis ICA-AIS and SAP, death occurred in 66 patients during 120 days follow-up. Multivariate regression analyses indicated that increased SII predicts higher mortality in 120 days follow-up, and the risk of short-term mortality in SII > 666.31 × 10 9 /L group is increased 4.671-fold. Patients with SII > 666.31 × 10 9 /L had higher proportion of male, hypertension, smoking, higher admission NIHSS score, higher systolic blood pressure, and higher proportion of 120 days mortality. Higher SII predicted a worse 120 days mortality was worked out by Kaplan-Meier methods., Conclusion: An elevated SII was remarkably associated with 120 days mortality in severe stenosis ICA-AIS and SAP patients., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Background: Antiphospholipid antibodies (aPL), including lupus anticoagulant, antibodies against β 2 glycoprotein I (anti-β2GPI), and anticardiolipin (aCL) antibodies are associated with ischemic stroke (IS). Their prevalence and clinical relevance in atrial fibrillation (AF) remain unclear., Objectives: To assess whether aPL are associated with increased risk of IS in AF patients despite anticoagulation., Methods: We conducted a post hoc analysis of aPL using blood samples from 243 consecutive AF patients enrolled in a cohort study. Markers of a prothrombotic state, including endogenous thrombin potential, fibrin clot permeability, and lysis time, were measured at baseline. During a median follow-up of 52 months, IS/transient ischemic attack and major bleeding were recorded., Results: We observed aPL at a moderate or high titer in 51 (21%) patients, including 17 (7%) with anti-β2GPI, 19 (7.8%) with aCL antibodies, and 37 (15.2%) with lupus anticoagulant. aPL-positive patients were more likely to have prior stroke (P = .01) and be active smokers (P = .03), along with increased endogenous thrombin potential (P = .02), without any changes in fibrin clot properties. Anti-β2GPI (hazard ratio, 4.38; 95% CI, 1.58-12.19) and aCL (hazard ratio, 4.70; 95% CI, 1.80-12.30) at a moderate or high titer were associated with IS during follow-up (n = 20; 1.9% per year). There were 23 major bleedings (2.1% per year) and 20 deaths (1.9% per year), which were not associated with aPLs., Conclusion: Our study showed a relatively high prevalence of aPL positivity in AF patients, which was linked to an increased risk of IS/transient ischemic attack. This suggests that screening for aPL might help optimize anticoagulant therapy in such patients., Competing Interests: Declaration of competing interests All authors have no competing interests to disclose., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Background: Ischemic stroke is one of the leading causes of chronic disability worldwide, and stroke-induced heart damage can lead to death. According to research, patients with a variety of brain disease have good clinical results after vagus nerve stimulation (VNS). After ischemic stroke, mast cells (MCs) degranulate and release a large number of mediators, which may cause systemic inflammation. Chymase secreted by MCs can increase the levels of pathological angiotensin II (AngⅡ), which plays a crucial role in the deterioration of heart disease. Our goal was to develop a minimally invasive, targeted, and convenient VNS approach to assess the impact of VNS and to clarify the relationship between VNS and MCs in the prognosis of patients with myocardial atrophy after acute ischemic stroke., Methods: In this study, we verified the role of VNS in the treatment of myocardial atrophy after stroke and its molecular mechanism using a rat model of middle cerebral artery occlusion (MCAO/r). Behavioral studies were assessed using neurobehavioral deficit scores. Enzyme-linked immunosorbent assays, immunofluorescence staining, Western blotting and qRT-PCR were used to analyze the expression levels of myocardial atrophy, MC and inflammatory markers in rat hearts., Results: VNS improved myocardial atrophy in MCAO/r rats, inhibited MC activation, reduced the expression of chymase and AngⅡ, and inhibited the expression of proinflammatory factors. The chymase activator C48/80 reversed these effects of VNS. Chymase activation inhibited the effect of VNS on myocardial atrophy in MCAO/r rats, increased AngⅡ expression and aggravated inflammation and autophagy. The myocardial atrophy of MCAO/r rats was improved after chymase inhibition, and AngⅡ expression, inflammation and autophagy were reduced. Our results suggest that VNS may reduce the expression of chymase and AngⅡ by inhibiting MC activation, thereby improving myocardial atrophy and reducing inflammation and autophagy in MCAO/r rats. Inhibition of MC activation may be an effective strategy for treating myocardial atrophy after stroke., Conclusions: VNS inhibits MC activation and reduces the expression of chymase and AngII, thereby alleviating myocardial atrophy, inflammation and autophagy after stroke., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Ischemic stroke (IS) is a critical medical condition that results in significant neurological deficits and tissue damage, affecting millions worldwide. Currently, there is a significant lack of reliable tools for assessing and predicting IS outcomes. The inflammatory response following IS may exacerbate tissue injury or provide neuroprotection. This review sought to summarize current knowledge on the IL-1 family's involvement in IS, which includes pro-inflammatory molecules, such as IL-1α, IL-1β, IL-18, and IL-36, as well as anti-inflammatory molecules, like IL-1Ra, IL-33, IL-36A, IL-37, and IL-38. The balance between these opposing inflammatory processes may serve as a biomarker for determining patient outcomes and recovery paths. Treatments targeting these cytokines or their receptors show promise, but more comprehensive research is essential to clarify their precise roles in IS development and progression.

Background: Ischaemic stroke is a leading cause of death and severe disability worldwide. Given the importance of protein synthesis in the inflammatory response and neuronal repair and regeneration after stroke, and that proteins are acquired by ribosomal translation of mRNA, it has been theorised that ribosome biogenesis may have an impact on promoting and facilitating recovery after stroke. However, the relationship between stroke and ribosome biogenesis has not been investigated., Methods: In the present study, a ribosome biogenesis gene signature (RSG) was developed using Cox and least absolute shrinkage and selection operator (LASSO) analysis. We classified ischaemic stroke patients into high-risk and low-risk groups using the obtained relevant genes, and further elucidated the immune infiltration of the disease using ssGSEA, which clarified the close relationship between ischaemic stroke and immune subgroups. The concentration of related proteins in the serum of stroke patients was determined by ELISA, and the patients were divided into groups to evaluate the effect of the ribosome biogenesis gene on patients. Through bioinformatics analysis, we identified potential IS-RSGs and explored future therapeutic targets, thereby facilitating the development of more effective therapeutic strategies and novel drugs against potential therapeutic targets in ischaemic stroke., Results: We obtained a set of 12 ribosome biogenesis-related genes (EXOSC5, MRPS11, MRPS7, RNASEL, RPF1, RPS28, C1QBP, GAR1, GRWD1, PELP1, UTP, ERI3), which play a key role in assessing the prognostic risk of ischaemic stroke. Importantly, risk grouping using ribosome biogenesis-related genes was also closely associated with important signaling pathways in stroke. ELISA detected the expression of C1QBP, RPS28 and RNASEL proteins in stroke patients, and the proportion of neutrophils was significantly increased in the high-risk group., Conclusions: The present study demonstrates the involvement of ribosomal biogenesis genes in the pathogenesis of ischaemic stroke, providing novel insights into the underlying pathogenic mechanisms and potential therapeutic strategies for ischaemic stroke., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Zhang, Liao, He and Chen.)

Objective: Stroke is a chronic health problem that affects all areas of life. The presence of thyroid autoantibodies can augment the severity of stroke. The aim of this work is to investigate whether there is a relationship between the site of stroke involvement and the anti-thyroid peroxidase antibody (anti-TPO) or not. This is the first study in the English-language literature., Methods: A total of 39 patients with a diagnosis of acute ischemic stroke were included, and the cases under 18 years of age with an infection and the ones with autoimmune diseases other than Hashimoto's thyroiditis were excluded from the study design. The patients' age, gender, smoking status, comorbid conditions, and stroke localization in brain imaging were recorded. The region involving the anterior circulation area originating from the internal carotid artery was evaluated as anterior, and the region possessing the vertebrobasilar circulation area from the vertebral arteries was considered posterior involvement. Thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), C-reactive protein (CRP), sedimentation, and anti-TPO were retrospectively analyzed., Results: As a consequence, gender distribution, smoking, comorbid conditions, TSH, T3, T4, triglyceride, HDL, LDL, CRP, and sedimentation did not differ significantly, while the age of the posterior-located stroke was lower than that of the cases with the anterior. The anti-TPO value was significantly lower in posterior-located strokes than in the anterior system., Conclusion: In summary, the anti-TPO value was recognized as higher in the anterior stroke localization. Thyroiditis and accompanying anti-TPO autoantibody positivity are conditions that should not be ignored by thyroidologists and thyroid-health providers.

Background : A number of acute ischemic stroke (AIS) cases may be misdiagnosed as transient ischemic attack (TIA), due to no infarct on initial computed tomography scan and/or mild deficits upon presentation. Several studies have found that the neutrophil-lymphocyte ratio (NLR) is an accurate differential diagnostic biomarker for AIS versus TIA; however, no study has evaluated the use of the NLR in differentiating CT negative AIS from TIA. Furthermore, the systemic immune-inflammation index (SII) is a relatively novel immune biomarker that has been shown to be positively correlated with AIS severity, poor functional outcomes and mortality. The purpose of this study is to determine if NLR or SII can be used as a diagnostic biomarker for the differential diagnosis of mild AIS with a negative CT upon admission and TIA. Methods : We performed a retrospective medical record review of patients diagnosed with either AIS or TIA. We collected peripheral white blood cell counts within 24 h of symptom onset and calculated the NLR and SII. Logistic regression was utilized to determine if NLR or SII are significant predictors of CT negative mild AIS. Results: CT negative mild AIS patients were 2 times as likely to have an NLR ≥ 2.71 compared to TIA patients, and CT negative mild AIS patients were 2.1 times as likely to have an SII ≥ 595 compared to TIA patients. Conclusion : NLR and SII are easily obtained biomarkers that can be used in early clinical decision making in cases of mild AIS with negative CT scan upon admission.

Background: Immunity play a pivotal role in the risk of ischemic stroke, and studies have also shown a relationship between ischemic stroke and autoimmune diseases. In light of this we conducted a prospective cohort study to elucidate the impact of antiphospholipid antibodies (aPLs), antinuclear antibodies (ANA), and anti-extractable nuclear antigen autoantibodies (anti-ENA) on the prognosis of ischemic stroke., Methods: 245 stroke patients were recruited in this single-center study and followed up with for 3 years. Autoantibodies, including aPLs (ACA, anti-β2GPI, LA), ANA and anti-ENA were evaluated in recurrent ischemic stroke (RIS) and nonrecurrent ischemic stroke (nonRIS). Stroke severity was judged using the National Institutes of Health Stroke Scale (NIHSS). For preventive treatment, 42 IS patients with positive aPLs + ANA/anti-ENA were randomized 1:1 into a hydroxychloroquine (HCQ) treatment group and a control group, and the prognoses were compared., Results: The positive rate of ACA IgG (p = 0.018), anti-β2GPI IgG (p = 0.047), LA (p = 0.023), and aPLs + ANA/anti-ENA (p = 0.000) were significantly higher in patients with RIS compared to patients with nonRIS, and aPLs + ANA/anti-ENA (HR2.31, 95 % CI1.02-5.25, p = 0.046) and hypertension (HR2.50, 95 % CI1.17-5.35, p = 0.018) were the independent risk factors of recurrence. There were differences in NIHSS at month 36 between those positive and negative for aPLs + ANA/anti-ENA (p = 0.001, Eta 2 = 0.052), anti-ENA (p = 0.016, Eta 2 = 0.030), ANA (p = 0.035, Eta 2 = 0.022), and LA (p = 0.016, Eta 2 = 0.028). Furthermore, the recurrence rate of the HCQ treatment group was lower than that of the control group (p = 0.024)., Conclusions: Co-positivity of aPLs and ANA/anti-ENA is an independent risk factor for RIS. However, HCQ therapy may reduce the recurrence rate of IS for these patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Leukocyte immunoglobulin-like receptor B4 (LILRB4) plays a significant role in regulating immune responses. LILRB4 in microglia might influence the infiltration of peripheral T cells. However, whether and how LILRB4 expression aggravates brain damage after acute ischemic stroke remains unclear. This study investigates the role of LILRB4 in modulating the immune response and its potential protective effects against ischemic brain injury in mice., Methods and Results: Microglia-specific LILRB4 conditional knockout (LILRB4-KO) and overexpression transgenic (LILRB4-TG) mice were constructed by a Cre-loxP system. Then, they were used to investigate the role of LILRB4 after ischemic stroke using a transient middle cerebral artery occlusion (tMCAO) mouse model. Spatial transcriptomics analysis revealed increased LILRB4 expression in the ischemic hemisphere. Single-cell RNA sequencing (scRNA-seq) identified microglia-cluster3, an ischemia-associated microglia subcluster with elevated LILRB4 expression in the ischemic brain. Flow cytometry and immunofluorescence staining showed increased CD8 + T cell infiltration into the brain in LILRB4-KO-tMCAO mice. Behavioral tests, cortical perfusion maps, and infarct size measurements indicated that LILRB4-KO-tMCAO mice had more severe functional deficits and larger infarct sizes compared to Control-tMCAO and LILRB4-TG-tMCAO mice. T cell migration assays demonstrated that LILRB4-KD microglia promoted CD8 + T cell recruitment and activation in vitro, which was mitigated by CCL2 inhibition and recombinant arginase-1 addition. The scRNA-seq and spatial transcriptomics identified CCL2 was predominantly secreted from activated microglia/macrophage and increased CCL2 expression in LILRB4-KD microglia, suggesting a chemokine-mediated mechanism of LILRB4., Conclusion: LILRB4 in microglia plays a crucial role in modulating the post-stroke immune response by regulating CD8 + T cell infiltration and activation. Knockout of LILRB4 exacerbates ischemic brain injury by promoting CD8 + T cell recruitment. Overexpression of LILRB4, conversely, offers neuroprotection. These findings highlight the therapeutic potential of targeting LILRB4 and its downstream pathways to mitigate immune-mediated damage in ischemic stroke., (© 2024. The Author(s).)

The adaptive response occurs only after 7-10 days of antigen presentation. Nevertheless, the autoreactive T cells infiltrate the stroke lesion within the first 48 h. Thus, we hypothesized that the unconventional lymphocytes as invariant natural killer T cells (iNKT) and γδT cells that share immediate innate and delayed adaptive response features are involved in acute stroke pathophysiology. We assessed prospectively the quantity of circulating iNKT cells, γδT cells, and NK cells with flow cytometry in 52 subjects within three months after stroke, and we compared the results with those obtained in age-, sex-, and vascular risk factor-matched controls. We studied lymphocyte parameters regarding clinical outcomes, infarct volume, stroke-associated infection (SAI), and burden risk factors. The reduced number of circulating γδT cells and decreased percentage of the Vδ2 subset in the acute phase of stroke correlated with worse neurological status in the recovery phase. In subjects treated with thrombolysis and those who developed SAI, a lower percentage of γδT cells in the 90-day follow-up was observed. An increased percentage of iNKT cells in the acute and subacute phases of stroke was observed, and it was related to the worse clinical status. The circulating NK cells do not change temporarily or affect the outcomes after stroke. It seems that γδT cells play a long-lasting role in ischemic stroke, mainly related to the Vδ2 subset. The role of iNKT cells appears to be detrimental, especially in the acute and subacute phases of stroke. The effect of circulating NK cells on the outcome after stroke seems negligible.

Background: Understanding the association of peripheral inflammation and post-stroke depressive symptomology (PSDS) might provide further insights into the complex etiological mechanism of organic depression. However, studies focusing on the longitudinal patterns of PSDS were limited and it remained unclear whether peripheral inflammation influences the occurrence and development of PSDS., Methods: A total of 427 prospectively enrolled and followed ischemic stroke patients were included in the analytical sample. Depressive symptomology was assessed on four occasions during 1 year after ischemic stroke. Peripheral inflammatory proteins on admission and repeated measures of peripheral immune markers in three stages were collected. Latent class growth analysis (LCGA) was employed to delineate group-based trajectories of peripheral immune markers and PSDS. Multinomial regression was performed to investigate the association of peripheral inflammation with PSDS trajectories., Results: Four distinct trajectories of PSDS were identified: stable-low (n = 237, 55.5 %), high-remitting (n = 120, 28.1 %), late-onset (n = 44, 10.3 %), and high-persistent (n = 26, 6.1 %) PSDS trajectories. The elevation of peripheral fibrinogen on admission increased the risk of high-persistent PSDS in patients with early high PSDS. Additionally, chronic elevation of innate immune levels might not only increase the risk of high-persistent PSDS in patients with early high PSDS but also increase the risk of late-onset PSDS in patients without early high PSDS. The elevation of adaptive immune levels in the convalescence of ischemic stroke may contribute to the remission of early high PSDS., Conclusions: Peripheral immunity could influence the development of PSDS, and this influence might have temporal heterogeneity. These results might provide vital clues for the inflammation hypothesis of PSD., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In 2024, over 775 million cases of COVID-19 were recorded, including approximately 7 million deaths, indicating its widespread and dangerous nature. The disease is caused by the SARS-CoV-2 virus, which can manifest a wide spectrum of symptoms, from mild infection to respiratory failure and even death. Neurological symptoms, such as headaches, confusion, and impaired consciousness, have also been reported in some COVID-19 patients. These observations suggest the potential of SARS-CoV-2 to invade the central nervous system and induce neuroinflammation during infection. This review specifically explores the relationship between SARS-CoV-2 infection and selected neurological diseases such as multiple sclerosis (MS), ischemic stroke (IS), and Alzheimer's disease (AD). It has been observed that the SARS-CoV-2 virus increases the production of cytokines whose action can cause the destruction of the myelin sheaths of nerve cells. Subsequently, the body may synthesize autoantibodies that attack nerve cells, resulting in damage to the brain's anatomical elements, potentially contributing to the onset of multiple sclerosis. Additionally, SARS-CoV-2 exacerbates inflammation, worsening the clinical condition in individuals already suffering from MS. Moreover, the secretion of pro-inflammatory cytokines may lead to an escalation in blood clot formation, which can result in thrombosis, obstructing blood flow to the brain and precipitating an ischemic stroke. AD is characterized by intense inflammation and heightened oxidative stress, both of which are exacerbated during SARS-CoV-2 infection. It has been observed that the SARS-CoV-2 demonstrates enhanced cell entry in the presence of both the ACE2 receptor, which is already elevated in AD and the ApoE ε4 allele. Consequently, the condition worsens and progresses more rapidly, increasing the mortality rate among AD patients. The above information underscores the numerous connections between SARS-CoV-2 infection and neurological diseases.

Stroke is a leading cause of permanent disability worldwide. Despite intensive research over the last decades, key anti-inflammatory strategies that have proven beneficial in pre-clinical animal models have often failed in translation. The importance of neutrophils as pro- and anti-inflammatory peripheral immune cells has often been overlooked in ischemic stroke. However, neutrophils rapidly infiltrate into the brain parenchyma after stroke and secrete an array of pro-inflammatory factors including reactive oxygen species, proteases, cytokines, and chemokines exacerbating damage. In this study, we demonstrate the neuroprotective and anti-inflammatory effect of benserazide, a clinically used DOPA decarboxylase inhibitor, using both in vitro models of inflammation and in vivo mouse models of focal cerebral ischemia. Benserazide significantly attenuated PMA-induced NETosis in isolated human neutrophils. Furthermore, benserazide was able to protect both SH-SY5Y and iPSC-derived human cortical neurons when challenged with activated neutrophils demonstrating the clinical relevance of this study. Additional in vitro data suggest the ability of benserazide to polarize macrophages towards M2-phenotypes following LPS stimulation. Neuroprotective effects of benserazide are further demonstrated by in vivo studies where peripheral administration of benserazide significantly attenuated neutrophil infiltration into the brain, altered microglia/macrophage phenotypes, and improved the behavioral outcome post-stroke. Overall, our data suggest that benserazide could serve as a drug candidate for the treatment of ischemic stroke. The importance of our results for future clinical trials is further underlined as benserazide has been approved by the European Medicines Agency as a safe and effective treatment in Parkinson's disease when combined with levodopa., (© 2024. The Author(s).)

Aims: To investigate the relationship between peripheral blood lymphocyte subsets and prognosis in patients with acute ischemic stroke (AIS)., Methods: We enrolled 294 patients with AIS and collected peripheral blood samples for analysis of lymphocyte subsets. Prognosis was assessed at 3 months using the modified Rankin Scale (mRS). Association between lymphocyte count and poor outcomes (mRS score >2) was assessed using logistic regression. Individualized prediction models were developed to predict poor outcomes., Results: Patients in the mRS score ≤2 group had higher T-cell percentage (odds ratio [OR] = 0.947; 95% confidence interval [CI]: 0.899-0.998; p = 0.040), CD3 + T-cell count (OR = 0.999; 95% CI: 0.998-1.000; p = 0.018), and CD4 + T-cell count (OR = 0.998; 95% CI: 0.997-1.000; p = 0.030) than those in the mRS score >2 group 1-3 days after stroke. The prediction model for poor prognosis based on the CD4 + T-cell count showed good discrimination (area under the curve of 0.844), calibration (p > 0.05), and clinical utility., Conclusion: Lower T cell percentage, CD3 + , and CD4 + T-cell counts 1-3 days after stroke were independently associated with increased risk of poor prognosis. Individualized predictive model of poor prognosis based on CD4 + T-cell count have good accuracy and may predict disease prognosis., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Frequent incidence of futile recanalization decreases the benefit of endovascular treatment (EVT) in acute ischemic stroke. We hypothesized that the inflammation and immune response after ischemic are associated with futile recanalization. We aimed to investigate the correlation of admission systemic immune-inflammation index (SII) with futile recanalization post EVT., Methods: Patients with successful recanalization (modified Thrombolysis in Cerebral Ischemia angiographic score 2b-3) and maintained artery recanalized after 24 h of EVT were chosen from a prospective nationwide registry study. Futile recanalization was defined as a poor functional outcome (modified Rankin Scale score 3-6) at 90 days, irrespective of a successful recanalization. At admission, SII was calculated as (platelet count × neutrophil count)/lymphocyte count/100. Logistic regression analysis helped to test the relationship of SII with futile recanalization., Results: Among the 1,002 patients included, futile recanalization occurred in 508 (50.70%). No matter whether tested as quartiles or continuous variables, SII was significantly associated with futile recanalization (P < 0.05), and for every one standard deviation increase of SII, the risk of futile recanalization elevated by 22.3% (odds ratio 1.223, 95% confidence interval 1.053-1.444, P = 0.0093). Moreover, no significant interactions could be observed between SII or SII quartiles and age, baseline National Institutes of Health Stroke Scale scores, onset-to-recanalization time, and modified Thrombolysis in Cerebral Ischemia angiographic scores (all P for interaction > 0.05)., Conclusions: Early SII elevation was associated with an increased risk of futile recanalization among patients with EVT. Our results indicated that therapeutic drug targeting hyperreactive immune-inflammation response might be helpful for reducing the incidence of futile recanalization., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: The brain border compartments harbor a diverse population of immune cells and serve as invasion sites for leukocyte influx into the brain following CNS injury. However, how brain-border myeloid cells affect stroke pathology remains poorly characterized., Methods and Results: Here, we showed that ischemic stroke-induced expansion of CXCL2 + neutrophils, which exhibit highly proinflammatory features. We tracked CXCL2 + neutrophils in vivo by utilizing a photoconvertible Kik-GR mouse (fluorescent proteins Kikume Green Red, Kik-GR) and found that brain-infiltrating CXCL2 + neutrophils following ischemic stroke were mainly derived from the brain border rather than the periphery. We demonstrated that CXCL2 neutralization inhibited the formation and releasing of neutrophil extracellular traps (NETs) from in vitro cultured primary neutrophils. Furthermore, CXCL2-neutralizing antibody treatment reduced brain infarcts and improved vascular reperfusion at day 3 postischemic stroke., Conclusions: Collectively, brain border-derived CXCL2 + neutrophil expansion may impair vascular reperfusion by releasing NETs following ischemic stroke., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Immunoinflammation is associated with the development of post-stroke cognitive impairment (PSCI), however, peripheral immunity has not been fully explored. We aimed to investigate the association between PSCI and peripheral immune indicators, including neutrophil, lymphocyte, and mononuclear percentages and counts; the systemic immune inflammation index; platelet-to-lymphocyte ratio; neutrophil-to-lymphocyte ratio (NLR); and lymphocyte-to-monocyte ratio. A total of 224 patients with acute minor ischemic stroke or transient ischemic attack with 6-12 months of follow-up were included. PSCI was defined as a Montreal Cognitive Assessment score < 22 during the follow-up period. We performed logistic regression, subgroup analyses based on age and sex, and further established predictive models. We found that increased innate immunity indicators (neutrophils, neutrophil percentage) increased the risk of PSCI, whereas increased adaptive immunity indicator (lymphocytes) were protective against PSCI, especially in patients aged 50-65 years. Neutrophil percentage and NLR improved the predictive efficacy of the models that included demographic, clinical, and imaging information, with the area under the curve increased from 0.765 to 0.804 and 0.803 (P = 0.042 and 0.049, respectively). We conducted a comprehensive analysis of peripheral immunity in PSCI, providing a novel perspective on the early detection, etiology, and treatment of PSCI., (© 2024. The Author(s).)

Background: Angong Niuhuang Wan (AGNHW, ), is a classical medicinal formula in Traditional Chinese Medicine (TCM) that has been appreciated for its neuroprotective properties in ischemic cerebral injuries, yet its intricate mechanisms remain only partially elucidated., Aims: This study leverages advanced Mass cytometry (CyTOF) to analyze AGNHW's multifaceted immunomodulation effects in-depth, emphasizing previously underexplored areas., Results: AGNHW mitigated monocyte-derived macrophages (MoDM) infiltration in the brain, distinguishing its effects on those from microglia. While the vehicle group exhibited elevated inflammatory markers like CD4, CD8a, and CD44 in ischemic brains, the AGNHW-treated group attenuated their expressions, indicating AGNHW's potential to temper the post-ischemic inflammatory response. Systemically, AGNHW modulated fundamental immune cell dynamics, notably augmenting CD8 + T cells, B cells, monocytes, and neutrophil counts in the peripheral blood under post-stroke conditions. Intracellularly, AGNHW exhibited its targeted modulation of the signaling pathways, revealing a remarked inhibition of key markers like IκBα, indicating potential suppression of inflammatory responses in ischemic brain injuries., Conclusion: This study offers a comprehensive portrait of AGNHW's immunomodulation effects on ischemic stroke, illuminating its dual sites of action-both cerebral and systemic-and its nuanced modulation of cellular and molecular dynamics., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Ischemic stroke (IS) is of increasing concern given the aging population and prevalence of unhealthy lifestyles, with older females exhibiting higher susceptibility. This study aimed to identify practical diagnostic markers, develop a diagnostic model for immunogenic cell death (ICD)-associated IS, and investigate alterations in the immune environment caused by hub genes. Differentially expressed genes associated with ICD in IS were identified based on weighted gene co-expression network analysis and the identification of significant modules. Subsequently, machine learning algorithms were employed to screened hub genes, which were further assessed using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis. A nomogram mode lwas then constructed for IS diagnosis, and its diagnostic value was assessed using a receiver operating characteristic curve. Finally, alterations in immune cell infiltration were assessed within patients with IS, and the pan-cancer expression patterns of hub genes were evaluated. Three hub genes associated with ICD (PDK4, CCL20, and FBL) were identified. The corresponding nomogram model for IS diagnosis could effectively identify older female patients with IS (area under the curve (AUC) = 0.9555). Overall, the three hub genes exhibit good diagnostic value (AUC > 0.8). CCL20 and FBL are significantly associated with the extent of immune cells infiltration. Moreover, a strong link exists between hub gene expression and pan-cancer prognosis. Cumulatively, these results indicate that ICD-related hub genes critically influence IS progression in older females, presenting novel diagnostic and therapeutic targets for personalized treatment., (© 2024. The Author(s).)

Seipin plays a crucial role in lipid metabolism and is involved in neurological disorders. However, the function and mechanism of action of seipin in acute ischemic stroke have not yet been elucidated. Here, we aimed to investigate the effect of seipin on neuroinflammation induced by oxygen-glucose deprivation/reoxygenation (OGD/R) and further explore the molecular mechanism by functional experiments. Our results revealed a significant decrease in seipin mRNA levels, accompanied by enhanced expression of TNF-α in patients with AIS, and a significant negative correlation between seipin and TNF-α was observed. Additionally, there was a negative correlation between seipin levels and the National Institutes of Health Stroke Scale (NIHSS) score. Furthermore, seipin levels were also decreased in middle cerebral artery occlusion/reperfusion (MCAO/R) mice and OGD/R-treated BV2 cells. RNA sequencing analysis showed that seipin knockdown altered the Toll-like receptor 3 (TLR3) signaling pathway. It was further confirmed in vitro that seipin knockdown caused significantly increased secretion of inflammatory factors including TNF-α, interleukin (IL)-1β, and interferon (IFN)-β. Meanwhile, seipin knockdown activated the Tlr3 signal pathway while this effect could be reversed by Tlr3 inhibitor in OGD/R treated BV2 cells. Furthermore, neuroinflammation induced by OGD/R was significantly reduced by seipin overexpression. Overall, our study demonstrate that seipin deficiency aggravates neuroinflammation by activating the TLR3/TRAF3/NF-κB signaling pathway after OGD/R stimuli, and suggest that seipin may be a potential therapeutic target for AIS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Ischemic stroke is the major contributor to morbidity and mortality in people with diabetes mellitus. In ischemic stroke patients, neuroinflammation is now understood to be one of the main underlying mechanisms for cerebral damage and recovery delay. It has been well-established that toll-like receptor 4 (TLR4) signaling pathway plays a key role in neuroinflammation. Emerging research over the last decade has revealed that, compared to ischemic stroke without diabetes mellitus, ischemic stroke with diabetes mellitus significantly upregulates TLR4-mediated neuroinflammation, increasing the risk of cerebral and neuronal damage as well as neurofunctional recovery delay. This review aims to discuss how ischemic stroke with diabetes mellitus amplifies TLR4-mediated neuroinflammation and its consequences. Additionally covered in this review is the potential application of TLR4 antagonists in the management of diabetic ischemic stroke., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ischemic stroke, a disease with high mortality and disability rate worldwide, currently has no effective treatment. The systemic inflammation response to the ischemic stroke, followed by immunosuppression in focal neurologic deficits and other inflammatory damage, reduces the circulating immune cell counts and multiorgan infectious complications such as intestinal and gut dysfunction dysbiosis. Evidence showed that microbiota dysbiosis plays a role in neuroinflammation and peripheral immune response after stroke, changing the lymphocyte populations. Multiple immune cells, including lymphocytes, engage in complex and dynamic immune responses in all stages of stroke and may be a pivotal moderator in the bidirectional immunomodulation between ischemic stroke and gut microbiota. This review discusses the role of lymphocytes and other immune cells, the immunological processes in the bidirectional immunomodulation between gut microbiota and ischemic stroke, and its potential as a therapeutic strategy for ischemic stroke., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Stroke-induced heart syndrome is a feared complication of ischemic stroke, that is commonly encountered and has a strong association with unfavorable prognosis. More research is needed to explore underlying mechanisms and inform clinical decision making. This study aims to explore the relationship between the early systemic immune-inflammation (SII) index and the cardiac complications after acute ischemic stroke., Methods: Consecutive patients with acute ischemic stroke were prospectively collected from January 2020 to August 2022 and retrospectively analyzed. We included subjects who presented within 24 hours after symptom onset and were free of detectable infections or cancer on admission. SII index [(neutrophils × platelets/ lymphocytes)/1000] was calculated from laboratory data at admission., Results: A total of 121 patients were included in our study, of which 24 (19.8 %) developed cardiac complications within 14 days following acute ischemic stroke. The SII level was found higher in patients with stroke-heart syndrome (p<.001), which was an independent predictor of stroke-heart syndrome (adjusted odds ratio 5.089, p=.002)., Conclusion: New-onset cardiovascular complications diagnosed following a stroke are very common and are associated with early SII index., Competing Interests: Competing interests None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Ischemic stroke is the primary reason for human disability and death, but the available treatment options are limited. Hence, it is imperative to explore novel and efficient therapies. In recent years, pyroptosis (a pro-inflammatory cell death characterized by inflammation) has emerged as an important pathological mechanism in ischemic stroke that can cause cell death through plasma membrane rupture and release of inflammatory cytokines. Pyroptosis is closely associated with inflammation, which exacerbates the inflammatory response in ischemic stroke. The level of inflammasomes, GSDMD, Caspases, and inflammatory factors is increased after ischemic stroke, exacerbating brain injury by mediating pyroptosis. Hence, inhibition of pyroptosis can be a therapeutic strategy for ischemic stroke. In this review, we have summarized the relationship between pyroptosis and ischemic stroke, as well as a series of treatments to attenuate pyroptosis, intending to provide insights for new therapeutic targets on ischemic stroke., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Ischemic stroke (IS) is a cerebrovascular disease caused by various factors, and its etiology remains inadequately understood. The role of immune system dysfunction in IS has been increasingly recognized. Our objective was to evaluate whether circulating immune cells causally impact IS risk., Methods: We conducted two-sample Mendelian randomization analyses to evaluate the causal effects of 731 immune cell traits on IS, utilizing publicly available genome-wide association studies (GWAS) summary statistics for 731 immune cell traits as exposure data, and two GWAS statistics for IS as outcome data. A set of sensitivity analyses, including Cochran's Q test, I 2 statistics, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out sensitivity analyses, were performed to assess the robustness of the results. Additionally, meta-analyses were conducted to combine the results from the two different IS datasets. Finally, we extracted instrumental variables of immune cell traits with causal effects on IS in both IS datasets for SNP annotation., Results: A total of 41 and 35 immune cell traits were identified to have significant causal effects on IS based on two different IS datasets, respectively. Among them, the immune cell trait CD62L - plasmacytoid Dendritic Cell AC and CD4 + CD8 dim T cell%leukocyte respectively served as risk factor and protective element in both IS datasets. The robustness of the causal effects was confirmed through the sensitivity analyses. The results of the meta-analyses further support the causal effects of CD62L - plasmacytoid Dendritic Cell AC (pooled OR=1.030, 95%CI: 1.011-1.049, P =0.002) and CD4 + CD8 dim T cell%leukocyte (pooled OR=0.959, 95%CI: 0.935-0.984, P =0.001). Based on these two immune cell traits, 33 genes that may be related to the causal effects were mapped., Conclusions: Our study demonstrated the potential causal effects of circulating immune cells on IS, providing valuable insights for future studies aimed at preventing IS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Zhang, Li, Duan, Jiang, Gao, Chen and Fang.)

Introduction: Spontaneous cervical artery dissection (sCAD) is a rare vasculopathy whose trigger is still unknown. We hypothesized that autoimmunity against components of the vascular wall might play a critical role in sCAD and examined anti-collagen type I antibodies in patients with sCAD, acute ischemic stroke, patients with thromboendarterectomy, and controls., Methods: Fifty-seven patients with sCAD (age 45.7 ± 10.2 years, female 18 (31.6%)) were prospectively enrolled in four German stroke centers. Blood samples were collected at baseline, at day 10 ± 3, and after 6 ± 1 months. Patients with ischemic stroke not related to CAD (n=54, age 56.7 ± 13.7 years, female 15 (27.8%)), healthy probands (n=80, age 57.4 ± 12.9 years, female 56 (70%)), and patients undergoing thromboendarterectomy of the carotid artery (n=9, age 70.7 ± 9.3 years, female 2 (22.2%)) served as controls. Anti-collagen type I antibodies were determined by enzyme-linked immunosorbent assays (ELISAs)., Results: Patients with acute sCAD had higher serum levels of anti-collagen type I antibodies (33.9 ± 24.6 µg/ml) than probands (18.5 ± 11.0 µg/ml; p <0.001) but lower levels than patients with ischemic stroke not related to sCAD (47.8 ± 28.4 µg/ml; p=0.003). In patients with sCAD, serum levels of anti-collagen type I antibodies were similar in the acute, subacute, and chronic phase. Levels of anti-collagen type I antibodies significantly correlated with circulating collagen type I (rho=0.207, p=0.003)., Conclusion: Anti-collagen type I antibodies seem not to represent a trigger for acute sCAD or ischemic stroke but may rather be linked to the metabolism and turnover of collagen type I., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Zimmermann, Weißenfels, Krümmer, Härtig, Weise, Branzan, Michalski and Pelz.)

Background and Objective: Acute ischemic stroke (AIS) is a leading cause of mortality, severe neurological and long-term disability world-wide. Blood-based indicators may provide valuable information on identified prognostic factors. However, currently, there is still a lack of peripheral blood indicators for the prognosis of AIS. We aimed to identify the most promising prognostic indicators and establish prognostic models for AIS., Methods: 484 subjects enrolled from four centers were analyzed immunophenotypic indicators of peripheral blood by flow cytometry. Least absolute shrinkage and selection operator (LASSO) regression was applied to minimize the potential collinearity and over-fitting of variables measured from the same subject and over-fitting of variables. Univariate and multivariable Cox survival analysis of differences between and within cohorts was performed by log-rank test. The areas under the receiving operating characteristic (ROC) curves were used to evaluate the selection accuracy of immunophenotypic indicators in identifying AIS subjects with survival risk. The prognostic model was constructed using a multivariate Cox model, consisting of 402 subjects as a training cohort and 82 subjects as a testing cohort., Results: In the prospective study, 7 immunophenotypic indicators of distinct significance were screened out of 72 peripheral blood immunophenotypic indicators by LASSO. In multivariate cox regression, CTL (%) [HR: 1.18, 95% CI: 1.03-1.33], monocytes/μl [HR: 1.13, 95% CI: 1.05-1.21], non-classical monocytes/μl [HR: 1.09, 95% CI: 1.02-1.16] and CD56 high NK cells/μl [HR: 1.13, 95% CI: 1.05-1.21] were detected to decrease the survival probability of AIS, while Tregs/μl [HR:0.97, 95% CI: 0.95-0.99, p=0.004], B M /μl [HR:0.90, 95% CI: 0.85-0.95, p=0.023] and CD16 + NK cells/μl [HR:0.93, 95% CI: 0.88-0.98, p=0.034] may have the protective effect. As for indicators' discriminative ability, the AUC for CD56 high NK cells/μl attained the highest of 0.912. In stratification analysis, the survival probability for AIS subjects with a higher level of Tregs/μl, B M /μl, CD16 + NK cells/μl, or lower levels of CD56 high NK cells/μl, CTL (%), non-classical monocytes/μl, Monocytes/μl were more likely to survive after AIS. The multivariate Cox model showed an area under the curve (AUC) of 0.805, 0.781 and 0.819 and 0.961, 0.924 and 0.982 in the training and testing cohort, respectively., Conclusion: Our study identified 7 immunophenotypic indicators in peripheral blood may have great clinical significance in monitoring the prognosis of AIS and provide a convenient and valuable predictive model for AIS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lu, Ni, Yue, Cheng, Du, Li, Tong, Chen and Wang.)

Background: The purpose of this prospective study was to evaluate the association of systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI), with PSCI in patients with acute ischemic stroke (AIS)., Methods: First-onset AIS patients were consecutively included from January 1, 2022 to March 1, 2023. The baseline information was collected at admission. Fasting blood was drawn the next morning. Cognitive function was assessed by the Montreal Cognitive Assessment (MoCA) 3 months after onset. Logistic regression analysis was performed to explore the correlation between SII, SIRI, and PSCI. Receiver operating characteristic (ROC) was conducted to evaluate the predictive ability of SII., Results: 332 participants were recruited, and 193 developed PSCI. Compared with patients without PSCI, the patients with PSCI had higher SII (587.75 (337.42, 988.95) vs. 345.66 (248.44, 572.89), P <0.001) and SIRI (1.59 (0.95, 2.84) vs. 1.02 (0.63, 1.55), P =0.007). SII and SIRI negatively correlated with MoCA scores (both P<0.05). The multivariable logistic regression analysis indicated that SII was independently associated with PSCI ( P <0.001), while SIRI was not. The optimal cutoff for SII to predict PSCI was 676.83×109/L., Conclusions: A higher level of SII upon admission was independently correlated to PSCI three months later in AIS patients.

Ischemic stroke is the leading cause of death and disability worldwide. Nevertheless, there still lacks the effective therapies for ischemic stroke. Microglia are resident macrophages of the central nervous system (CNS) and can initiate immune responses and monitor the microenvironment. Microglia are activated and polarize into proinflammatory or anti‑inflammatory phenotype in response to various brain injuries, including ischemic stroke. Proinflammatory microglia could generate immunomodulatory mediators, containing cytokines and chemokines, these mediators are closely associated with secondary brain damage following ischemic stroke. On the contrary, anti-inflammatory microglia facilitate recovery following stroke. Regulating the activation and the function of microglia is crucial in exploring the novel treatments for ischemic stroke patients. Accumulating studies have revealed that RhoA/ROCK pathway and NF-κB are famous modulators in the process of microglia activation and polarization. Inhibiting these key modulators can promote the polarization of microglia to anti-inflammatory phenotype. In this review, we aimed to provide a comprehensive overview on the role of RhoA/ROCK pathway and NF-κB in the microglia activation and polarization, reveal the relationship between RhoA/ROCK pathway and NF-κB in the pathological process of ischemic stroke. In addition, we likewise discussed the drug modulators targeting microglia polarization., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Emerging evidence suggests that inflammation mediated by the pannexin1 channel contributes significantly to acute ischemic stroke. It is believed that the pannexin1 channel is key in initiating central system inflammation during the early stages of acute ischemic stroke. Moreover, the pannexin1 channel is involved in the inflammatory cascade to maintain the inflammation levels. Specifically, the interaction of pannexin1 channels with ATP-sensitive P2X7 purinoceptors or promotion of potassium efflux mediates the activation of the NLRP3 inflammasome, triggering the release of pro-inflammatory factors such as IL-1 and IL-18, exacerbating and sustaining inflammation of brain. Also, increased release of ATP induced by cerebrovascular injury activates pannexin1 in vascular endothelial cells. This signal directs peripheral leukocytes to migrate into ischemic brain tissue, leading to an expansion of the inflammatory zone. Intervention strategies targeting pannexin1 channels may greatly alleviate inflammation after acute ischemic stroke to improve this patient population's clinical outcomes. In this review, we sought to summarize relevant studies on inflammation mediated by the pannexin1 channel in acute ischemic stroke and discussed the possibility of using brain organoid-on-a-chip technology to screen miRNAs that exclusively target the pannexin1 channel to provide new therapeutic measures for targeted regulation of pannexin1 channel to reduce inflammation in acute ischemic stroke.

The aging of the global population poses significant scientific challenges. Moreover, the biological process of aging is the most significant risk factor for most chronic illnesses; therefore, understanding the molecular and cellular mechanisms underlying these aging-related challenges is crucial for extending the healthy lifespan of older individuals. Preventing brain aging remains a priority public health goal, and integrative and comprehensive aging analyses have revealed that immunosenescence is a potential cause of age-related brain damage and disease (e.g., stroke). Importantly, the neuroinflammatory and immune systems present two-way contact and thus can affect each other. Emerging evidence supports the numerous effects of immunosenescence- and inflammation-mediated immunity in neurologically injured brains. In this study, we briefly outline how aging alters the pathophysiology and transcriptional amplitude in patients who experienced stroke and then discuss how the immune system and its cellular components and molecular mechanisms are affected by age after stroke. Finally, we highlight emerging interventions with the potential to slow down or reduce aging and prevent stroke onset.

The importance of neuroinflammation during the ischemic stroke has been extensively studied. The role of CD4+CD25+ regulatory T (Treg) cells during the recovery phase have shown infarct size reduction and functional improvement, possibly through the mitigation of inflammatory immune responses. We aimed to investigate the molecular factors involved in microglia-Treg cell communication that result in Treg trafficking. First, we observed the migration patterns of CD8+ (cytotoxic) T cells and Treg cells and then searched for chemokines released by activated microglia in an oxygen-glucose deprivation (OGD) model. The transwell migration assay showed increased migration into OGD media for both cell types, in agreement with the increase in chemokines involved in immune cell trafficking from the mouse chemokine profiling array. MSCV retrovirus was transduced to overexpress CCR4 in Treg cells. CCR4-overexpressed Treg cells were injected into the mouse transient middle cerebral artery occlusion (tMCAO) model to evaluate the therapeutic potential via the tetrazolium chloride (TTC) assay and behavioral tests. A general improvement in the prognosis of animals after tMCAO was observed. Our results suggest the increased mobility of CCR4-overexpressed Treg cells in response to microglia-derived chemokines in vitro and the therapeutic potential of Treg cells with increased mobility in cellular therapy., (© 2024. The Author(s).)

Ischemic stroke (IS) is one of the leading causes of death and disability. Complicated mechanisms are involved in the pathogenesis of IS. Immunomodulatory mechanisms are crucial to IS. Acupuncture is a traditional non-drug treatment that has been extensively used to treat IS. The exploration of neuroimmune modulation will broaden the understanding of the mechanisms underlying acupuncture treatment. This review summarizes the immune response of immune cells, immune cytokines, and immune organs after an IS. The immunomodulatory mechanisms of acupuncture treatment on the central nervous system and peripheral immunity, as well as the factors that influence the effects of acupuncture treatment, were summarized. We suggest prospects and future directions for research on immunomodulatory mechanisms of acupuncture treatment for IS based on current progress, and we hope that these will provide inspiration for researchers. Additionally, acupuncture has shown favorable outcomes in the treatment of immune-based nervous system diseases, generating new directions for research on possible targets and treatments for immune-based nervous system diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kuang, Zhu, Chen, Tang and Zhao.)

Precise and efficient regulation of microglia is vital for ischemic stroke therapy and prognosis. The infiltration of neutrophils into the brain provides opportunities for regulatory drugs across the blood-brain barrier, while hindered by neutrophil extracellular traps (NETs) and targeted delivery of intracerebral drugs to microglia. This study reports an efficient neutrophil hijacking nanoplatform (referred to as APTS) for targeted A151 (a telomerase repeat sequence) delivery to microglia without the generation of NETs. In the middle cerebral artery occlusion (MCAO) mouse model, the delivery efficiency to ischemic stroke tissues increases by fourfold. APTS dramatically reduces the formation of NETs by 2.2-fold via reprogramming NETosis to apoptosis in neutrophils via a reactive oxygen species scavenging-mediated citrullinated histone 3 inhibition pathway. Noteworthy, A151 within neutrophils is repackaged into apoptotic bodies following the death pattern reprogramming, which, when engulfed by microglia, polarizes microglia to an anti-inflammatory M2 phenotype. After four times treatment, the cerebral infarction area in the APTS group decreases by 5.1-fold. Thus, APTS provides a feasible, efficient, and practical drug delivery approach for reshaping the immune microenvironment and treating brain disorders in the central nervous system., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Post-stroke neuroinflammation affects the damage and recovery of neurological functions. T cells including CD8 + T cells were present in the ipsilateral hemisphere in the subacute and late phases of ischemic stroke. However, the potential roles of CD8 + T cell subsets in the progression of neuroinflammation have not been characterized. In the current mouse transient middle cerebral artery occlusion model, we investigated the existence of CD8 + T cell subsets in the ipsilateral hemisphere in the subacute and late phases of stroke. We found that ipsilateral CD8 + T cells were present on post-stroke day 3 and increased on post-stroke day 30. The day-3 ipsilateral CD8 + T cells predominantly produced interferon-γ (IFN-γ), while the day-30 ipsilateral CD8 + T cells co-expressed IFN-γ and interleukin-17A (IL-17A). In addition, evaluation of cytokines and transcription factors of the day-30 ipsilateral CD8 + T cells revealed the presence of T cytotoxic 1 (Tc1), T cytotoxic 17 (Tc17), and T cytotoxic 17/1 (Tc17/1) cells. Furthermore, based on the expression of a series of chemokine/cytokine receptors, viable ipsilateral Tc1, Tc17, and Tc17.1 cells were identified and enriched from the day-30 ipsilateral CD8 + T cells, respectively. Co-culture of microglia with ipsilateral Tc1, Tc17, or Tc17.1 cells indicated that the three CD8 + T cell subsets up-regulated the expression of pro-inflammatory mediators by microglia, with Tc17.1 cells being the most potent cell in doing so. Collectively, this study sheds light on the contributions of Tc1, Tc17, and Tc17.1 cells to long-term neuroinflammation after ischemic stroke., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Stroke is a disease with high morbidity, disability, and mortality. Immune factors play a crucial role in the occurrence of ischemic stroke (IS), but their exact mechanism is not clear. This study aims to identify possible immunological mechanisms by recognizing immune-related biomarkers and evaluating the infiltration pattern of immune cells., Methods: We downloaded datasets of IS patients from GEO, applied R language to discover differentially expressed genes, and elucidated their biological functions using GO, KEGG analysis, and GSEA analysis. The hub genes were then obtained using two machine learning algorithms (least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE)) and the immune cell infiltration pattern was revealed by CIBERSORT. Gene-drug target networks and mRNA-miRNA-lncRNA regulatory networks were constructed using Cytoscape. Finally, we used RT-qPCR to validate the hub genes and applied logistic regression methods to build diagnostic models validated with ROC curves., Results: We screened 188 differentially expressed genes whose functional analysis was enriched to multiple immune-related pathways. Six hub genes (ANTXR2, BAZ2B, C5AR1, PDK4, PPIH, and STK3) were identified using LASSO and SVM-RFE. ANTXR2, BAZ2B, C5AR1, PDK4, and STK3 were positively correlated with neutrophils and gamma delta T cells, and negatively correlated with T follicular helper cells and CD8, while PPIH showed the exact opposite trend. Immune infiltration indicated increased activity of monocytes, macrophages M0, neutrophils, and mast cells, and decreased infiltration of T follicular helper cells and CD8 in the IS group. The ceRNA network consisted of 306 miRNA-mRNA interacting pairs and 285 miRNA-lncRNA interacting pairs. RT-qPCR results indicated that the expression levels of BAZ2B, C5AR1, PDK4, and STK3 were significantly increased in patients with IS. Finally, we developed a diagnostic model based on these four genes. The AUC value of the model was verified to be 0.999 in the training set and 0.940 in the validation set., Conclusion: Our research explored the immune-related gene expression modules and provided a specific basis for further study of immunomodulatory therapy of IS., Competing Interests: The authors declare there are no competing interests., (©2024 Cong et al.)

Ischemic stroke (IS) is a common cerebrovascular disease whose pathogenesis involves a variety of immune molecules, immune channels and immune processes. 6-methyladenosine (m6A) modification regulates a variety of immune metabolic and immunopathological processes, but the role of m6A in IS is not yet understood. We downloaded the data set GSE58294 from the GEO database and screened for m6A-regulated differential expression genes. The RF algorithm was selected to screen the m6A key regulatory genes. Clinical prediction models were constructed and validated based on m6A key regulatory genes. IS patients were grouped according to the expression of m6A key regulatory genes, and immune markers of IS were identified based on immune infiltration characteristics and correlation. Finally, we performed functional enrichment, protein interaction network analysis and molecular prediction of the immune biomarkers. We identified a total of 7 differentially expressed genes in the dataset, namely METTL3, WTAP, YWHAG, TRA2A, YTHDF3, LRPPRC and HNRNPA2B1. The random forest algorithm indicated that all 7 genes were m6A key regulatory genes of IS, and the credibility of the above key regulatory genes was verified by constructing a clinical prediction model. Based on the expression of key regulatory genes, we divided IS patients into 2 groups. Based on the expression of the gene LRPPRC and the correlation of immune infiltration under different subgroups, LRPPRC was identified as an immune biomarker for IS. GO enrichment analyses indicate that LRPPRC is associated with a variety of cellular functions. Protein interaction network analysis and molecular prediction indicated that LRPPRC correlates with a variety of immune proteins, and LRPPRC may serve as a target for IS drug therapy. Our findings suggest that LRPPRC is an immune marker for IS. Further analysis based on LRPPRC could elucidate its role in the immune microenvironment of IS., (© 2024. The Author(s).)

Background: Coagulation system is currently known associated with the development of ischemic stroke (IS). Thus, the current study is designed to identify diagnostic value of coagulation genes (CGs) in IS and to explore their role in the immune microenvironment of IS., Methods: Aberrant expressed CGs in IS were input into unsupervised consensus clustering to classify IS subtypes. Meanwhile, key CGs involved in IS were further selected by weighted gene co-expression network analysis (WGCNA) and machine learning methods, including random forest (RF), support vector machine (SVM), generalized linear model (GLM) and extreme-gradient boosting (XGB). The diagnostic performance of key CGs were evaluated by receiver operating characteristic (ROC) curves. At last, quantitative PCR (qPCR) was performed to validate the expressions of key CGs in IS., Results: IS patients were classified into two subtypes with different immune microenvironments by aberrant expressed CGs. Further WGCNA, machine learning methods and ROC curves identified ACTN1, F5, TLN1, JMJD1C and WAS as potential diagnostic biomarkers of IS. In addition, their expressions were significantly correlated with macrophages, neutrophils and/or T cells. GSEA also revealed that those biomarkers may regulate IS via immune and inflammation. Moreover, qPCR verified the expressions of ACTN1, F5 and JMJD1C in IS., Conclusions: The current study identified ACTN1, F5 and JMJD1C as novel coagulation-related biomarkers associated with IS immune microenvironment, which enriches our knowledge of coagulation-mediated pathogenesis of IS and sheds light on next-step in vivo and in vitro experiments to elucidate the relevant molecular mechanisms.

Background and Objective: A correlation between neutrophil extracellular traps (NETs) and ischemic stroke (IS) has been hypothesized, but the results of relevant studies remain controversial. The purpose was to determine whether NETs have an impact on ischemic stroke., Methods: The studies on the correlation between NETs and IS were retrieved from CNKI, Wanfang Data, VIP, CBM, PubMed, Web of Science, Embase, and Cochrane databases by computer from the start of the database to December 2022. The study adhered to PRISMA guidelines. The PICOS model was used to create inclusion criteria. Two researchers screened the literature and extracted the relevant data. The quality of the included studies was evaluated using the NOS and the 11 items recommended by the AHRQ, and meta-analysis was completed using Stata 15.1 software., Results: The researchers included 752 patients in 7 studies (4 case-control studies and 3 cross-sectional studies). The meta-analysis found NETs are positively associated with the severity of IS at the time of onset [r(95% CI) = 0.31(0.24, 0.38), P < 0.001]. NETs are positively associated with a worse prognosis of IS [r(95% CI) = 0.34(0.13, 0.53), P = 0.003]., Conclusion: The presence of NETs is positively related to the severity and prognosis of IS. Higher levels of NETs indicate a more severe disease and a poorer prognosis. Because the number and quality of included studies are limited, the above results must be supported by further high-quality studies., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier: CRD42022356619., (© 2023. The Author(s) under exclusive licence to Belgian Neurological Society.)

Introduction: This study aimed to screen immune-related marker genes of ischemic stroke (IS)., Material and Methods: Two IS-related gene expression datasets were downloaded. The significantly differentially expressed genes (DEGs) and miRNAs (DEMs) between IS and control groups were selected. The differential immune cells were analysed. Weighted gene co-expression network analysis (WGCNA) was applied to analyse immune-related genes, followed by function analysis and interaction network construction. Then, key genes were further screened using optimization algorithm to construct a diagnostic model. Finally, miRNA regulatory network of several key genes was established., Results: In total 321 DEGs and 140 DEMs were obtained. 11 immune cell types were significantly different between IS and control groups. WGCNA identified two key modules, involving 202 differential immune genes. The greenyellow module was enriched in biological processes and pathways associated with T cells, while the midnightblue module was mainly associated with apoptosis, and inflammatory response-related functions and pathways. Protein interaction network identified 10 hub nodes, such as CD8A, ITGAM and TLR4. LASSO regression selected 8 key feature genes, and a risk score model was established. Key model genes were enriched in 63 GO biological processes, such as microglial cell activation, and B cell apoptotic process, and 3 KEGG pathways, such as negative regulation of nuclear cell cycle DNA replication, and hematopoietic cell lineage. Finally, a total of 25 miRNA-target relationship pairs were obtained., Conclusions: This study identified some immune-related marker genes and constructed a diagnostic model based on 8 immune-related genes in IS.

Introduction: Dimethyl fumarate (DMF) has shown potential for protection in various animal models of neurological diseases. However, the impact of DMF on changes in peripheral immune organs and the central nervous system (CNS) immune cell composition after ischemic stroke remains unclear., Methods: Eight-week-old C57BL/6J mice with photothrombosis ischemia and patients with acute ischemic stroke (AIS) were treated with DMF. TTC staining, flow cytometry, and immunofluorescence staining were used to evaluate the infarct volume and changes in immune cells in the periphery and the CNS., Results: DMF reduced the infarct volume on day 1 after PT. DMF reduced the percentages of peripheral immune cells, such as neutrophils, dendritic cells, macrophages, and monocytes, on day 1, followed by NK cells on day 3 and B cells on day 7 after PT. In the CNS, DMF significantly reduced the percentage of monocytes in the brain on day 3 after PT. In addition, DMF increased the number of microglia in the peri-infarct area and reduced the number of neurons in the peri-infarct area in the acute and subacute phases after PT. In AIS patients, B cells decreased in patients receiving alteplase in combination with DMF., Conclusion: DMF can change the immune environment of the periphery and the CNS, reduce infarct volume in the acute phase, promote the recruitment of microglia and preserve neurons in the peri-infarct area after ischemic stroke., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Previous studies investigating innate leukocyte recruitment into the brain after cerebral ischemia have shown conflicting results. Using distinct cell surface and intracellular markers, the current study evaluated the contributions of innate immune cells to the poststroke brain following 1-h middle cerebral artery occlusion (tMCAO) or permanent MCAO (pMCAO), and assessed whether these cells ascribed to an inflammatory state. Moreover, we examined whether there is evidence for leukocyte infiltration into the contralateral (CL) hemisphere despite the absence of stroke infarct. We observed the recruitment of peripheral neutrophils, monocytes and macrophages into the hemisphere ipsilateral (IL) to the ischemic brain infarct at 24 and 96 h following both tMCAO and pMCAO. In addition, we found evidence of increased leukocyte recruitment to the CL hemisphere but to a lesser extent than the IL hemisphere after stroke. Robust production of intracellular cytokines in the innate immune cell types examined was most evident at 24 h after pMCAO. Specifically, brain-associated neutrophils, monocytes and macrophages demonstrated stroke-induced production of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β, while only monocytes and macrophages exhibit a significant expression of arginase 1 (Arg1) after stroke. At 96 h after stroke, brain-resident microglia demonstrated production of TNF-α and IL-1β following both tMCAO and pMCAO. At this later timepoint, neutrophils displayed TNF-α production and brain-associated macrophages exhibited elevation of IL-1β and Arg1 after tMCAO. Further, pMCAO induced significant expression of Arg1 and IL-1β in monocytes and macrophages at 96 h, respectively. These results revealed that brain-associated innate immune cells display various stroke-induced inflammatory states that are dependent on the experimental stroke setting., (© 2022 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

Background: Aging is associated with a chronic low-grade inflammatory state. This condition may affect the acute inflammatory response involved in ST-segment-elevation myocardial infarction (STEMI) or acute ischemic stroke (AIS). We sought to compare the profile of a set of circulating inflammatory markers between young and older patients admitted for STEMI or AIS., Methods: HIBISCUS-STEMI (Cohort of Patients to Identify Biological and Imaging Markers of Cardiovascular Outcomes in ST Elevation Myocardial Infarction) and HIBISCUS-STROKE (Cohort of Patients to Identify Biological and Imaging Markers of Cardiovascular Outcomes in Stroke) are 2 cohort studies that enrolled patients with STEMI treated with primary percutaneous coronary intervention in the cardiac intensive care unit of Lyon and patients with AIS treated with mechanical thrombectomy in the Lyon Stroke Center, respectively from 2016 to 2019. Patients were classified as older if they were ≥65 years and as young if they were <65 years. In both cohorts, CRP (C-reactive protein), IL (interleukin)-6, IL-8, IL-10, MCP (monocyte chemoattractant protein), sTNF-RI (soluble tumor necrosis factor receptor I), sST2 (soluble form suppression of tumorigenicity 2), and VCAM-1 (vascular cellular adhesion molecule-1) were measured on serum collected at 5 time points using enzyme-linked immunosorbent assay. A multiple logistic regression model was performed to detect an association between area under the curve of circulating inflammatory markers within the first 48 hours and older age., Results: A total of 260 patients with STEMI and 164 patients with AIS were included. Of them, there were 76 (29%) and 105 (64%) older patients with STEMI and AIS, respectively. Following multivariable analysis, a high area under the curve of IL-6 and sTNF-RI, a low lymphocyte count, and a high neutrophil-lymphocyte ratio at 24 hours were associated with older age in patients with STEMI and AIS., Conclusions: Older patients had higher IL-6 and sTFN-RI levels within the first 48 hours associated with a lower lymphocyte count and a higher neutrophil-lymphocyte ratio at 24 hours in both cohorts.

Background and Aims: Despite mechanistic data implicating unresolving inflammation in stroke pathogenesis, data regarding circulating immune cell phenotypes - key determinants of inflammation propagation versus resolution - and incident stroke are lacking. Therefore, we aimed to comprehensively define associations of circulating immune phenotypes and activation profiles with incident stroke., Methods: We investigated circulating leukocyte phenotypes and activation profiles with incident adjudicated stroke in 2104 diverse adults from the Multi-Ethnic Study of Atherosclerosis (MESA) followed over a median of 16.6 years. Cryopreserved cells from the MESA baseline examination were thawed and myeloid and lymphoid lineage cell subsets were measured using polychromatic flow cytometry and intracellular cytokine activation staining. We analyzed multivariable-adjusted associations of cell phenotypes, as a proportion of parent cell subsets, with incident stroke (overall) and ischemic stroke using Cox regression models., Results: We observed associations of intermediate monocytes, early-activated CD4 + T cells, and both CD4 + and CD8 + T cells producing interleukin-4 after cytokine stimulation (T h2 and T c2 , respectively) with higher risk for incident stroke; effect sizes ranged from 35% to 62% relative increases in risk for stroke. Meanwhile, differentiated and memory T cell phenotypes were associated with lower risk for incident stroke. In sex-stratified analyses, positive and negative associations were especially strong among men but null among women., Conclusions: Circulating IL-4 producing T cells and intermediate monocytes were significantly associated with incident stroke over nearly two decades of follow-up. These associations were stronger among men and not among women. Further translational studies are warranted to define more precise targets for prognosis and intervention., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Long non-coding RNA small nucleolar RNA host gene 16 (lncRNA SNHG16) is involved in the pathogenesis of acute ischemic stroke (AIS) through the regulation of brain endothelial cell viability, inflammation, atherosclerotic plaque formation, and neural apoptosis. This study aimed to evaluate the prognostic value of lncRNA SNHG16 in AIS patients., Methods: Newly diagnosed AIS patients (N = 120) were serially recruited. Their lncRNA SNHG16 expressions in peripheral blood mononuclear cells (PBMCs) were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR); serum inflammatory cytokines and adhesion molecules were determined using enzyme-linked immunosorbent assay (ELISA). The accumulating recurrence-free survival (RFS) and overall survival (OS) were analyzed. Moreover, controls (N = 60) were recruited and their lncRNA SNHG16 expressions in PBMCs were detected., Results: LncRNA SNHG16 was declined in AIS patients compared to controls (p < 0.001). Moreover, lncRNA SNHG16 was not related to any comorbidities in AIS patients (all p > 0.05). Interestingly, lncRNA SNHG16 was negatively related to tumor necrosis factor alpha (TNF-α) (p < 0.001), interleukin 6 (IL-6) (p = 0.013), and intracellular cell adhesion molecule-1 (ICAM-1) (p = 0.024), while positively correlated with interleukin 10 (IL-10) (p = 0.022) in AIS patients. Besides, lncRNA SNHG16 was inversely associated with the National Institutes of Health Stroke Scale (NIHSS) score in AIS patients (p = 0.003). During the follow-up period, in 14 (11.7%) patients occurred recurrence and 5 (4.2%) patients died. Unexpectedly, lncRNA SNHG16 was not associated with accumulating RFS (p = 0.103) or OS (p = 0.150) in AIS patients., Conclusion: LncRNA SNHG16 relates to lower inflammatory cytokines, adhesion molecules, and milder disease severity, but fails to predict prognosis in AIS patients., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)