Pathogenesis Of Ischemic Stroke Research Articles

The clinical value of serum xanthine oxidase levels in patients with acute ischemic stroke

Xanthine oxidase (XO), a form of xanthine oxidoreductase, is widely distributed in various human tissues. As a major source for the generation of superoxide radicals, XO is involved in the induction of oxidative stress and inflammation during ischemic and hypoxic tissue injury. Therefore, we designed this study to identify the role of serum XO levels in acute ischemic stroke (AIS) pathogenesis. In this single-center prospective study, 328 consecutive patients with AIS for the first time were included, and 107 age- and sex-matched healthy controls from a community-based stroke screening population were also included. The serum levels of XO and several conventional stroke risk factors were assessed. Multivariate analysis was applied to evaluate the relationship between serum levels of XO and clinical outcomes, and nomogram models were developed to predict the onset, progression and prognosis of AIS. Compared with the healthy control group, the serum level of XO was significantly higher in the AIS group (P < 0.05) and was an independent risk factor for AIS (OR 8.68, 95% CI 4.62–14.33, P < 0.05). Patients with progressive stroke or a poor prognosis had a much higher serum level of XO than patients with stable stroke or a good prognosis (all P < 0.05). In addition, the serum level of XO was an independent risk factor for stroke progression (OR 1.98, 95% CI 1.12–3.50, P = 0.018) and a poor prognosis (OR 2.51, 95% CI 1.47–3.31, P = 0.001). The nomogram models including XO to predict the onset, progression and prognosis of AIS had good prediction and differentiation abilities. The findings of this study show that the serum level of XO on admission was an independent risk factor for AIS and had certain clinical predictive value for stroke progression and prognosis in patients with AIS.

Assessment of Changes in Serum C-Reactive Protein Levels in Patients after Ischemic Stroke Undergoing Rehabilitation-A Retrospective Observational Study.

Inflammation plays a key role in the pathogenesis and prognosis of ischemic stroke. C-reactive protein (CRP) is an inflammatory biomarker of inflammation and may reflect the progression of vascular disease. Using a biomarker such as CRP to predict recovery rather than mortality may present clinical value in providing rehabilitation. The primary aim of the study was to analyze changes in serum CRP levels in patients after ischemic stroke during the regenerative-compensatory period and to assess the usefulness of CRP as a potential biomarker during the rehabilitation period. The project was carried out as a retrospective analysis of prospectively collected data from post-stroke patients from the Department of Neurological Rehabilitation of the Regional Specialist Hospital in Wrocław. A group of 52 patients, after their first-ever ischemic stroke with subsequent hemiplegia, was finally qualified to participate in the study. Serum CRP levels were determined during blood laboratory tests. The Modified Rankin Scale (mRS) and Barthel Index (BI) were used to assess functional outcomes. Rehabilitation using neurophysiological methods was applied five days a week (each session lasted 60 min, and the entire period was 42 days). At the first test, serum CRP levels were found to be above 5 mg/L in 19 patients, the second test in 12 patients, the third test in five patients, and the fourth test in 9 patients. Only three patients had values higher than 5 mg/L in all consecutive assessments (p > 0.05). There was a statistically significant increase in BI scores after therapy (p < 0.001) as well as a decrease in the mRS score by 2.2 points (p < 0.001), in CRP values by 5.02 mg/L (p = 0.019), and in cortisol levels by 2.5 nmol/L (p = 0.002). Statistically significant relationships were observed between the CRP levels after rehabilitation and the corresponding mRS scores (rs = 0.29, p = 0.038). Furthermore, the effect of BMI on CRP levels was demonstrated (B = 0.20, p = 0.038). In conclusion, despite demonstrating a significant relationship between CRP levels and corresponding mRS scores, CRP levels alone may not serve as an independent predictor of long-term functional outcomes in ischemic stroke patients undergoing rehabilitation.

An Updated Review of Mitochondrial Transplantation as a Potential Therapeutic Strategy Against Cerebral Ischemia and Cerebral Ischemia/Reperfusion Injury.

Regardless of the progress made in the pathogenesis of ischemic stroke, it remains a leading cause of adult disability and death. To date, the most effective treatment for ischemic stroke is the timely recanalization of the occluded artery. However, the short time window and reperfusion injury have greatly limited its application and efficacy. Mitochondrial dysfunction and ATP depletion have become regarded as being hallmarks of neuropathophysiology following ischemic stroke. Mitochondrial transplantation is a novel potential therapeutic intervention for ischemic stroke that has sparked widespread concern during the past few years. This review summarizes and discusses the effects of mitochondrial transplantation in in vitro and in vivo ischemic stroke models. In addition, pharmacological interventions promoting mitochondrial transplantation are reviewed and discussed. We also discuss the potential challenges to the clinical application of mitochondrial transplantation in the treatment of ischemic stroke.

Advances in the study of the pathogenesis of ischemic stroke

Ischemic stroke is a common neurological disease with the characteristics of high morbidity, high mortality and high recurrence, and its pathogenesis has been one of the hot spots of research. In recent years, with the continuous development of neuroscience and biomedical research methods, a lot of progress has been made in the study of the pathogenesis of ischemic stroke. This paper reviews the literature on the pathogenesis of ischemic stroke at home and abroad in recent years, and summarizes the pathophysiological changes involved in the development of ischemic stroke and the risk factors that may lead to its occurrence and progression, to better understand the pathogenesis of ischemic stroke and provide more effective means for its prevention and treatment.

Role of Platelet to Lymphocyte Ratio, Neutrophil to Lymphocyte Ratio and Lymphocyte to Monocyte Ratio in Acute Ischaemic Stroke Severity: A Prospective Cohort Study

Introduction: Stroke is one of the leading causes of mortality and morbidity worldwide, with ischaemic stroke being the most common . Inflammation plays a key role in the pathogenesis of ischaemic stroke and the tissue injury that occurs poststroke, leading to stroke severity. Aim: To assess whether the Neutrophil to Lymphocyte Ratio (NLR), Lymphocyte to Monocyte Ratio (LMR), and Platelet to Lymphocyte Ratio (PLR) ratios correlate with the severity of ischaemic stroke in acute ischaemic stroke cases. Materials and Methods: This was a prospective cohort study conducted at KR Hospital, Mysore, Karnataka, India from July 2021 to June 2022, wherein 106 ischaemic stroke cases presenting within 24 hours of symptom onset were assessed, and the outcomes at discharge or at the end of one week were noted. Routine investigations and Non Contrast Computed Tomography (NCCT) brain scans were performed at the time of admission. National Institute of Health Stroke Scale (NIHSS) scoring was conducted at admission, and patients were grouped into mild to moderate stroke (&lt;16) and severe stroke (≥16) categories. The values of PLR, NLR, and LMR were calculated from the blood routine performed at admission. The data was entered into Microsoft Excel and analysed using Statistical Package for the Social Sciences (SPSS) 25.0 software. A p-value of &lt;0.05 was considered statistically significant. Results: The mean age in this study was 62.67±14.225 years, of which the majority 76 (71.7%) were males. Co-morbidities included hypertension 53 (50%), diabetes 26 (24%), previous history of stroke 13 (12.3%), chronic alcohol consumption 44 (41.5%), and smoking 47 (44.3%) within the study population, and no significant association was found with stroke severity. Approximately 17% presented with severe stroke, while 83% presented with mild to moderate stroke. The total count in the mild to moderate stroke (&lt;16) group was 10.5345±3.91 103 /mm3 and in the severe stroke group (≥16), it was 15.445±10.27 103 /mm3 . In the mild to moderate stroke group (&lt;16), the mean NLR, PLR, and LMR were 5.93±5.16, 179.79±120.72, and 6.14±6.98, respectively. In the severe stroke group (≥16), the mean NLR, PLR, and LMR were 13.83±24.62, 175.1±89.20, and 3.96±3.89, respectively. Conclusion: The PLR, NLR, and LMR ratios can be used to assess the severity of stroke cases, especially in resourcelimited settings.

Identification of disulfidptosis-related genes and analysis of immune infiltration characteristics in ischemic strokes.

Immune infiltration plays a pivotal role in the pathogenesis of ischemic stroke. A novel form of cell death known as disulfidptosis has emerged in recent studies. However, there is currently a lack of research investigating the regulatory mechanism of disulfidptosis-related genes in immune infiltration during ischemic stroke. Using machine learning methods, we identified candidate key disulfidptosis-related genes (DRGs). Subsequently, we performed an analysis of immune cell infiltration to investigate the dysregulation of immune cells in the context of ischemic stroke. We assessed their diagnostic value by employing receiver operating characteristic (ROC) curves. To gain further insights, we conducted functional enrichment analyses to elucidate the signaling pathways associated with these seven DRGs. We identified two distinct subclusters based on the expression patterns of these seven DRGs. The unique roles of these subclusters were further evaluated through KEGG analysis and immune infiltration studies. Furthermore, we validated the expression profiles of these seven DRGs using both single-cell datasets and external datasets. Lastly, molecular docking was performed to explore potential drugs for the treatment of ischemic stroke. We identified seven DRGs. The seven DRGs are related to immune cells. Additionally, these seven DRGs also demonstrate potential diagnostic value in ischemic stroke. Functional enrichment analysis highlighted pathways such as platelet aggregation and platelet activation. Two subclusters related to disulfidptosis were defined, and functional enrichment analysis of their differentially expressed genes (DEGs) primarily involved pathways like cytokine-cytokine receptor interaction. Single-cell analysis indicated that these seven DRGs were primarily distributed among immune cell types. Molecular docking results suggested that genistein might be a potential therapeutic drug. This study has opened up new avenues for exploring the causes of ischemic stroke and developing potential therapeutic targets.

Genetic Variants Associated with High Susceptibility of Premature Ischemic Stroke.

Several polymorphisms had been associated with an increased risk of ischemic stroke, but results are inconclusive. The aim of this study was to examine the association between AGTR1 A1166C and TSP-1 N700S polymorphisms and ischemic stroke in a young Mexican population. In a case-control study, 250 patients ≤ 45 years of age with ischemic stroke and 250 controls matched by age and gender were included. The polymorphisms were determined in all participants by polymerase chain reaction. There were statistical differences in genotype distribution (p = 0.01) and allele frequency (p = 0.001) of AGTR1 A1166C polymorphism. In contrast, there was a similar genotype distribution (p = 0.96) and allele frequency (p = 0.76) of the TSP1 N700S genetic variant between groups. Hypertension (p = 0.03), smoking (p = 0.02), and family history of atherothrombotic disease (p = 0.04) were associated with stroke, but not diabetes (p = 0.30) and dyslipidemia (p = 0.08). This is the first study in Mexican population to explore several genetic variants in young patients with ischemic stroke. Our results suggest that polymorphisms in the renin-angiotensin-aldosterone system could contribute to premature hypertension, endothelial dysfunction, atherothrombosis, vasoconstriction, smooth muscle cell migration, and proliferation. In contrast, polymorphisms in the coagulation factors are not associated with ischemic stroke. Environmental factors such as diabetes and dyslipidemia could be less important in the pathogenesis of ischemic stroke at a young age. We suggest that those polymorphisms should be determined in individuals with a family history of thrombosis to avoid the stroke development. Therefore, genotype-environmental combination could determine several possible phenotypes at different moments in life.

Oxidative stress in the pathogenesis of stroke and its correction

We reviewed the role of oxidative stress (OS) in the pathogenesis of ischemic (IS) and hemorrhagic stroke (HS). OS plays a major role in programmed cell death, increased permeability of the blood-brain barrier, astroglial and microglial activation, and local inflammatory response. We also reviewed the current state of neuro- and cytoprotection studies and their translation in clinical practice. With respect to experimental and clinical data the efficacy of long term administration of multimodal cytoprotective drug with antioxidant effect - ethylmethylhydroxypyridine succinate (Mexidol) is discussed during the acute and early recovery period after stroke.

Association of Long Non-Coding RNA Malat1 with Serum Levels of Interleukin-1 Beta and Vitamin D in Patients with Ischemic Stroke.

Previous studies have demonstrated the strong association of inflammatory cytokines and vitamin D (VitD) deficiency and ischemic stroke (IS) pathogenesis. Due to the negative correlation between long non-coding RNA (lncRNA) Malat1 and pro-inflammatory factors we decided to investigate the associations between Malat1 expression with serum interleukin-1β (IL-1β), and VitD levels in IS patients. In this cross-sectional study, 63 IS patients were included. We used enzyme-linked immunosorbent assays to evaluate the serum levels of VitD and IL-1β. Malat1 expression was evaluated by the real-time polymerase chain reaction test. The associations between Malat1expression with VitD and IL-1β were analysed with linear regression (Stepwise model) and Pearson's correlation analysis. The Malat1 expression was inversely correlated with stroke severity (r=-0.25, P=0.043). Stepwise regression analysis showed a significant positive relationship between VitD level and Malat1 expression (Beta=0.28, P=0.02), and also showed a non-significant negative relationship between IL-1β and stroke severity. VitD level showed a positive Pearson correlation with Malat1 (r=0.28, P=0.023) and a negative correlation with IL-1β (r=-0.29, P=0.018) while it could not detect a significantly negative correlation with stroke severity. For the first time the associations between Malat1 expression with IL-1β and VitD in IS patients was analyzed. We found a significant positive relationship between VitD and Malat1. This correlation needs to be investigated with a larger sample size to achieve a strong and reliable association between VitD and Malat1.

Identification of immunogenic cell death-related gene classification patterns and immune infiltration characterization in ischemic stroke based on machine learning.

Ischemic stroke (IS) accounts for more than 80% of strokes and is one of the leading causes of death and disability in the world. Due to the narrow time window for treatment and the frequent occurrence of severe bleeding, patients benefit less from early intravenous thrombolytic drug therapy. Therefore, there is an urgent need to explore the molecular mechanisms poststroke to drive the development of new therapeutic approaches. Immunogenic cell death (ICD) is a type of regulatory cell death (RCD) that is sufficient to activate the adaptive immune response of immunocompetent hosts. Although there is growing evidence that ICD regulation of immune responses and immune responses plays an important role in the development of IS, the role of ICD in the pathogenesis of IS has rarely been explored. In this study, we systematically evaluated ICD-related genes in IS. The expression profiles of ICD-related genes in IS and normal control samples were systematically explored. We conducted consensus clustering, immune infiltration analysis, and functional enrichment analysis of IS samples using ICD differentially expressed genes. The results showed that IS patients could be classified into two clusters and that the immune infiltration profile was altered in different clusters. In addition, we performed machine learning to screen nine signature genes that can be used to predict the occurrence of disease. We also constructed nomogram models based on the nine risk genes (CASP1, CASP8, ENTPD1, FOXP3, HSP90AA1, IFNA1, IL1R1, MYD88, and NT5E) and explored the immune infiltration correlation, gene-miRNA, and gene-TF regulatory network of the nine risk genes. Our study may provide a valuable reference for further elucidation of the pathogenesis of IS and provide directions for drug screening, personalized therapy, and immunotherapy for IS.

Features of pathogenesis and risk factors of in-hospital ischemic stroke

In-hospital ischemic stroke (IHIS) is one of the most critical competing diseases that can develop in patients during inpatient treatment. Causes associated with diagnostic and therapeutic measures may play an additional role in the pathogenesis of IHIS, in addition to traditional risk factors. Objective : to study the pathogenesis features and assess risk factors for IHIS. Patients and methods . The comorbidity, main and additional risk factors of IHIS in patients of therapeutic (n=112; 44.3%), surgical (n=125; 49.4%) and neurological (n=16; 6.3%) profiles were studied. Results and discussion . The proportion of perioperative stroke in the study was 37.2%. The frequency of atherothrombotic, cardioembolic, and lacunar subtypes of IHIS did not differ in groups of patients of different profiles. In the group of surgical patients, the proportion of strokes of another established etiology was 24.8% and was higher than in therapeutic (9.8%; p&lt;0.05) and neurological (6.25%; p&lt;0.005) patients. The proportion of strokes of unknown etiology in the group of surgical patients, on the contrary, was lower (15.2%) than in patients with therapeutic (35.7%; p&lt;0.05) and neurological (50.0%; p&lt;0.05) profile. An additional risk factor for IHIS for non-surgical patients was insufficient antithrombotic prophylaxis, for surgical patients – surgery. Conclusion . Compared with out-of-hospital ischemic stroke, the causes of in-hospital ischemic stroke are more diverse and cannot always be explained solely by the higher comorbidity of hospitalized patients. The TOAST classification of ischemic stroke subtypes does not fully reflect the pathogenesis of IHIS, as it does not take into account the possibility of external influences, especially in cases where it is not possible to establish the exact cause of stroke, and the most likely trigger is medical intervention.

Identification of immune characteristic landscapes related to autophagy in ischemic stroke.

Ischemic stroke (IS) is a common and grievous nervous system disease. Both autophagy activation and immune response after cerebral ischemia play important roles in the development of IS. Many studies have revealed a close interplay between autophagy and immunity. However, little is known about how autophagy influences the immune characteristics of IS. Hence, the study aims to systematically explore the role of autophagy and its impact on immune characteristics in IS. We first compared the expression differences of autophagy genes in a training set and identified 20 dysregulated autophagy genes between healthy and IS samples. An autophagy-related classifier composed of seven genes was further established and could well distinguish healthy and IS samples. Then, the association between autophagy and immune characteristics, including infiltrating immunocytes, activity of immune reactions, and HLA gene expression, was investigated. The results showed that autophagy closely correlated with immune characteristics, such as NAMPT and ARNT significantly related to infiltrating immunocytes; PPP1R15A and CASP3 significantly related to activity of immune reactions; and NAMPT and ATG16L2 significantly related to HLA genes. Next, two distinct autophagy expression patterns were identified by unsupervised clustering analysis, and diverse immune characteristics were discovered between them. A total of 5481 autophagy phenotype-related genes were obtained between two expression patterns, and their biological functions revealed that these genes were involved in immune-related biological pathways. Finally, five dysregulated autophagy genes (FOS, MAP1LC3B, ERO1L, ARNT, and PPP1R15A) were proved between IS and healthy samples using another two validation sets. Our results illustrated that autophagy had a dramatic effect on the immunity of IS and provided a novel sight into understanding the pathogenesis of IS.

CYP4 subfamily V member 2 (CYP4V2) polymorphisms were associated with ischemic stroke in Chinese Han population

BackgroundCYP4 subfamily V member 2 (CYP4V2) polymorphisms are related to venous thromboembolism. However, the influence of CYP4V2 polymorphisms on the susceptibility to ischemic stroke (IS) remains undetermined.MethodsWe selected and genotyped five polymorphisms of CYP4V2 in 575 cases and 575 controls to test whether CYP4V2 variants were associated with the risk for IS in a Chinese Han population. Genotyping of CYP4V2 polymorphisms was performed using the Agena MassARRAY platform. Logistic regression analysis was used to assess the association between CYP4V2 polymorphisms and IS risk by calculating odds ratios (ORs) and 95% confidence interval (CI). False-positive report probability analysis was applied to assess the noteworthy relationship of the significant findings.ResultsCYP4V2 rs1398007 might be a risk factor for IS (OR = 1.34, 95% CI 1.05–1.71, p = 0.009). Specially, confounding factors (age, gender, smoking and drinking status) might affect the relationship between rs1398007 and IS susceptibility. Moreover, rs1053094 and rs56413992 were associated with IS risk in males. Multifactor dimensionality reduction analysis showed the combination of rs13146272 and rs3736455 had the strongest interaction effect (information gain value of 0.40%). Furthermore, genotypes of rs1398007 (p = 0.006) and rs1053094 (p = 0.044) were associated with the levels of high-density lipoprotein cholesterol (HDL-C) among healthy controls.ConclusionOur results first provided evidence that CYP4V2 rs1398007 might be a risk factor for IS, which provides instructive clues for studying the mechanisms of CYP4V2 to the pathogenesis of IS.

Leukocyte Count and Neutrophil-To-Lymphocyte Ratio as Simple Hematologic Predictors of Stroke Severity and Functional Outcome in Acute Ischemic Stroke Patients

Background: It has long been recognized that inflammation plays a critical role in the pathogenesis of ischemic stroke. However, whether leukocyte count and neutrophil-to-lymphocyte ratio are related to stroke severity and functional outcome is uncertain. Objective: This clinical study aimed to evaluate the association of leukocyte count and neutrophil-to-lymphocyte ratio with stroke severity and functional outcome in acute ischemic stroke patients. Methods: This hospital-based, retrospective observational study included 112 subjects with acute ischemic stroke. All subjects had their demographic, clinical, and laboratory data obtained. The leukocyte count and neutrophil-to-lymphocyte ratio were evaluated by stroke severity on admission and 3-month functional outcome. The severity of stroke at admission was measured using the National Institutes of Health Stroke Scale (NIHSS), whereas the Barthel Index was used to measure 3-month functional outcome (BI). We conducted a regression analysis, adjusting for any confounding variables. Results: Higher leukocyte count was significantly associated with increased risk of stroke severity (odds ratio [OR] 1.391, 95% confidence intervals [CI], 1.121-1.725, p: 0.003) and unfavorable functional outcome (OR 1.434, 95% CI, 1.068-1.925, p: 0.017). Higher neutrophil-to-lymphocyte ratio was not significantly associated with increased risk of stroke severity (OR 1.181, 95% CI, 0.947-1.474, p: 0.140) and unfavorable functional outcome (OR 1.246, 95% CI, 0.905-1.716, p: 0.177). Conclusion: Our study indicates that leukocyte count is an independent predictor of stroke severity on admission and unfavorable functional outcome.

Impact of miR-200b and miR-495 variants on the risk of large-artery atherosclerosis stroke.

Single-nucleotide polymorphisms (SNPs) of microRNAs (miRNAs) may alter miRNA transcription, maturation and target specificity, thus affecting stroke susceptibility. We aimed to investigate whether miR-200b and miR-495 SNPs may be associated with ischemic stroke (IS) risk and further explore underlying mechanisms including related genes and pathways. MiR-200b rs7549819 and miR-495 rs2281611 polymorphisms were genotyped among 712 large-artery atherosclerosis (LAA) stroke patients and 1,076 controls in a case-control study. Bioinformatic analyses were performed to explore potential association of miR-200b/495 with IS and to examine the effects of these two SNPs on miR-200b/495. Furthermore, we evaluated the association between these two SNPs and stroke using the public GWAS datasets. In our case-control study, rs7549819 was significantly associated with a decreased risk of LAA stroke (OR = 0.73, 95% CI = 0.58-0.92; p = 0.007), while rs2281611 had no significant association with LAA stroke risk. These results were consistent with the findings in East Asians from the GIGASTROKE study. Combined effects analysis revealed that individuals with 2-4 protective alleles (miR-200bC and miR-495T) exhibited lower risk of LAA stroke than those with 0-1 variants (OR = 0.76, 95% CI = 0.61-0.96; p = 0.021). Bioinformatic analyses showed that miR-200b and miR-495 were significantly associated with genes and pathways related to IS pathogenesis, and rs7549819 and rs2281611 markedly influenced miRNA expression and structure. MiR-200b rs7549819 polymorphism and the combined genotypes of miR-200b rs7549819 and miR-495 rs2281611 polymorphisms were associated with decreased risk of LAA stroke in Chinese population.

Purinergic signaling: a potential therapeutic target for ischemic stroke.

Pathogenesis of ischemic stroke is mainly characterized by thrombosis and neuroinflammation. Purinergic signaling pathway constitutes adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine (ADO). ATP is hydrolyzed to ADP and then to AMP by extracellular nucleotidase CD39; AMP is subsequently converted to adenosine by CD73. All these nucleotides and nucleosides act on purinergic receptors protecting against thrombosis and inhibit inflammation. In addition, many physical methods have been found to play a neuroprotective role through purinergic signaling. This review mainly introduces the role and potential mechanism of purinergic signalings in the treatment of ischemic stroke, so as to provide reference for seeking new treatment methods for stroke.

Genetic polymorphisms of MiR-499a (rs3746444) and MiR-196a2 (rs11614913) in ischemic stroke and correlation with risk factors

miRNAs have functional roles in ischemic stroke through regulating their target genes. The present study aimed to assess the association between the genetic polymorphisms of miR-499a A>G (rs3746444) and miR-196a2 T>C (rs11614913) and the risk factors of ischemic stroke.With respect to miR-499a A>G, the AG genotype was associated with an increased risk of ischemic stroke (p = 0.01). However, the AA genotype had a significant protective role for ischemic stroke among females (p = 0.03). No significant association was found between different genotypes and such risk factors as diabetes mellitus, hypertension, and aging.The TT genotype of miR-196a2 T>C had a significant protective role (OR = 0.4, 95 % CI = 0.2–0.9, p = 0.02). Additionally, the CC genotype and C allele of miR-196a2 T > C significantly increased the risk of ischemic stroke (OR = 2.4, 95 % CI = 1.3–4.5, p = 0.005 and OR = 1.9, 95 % CI = 1.3–3.01, p = 0.001, respectively). However, the inheritance of C allele had a protective role against diabetes (p = 0.01). No association was observed between the miR-196a2 genotypes and hypertension, gender, and age.The association between both miR-499a and miR-196a2 genetic polymorphisms and the pathogenesis of ischemic stroke indicated that these polymorphisms could be used as potential biomarkers for the susceptibility of ischemic stroke.

Gut Microbiota in Ischemic Stroke: Role of Gut Bacteria-Derived Metabolites.

Ischemic stroke (IS) remains a leading cause of death and long-term disability globally. Several mechanisms including glutamate excitotoxicity, calcium overload, neuroinflammation, oxidative stress, mitochondrial damage, and apoptosis are known to be involved in the pathogenesis of IS, but the underlying pathophysiology mechanisms of IS are not fully clarified. During the past decade, gut microbiota were recognized as a key regulator to affect the health of the host either directly or via their metabolites. Recent studies indicate that gut bacterial dysbiosis is closely related to hypertension, diabetes, obesity, dyslipidemia, and metabolic syndrome, which are the main risk factors for cardiovascular diseases. Increasing evidence indicates that IS can lead to perturbation in gut microbiota and increased permeability of the gut mucosa, known as "leaky gut," resulting in endotoxemia and bacterial translocation. In turn, gut dysbiosis and impaired intestinal permeability can alter gut bacterial metabolite signaling profile from the gut to the brain. Microbiota-derived products and metabolites, such as short-chain fatty acids (SCFAs), bile acids (BAs), trimethylamine N-oxide (TMAO), lipopolysaccharides (LPS), and phenylacetylglutamine (PAGln) can exert beneficial or detrimental effects on various extraintestinal organs, including the brain, liver, and heart. These metabolites have been increasingly acknowledged as biomarkers and mediators of IS. However, the specific role of the gut bacterial metabolites in the context of stroke remains incompletely understood. In-depth studies on these products and metabolites may provide new insight for the development of novel therapeutics for IS.

Adenomyosis-Associated Ischemic Stroke: Pathophysiology, Detection and Management

Female-specific risk factors for stroke have gradually received attention. The relationship between ischemic stroke and adenomyosis, a benign uterine disorder commonly present in parous women, is underrecognized. We aimed to provide an overview of the epidemiology, pathophysiological mechanisms, clinical characteristics, diagnostic considerations, and potential therapeutic strategies of adenomyosis-associated ischemic stroke. We shared our experience with the diagnosis and management of a patient, and summarized current findings and knowledge gaps of this disease based on previous literature. The relevant studies were searched in English and Chinese databases up to April 2022 using the keywords “ischemic stroke”, “cerebral infarction” and “adenomyosis”. Then, we provided a narrative review of the retrieved articles. Finally, the data of 32 cases were analyzed. We found that increased levels of carbohydrate antigen 125 and D-dimer and decreased level of hemoglobin are biomarkers of adenomyosis-associated ischemic stroke. In addition, hypercoagulability might be a key mechanism leading to thromboembolism in the cerebrovascular system. Additional studies are needed to find optimal prevention strategies for the disease. A better understanding of this “rare” pathogenesis of ischemic stroke may inform a more precise diagnosis and effective prevention strategy in middle-aged women with embolic stroke of undetermined source.

Atrial Cardiomyopathy and Cryptogenic Stroke

Background The frequency of cryptogenic stroke (CS) is about 30% of all cases of ischemic stroke (IS). Patients with CS represent a heterogeneous group of patients and require an individualized approach to antithrombotic therapy for secondary prevention. The frequency of development of repeated acute cerebrovascular events in patients with CS is 4.5% per year, which exceeds this indicator in patients with an established pathogenetic variant of IS. Until recently, the dominant point of view, suggesting that the main cause of CS is paroxysmal atrial fibrillation (AF) and for the secondary prevention of IS in this cohort of patients, oral anticoagulants may be more effective than antiplatelet agents, has not been confirmed. The causal relationship between IS and AF is currently not fully understood. Apparently, AF serves as a marker of atrial cardiomyopathy, which is the direct cause of IS. Aim of study Raising the awareness of neurologists about the causes, pathogenetic mechanisms of development and methods for diagnosing IS in patients with atrial cardiomyopathy. Material and methods To achieve this aim, the results of scientific studies on atrial cardiomyopathy as a risk factor for CS were analyzed. The literature search was carried out in electronic search systems Scopus, eLibrary, PubMed using the keywords: ischemic stroke, cryptogenic stroke, atrial cardiomyopathy, pathogenesis of ischemic stroke. Scientific articles published between 1957 and 2021 were selected to be analyzed. And 36% of the analyzed papers on the topic of CS were published no more than 5 years ago. Conclusion The cumulative evidence suggests that atrial fibrillation is not the only cause of embolic events in patients with evidence of atrial dysfunction. Atrial cardiomyopathy can be the cause of thromboembolic syndrome and cryptogenic stroke, even in the absence of atrial fibrillation, therefore, the latter should be considered as a common manifestation of the underlying atrial cardiomyopathy. Since the majority of cardiac thrombi in patients with atrial fibrillation originate in the left atrium, it is likely that patients with atrial cardiomyopathy and cryptogenic stroke represent a group of patients who may be indicated for anticoagulant therapy as a secondary prevention of ischemic stroke and systemic embolism. However, this hypothesis needs to be confirmed.