Augmentation of peripheral lymphocyte-derived cholinergic activity in patients with acute ischemic stroke.
Ontology highlight
ABSTRACT:
SUBMITTER: Yuan M
PROVIDER: S-EPMC6792255 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
Publications
Augmentation of peripheral lymphocyte-derived cholinergic activity in patients with acute ischemic stroke.
Yuan Meng M Han Bin B Xia Yiping Y Liu Ye Y Wang Chunyang C Zhang Chao C
BMC neurology 20191015 1
<h4>Background</h4>Brain ischemia activates the parasympathetic cholinergic pathway in animal models of human disease. However, it remains unknown whether activation of the cholinergic pathway impacts immune defenses and disease outcomes in patients with ischemic stroke. This study investigated a possible association between peripheral cholinergic activity, post-stroke infection, and mortality.<h4>Methods</h4>In this study, we enrolled 458 patients with acute ischemic stroke (< 24 h after onset) ...[more]
Similar Datasets
Project description:Background and Aims: Systemic inflammation is associated with an increased risk of cognitive impairment and dementia, but the associations between them in stroke patients are less clear. We examined the impact of systemic inflammation represented as the neutrophil-lymphocyte ratio (NLR) on the development of post-stroke cognitive impairment (PSCI) and domain-specific cognitive outcomes 3-month after ischemic stroke. Methods: Using prospective stroke registry data, we consecutively enrolled 345 participants with ischemic stroke whose cognitive functions were evaluated 3-month after stroke. Their cognition was assessed with the Korean version of the Vascular Cognitive Impairment Harmonization Standards and the Korean-Mini Mental Status Examination. PSCI was defined as a z-score of < -2 standard deviations for age, sex, and education adjusted means in at least one cognitive domain. The participants were categorized into five groups according to the quintiles of NLR (lowest NLR, Q1). The cross-sectional association between NLR and PSCI was assessed using multiple logistic regression, adjusting for age, sex, education, vascular risk factors, and stroke type. Results: A total of 345 patients were enrolled. The mean age was 63.0 years and the median NIHSS score and NLR were 2 [1-4] and 2.26 [1.65-2.91], respectively. PSCI was identified in 71 (20.6%) patients. NLR was a significant predictor for PSCI both as a continuous variable (adjusted OR, 1.14; 95% CI, 1.00-1.31) and as a categorical variable (Q5, adjusted OR, 3.26; 95% CI, 1.17-9.08). Patients in the Q5 group (NLR ≥ 3.80) showed significantly worse performance in global cognition and in visuospatial and memory domains. Conclusions: NLR in the acute stage of ischemic stroke was independently associated with PSCI at 3 months after stroke, and high NLR was specifically associated with cognitive dysfunction in the memory and visuospatial domains. Thus, systemic inflammation may be a modifiable risk factor that may influence cognitive outcomes after stroke.
| S-EPMC8280279 | biostudies-literature
Project description:The association between vasomotor tone of the peripheral arteries and cerebral hemisphere function has not been established. This study analyzed the peripheral vasoreactivity of patients with acute ischemic stroke and hemiplegia using a modified Raynaud scan, which is a new technology for blood flow measurement. In this retrospective case-control study, we examined patients with unilateral weakness consistent with ischemic lesions who underwent brain magnetic resonance imaging and modified Raynaud scanning within five days from the onset of symptoms. The modified Raynaud scan was used to quantify the radioactivity of the bilateral fingertips during rest and cooling-heating thermal stress conditions and estimate vasoreactivity based on the change in the blood amount per time under rest-thermal stress. The subjects were classified into the preserved and impaired groups based on their degrees of vasomotor reaction. Based on the modified Raynaud scanning, 37 (mean age = 69.1 ± 10.6) and 32 (mean age = 62.6 ± 11.8) subjects were allocated to the preserved and impaired groups, respectively. Binary logistic regression showed that the affected limb edema (odds ratio (OR) 6.15; confidence interval (CI) 1.40-26.97; p = 0.016) and anterior circulation (OR 3.68; CI 1.01-13.48; p = 0.049) were associated with impaired vasoreactivity. The modified Raynaud scans confirmed that central lesions in the anterior circulation with hemiparesis may influence the vasoreactivity of edematous peripheral arteries. These results may inform treatment and rehabilitation for stroke patients with hemiparesis.
| S-EPMC8058338 | biostudies-literature
Project description:Acute ischemic stroke (AIS) is a primary cause of mortality and morbidity worldwide. Currently, no clinically approved immune intervention is available for AIS treatment, partly due to the lack of relevant patient classification based on the peripheral immunity status of patients with AIS. In this study, we adopted the consensus clustering approach to classify patients with AIS into molecular subgroups based on the transcriptomic profiles of peripheral blood, and we identified three distinct AIS molecular subgroups and 8 modules in each subgroup by the weighted gene co-expression network analysis. Remarkably, the pre-ranked gene set enrichment analysis revealed that the co-expression modules with subgroup I-specific signature genes significantly overlapped with the differentially expressed genes in AIS patients with hemorrhagic transformation (HT). With respect to subgroup II, exclusively male patients with decreased proteasome activity were identified. Intriguingly, the majority of subgroup III was composed of female patients who showed a comparatively lower level of AIS-induced immunosuppression (AIIS). In addition, we discovered a non-linear relationship between female age and subgroup-specific gene expression, suggesting a gender- and age-dependent alteration of peripheral immunity. Taken together, our novel AIS classification approach could facilitate immunomodulatory therapies, including the administration of gender-specific therapeutics, and attenuation of the risk of HT and AIIS after ischemic stroke.
| S-EPMC9388856 | biostudies-literature
Project description:Stroke is one of the major causes of death and long-term disability, of which acute ischemic stroke (AIS) is the most common type. Although circRNA expression profiles of AIS patients have been reported to be significantly altered in blood and peripheral blood mononuclear cells, the role of exosome-contained circRNAs after AIS is still unknown. Plasma exosomes from ten AIS patients and ten controls were isolated, and through microarray and bioinformatics analysis, profile and putative function of circRNAs in the plasma exosomes were studied. A total of 198 circRNAs were differentially quantified (|log2 FoldChange|≥1.00, P<0.05) between AIS patients and controls.The functions of host genes of differentially quantified circRNAs, including RNA and protein process, focal adhesion and leukocyte transendothelial migration, were associated with the development of AIS. As miRNA sponge, differentially quantified circRNAs had the potential to regulate pathways related to AIS, like PI3K-Akt, AMPK and chemokine pathways. Of 198 differentially quantified circRNAs, 96 circRNAs possessing strong translational ability could affect cellular structure and activity, like focal adhesion, tight junction and endocytosis. Most differentially quantified circRNAs were predicted to bind to EIF4A3 and AGO2- two RNA binding proteins (RBPs)- and play a role in AIS. In conclusion, plasma exosome-derived circRNAs were significantly differentially quantified between AIS patients and controls, and participated in the occurrence and progression of AIS by sponging miRNA/RBPs or translating into proteins, indicating that circRNAs from plasma exosomes could be crucial molecules in the pathogenesis of AIS and promising candidates as diagnostic biomarkers and therapeutic targets for the condition.
2022-01-28 | GSE195442 | GEO
Project description:BackgroundThe immune response to acute ischemic stroke (AIS) is implicated in diagnosis, prognosis, and intervention; however, the temporal dynamics of leukocytes following AIS are poorly understood. The purpose of this study was to characterize peripheral leukocyte dynamics following AIS among individuals with poor and favorable outcomes.MethodsA retrospective chart review was conducted among patients with a diagnosis of AIS who were treated at a comprehensive stroke center across a 3-year timeframe. Groups were defined according to stroke outcomes. Patients with poor outcomes were distinguished from those with favorable outcomes by discharge National Institute of Health Stroke Score, infarct size, and Modified Rankin Scale. Leukocyte counts were compared among controls and AIS outcome groups.ResultsThe neutrophil-lymphocyte ratio (NLR) calculated at 48-72 h post-AIS was identified as the strongest predictor of outcome. NLR was significantly higher in the poor outcome group (8.68 ± 0.93) compared with both the favorable outcome (4.5 ± 0.51, p = 0.009) and control group (4.33 ± 0.66, p < 0.001). Patients with a 48-72 h NLR ≥ 4.58 were 5.58 times more likely to have a poor outcome than AIS patients with an NLR < 4.58.ConclusionsThe results of this study improve the understanding of the immune response in AIS. Low neutrophil count relative to high lymphocyte count at 48-72 h post-AIS should be considered a predictor of a favorable stroke outcome. Conversely, high neutrophil count relative to low lymphocyte count at 48-72 h post-AIS should be considered a predictor of a poor stroke outcome.
| S-EPMC7898194 | biostudies-literature
Project description:Background Both inflammation and thrombotic/hemostatic mechanisms may play a role in acute ischemic stroke (AIS) pathogenesis, and a biomarker, such as the platelet-to-lymphocyte ratio (PLR), considering both mechanisms may be of clinical utility. Objectives This meta-analysis sought to examine the effect of PLR on functional outcomes, early neurological changes, bleeding complications, mortality, and adverse outcomes in AIS patients treated with reperfusion therapy (RT). Design Systematic Review and Meta-Analysis Data Sources and Methods Individual studies were retrieved from the PubMed/Medline, EMBASE and Cochrane databases. References thereof were also consulted. Data were extracted using a standardised data sheet, and systematic reviews and meta-analyses on the association of admission (pre-RT) or delayed (post-RT) PLR with defined clinical and safety outcomes were conducted. In the case of multiple delayed PLR timepoints, the timepoint closest to 24 hours was selected. Results Eighteen studies (n=4878) were identified for the systematic review, of which 14 (n=4413) were included in the meta-analyses. PLR collected at admission was significantly negatively associated with 90-day good functional outcomes (SMD=−.32; 95% CI = −.58 to −.05; P=.020; z=−2.328), as was PLR collected at delayed timepoints (SMD=−.43; 95% CI = −.54 to −.32; P<.0001; z=−7.454). PLR at delayed timepoints was also significantly negatively associated with ENI (SMD=−.18; 95% CI = −.29 to −.08; P=.001. Conversely, the study suggested that a higher PLR at delayed timepoints may be associated with radiological bleeding and mortality. The results varied based on the type of RT administered. Conclusions A higher PLR is associated with worse outcomes after stroke in terms of morbidity, mortality, and safety outcomes after stroke.
| S-EPMC9290168 | biostudies-literature
Project description: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.
| S-EPMC11246473 | biostudies-literature
Project description:Background and purposeTo investigate the association of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) with post-thrombolysis early neurological outcomes including early neurological improvement (ENI) and early neurological deterioration (END) in patients with acute ischemic stroke (AIS).MethodsAIS patients undergoing intravenous thrombolysis were enrolled from April 2016 to September 2019. Blood cell counts were sampled before thrombolysis. Post-thrombolysis END was defined as the National Institutes of Health Stroke Scale (NIHSS) score increase of ≥ 4 within 24 h after thrombolysis. Post-thrombolysis ENI was defined as NIHSS score decrease of ≥ 4 or complete recovery within 24 h. Multinomial logistic regression analysis was performed to explore the relationship of NLR, PLR, and LMR to post-thrombolysis END and ENI. We also used receiver operating characteristic curve analysis to assess the discriminative ability of three ratios in predicting END and ENI.ResultsAmong 1060 recruited patients, a total of 193 (18.2%) were diagnosed with END and 398 (37.5%) were diagnosed with ENI. Multinomial logistic model indicated that NLR (odds ratio [OR], 1.385; 95% confidence interval [CI] 1.238-1.551, P = 0.001), PLR (OR, 1.013; 95% CI 1.009-1.016, P = 0.001), and LMR (OR, 0.680; 95% CI 0.560-0.825, P = 0.001) were independent factors for post-thrombolysis END. Moreover, NLR (OR, 0.713; 95% CI 0.643-0.791, P = 0.001) served as an independent factor for post-thrombolysis ENI. Area under curve (AUC) of NLR, PLR, and LMR to discriminate END were 0.763, 0.703, and 0.551, respectively. AUC of NLR, PLR, and LMR to discriminate ENI were 0.695, 0.530, and 0.547, respectively.ConclusionsNLR, PLR, and LMR were associated with post-thrombolysis END. NLR and PLR may predict post-thrombolysis END. NLR was related to post-thrombolysis ENI.
| S-EPMC7896410 | biostudies-literature
Project description:Platelets play a crucial role in the pathogenesis of stroke and antiplatelet agents exist for its treatment and prevention. Through the use of LC-MS based protein expression profiling, platelets from stroke patients were analyzed and then correlated with the proteomic analyses results in the context of this disease. This study was based on patients who post ischemic stroke were admitted to hospital and had venous blood drawn within 24 hrs of the incidence. Label-free protein expression analyses of the platelets' tryptic digest was performed in triplicate on a UPLC-ESI-qTOF-MS/MS system and ProteinLynx Global Server (v2.5, Waters) was used for tandem mass data extraction. The peptide sequences were searched against the reviewed homo sapiens database (www.uniprot.org) and the quantitation of protein variation was achieved through Progenesis LC-MS software (V4.0, Nonlinear Dynamics). These Label-free differential proteomics analysis of platelets ensured that 500 proteins were identified and 83 of these proteins were found to be statistically significant. The differentially expressed proteins are involved in various processes such as inflammatory response, cellular movement, immune cell trafficking, cell-to-cell signaling and interaction, hematological system development and function and nucleic acid metabolism. The expressions of myeloperoxidase, arachidonate 12-Lipoxygenase and histidine-rich glycoprotein are involved in cellular metabolic processes, crk-like protein and ras homolog gene family member A involved in cell signaling with vitronectin, thrombospondin 1, Integrin alpha 2b, and integrin beta 3 involved in cell adhesion. Apolipoprotein H, immunoglobulin heavy constant gamma 1 and immunoglobulin heavy constant gamma 3 are involved in structural, apolipoprotein A-I, and alpha-1-microglobulin/bikunin precursor is involved in transport, complement component 3 and clusterin is involved in immunity proteins as has been discussed. Our data provides an insight into the proteins that are involved in the platelets' activation response during ischemic stroke. It could be argued that this study lays the foundation for future mechanistic studies.
| S-EPMC4919045 | biostudies-literature
Project description:Studies assessing the prognostic effect of inflammatory markers of blood cells on the outcomes of patients with acute ischemic stroke treated with endovascular treatment (EVT) are sparse. We evaluated whether the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) affect reperfusion status in patients receiving EVT. Using a multicenter registry database, 282 patients treated with EVT were enrolled in this study. The primary outcome measure was unsuccessful reperfusion rate after EVT defined by thrombolysis in cerebral infarction grades 0-2a. Logistic regression analysis was performed to analyze the association between NLR/PLR and unsuccessful reperfusion rate after EVT. Both NLR and PLR were higher in the unsuccessful reperfusion group than in the successful reperfusion group (p < 0.001). Multivariate analysis showed that both NLR and PLR were significantly associated with unsuccessful reperfusion (adjusted odds ratio (95% confidence interval): 1.11 (1.04-1.19), PLR: 1.004 (1.001-1.01)). The receiver operating characteristic curve showed that the predictive ability of both NLR and PLR was close to good (area under the curve (AUC) of NLR: 0.63, 95% CI (0.54-0.72), p < 0.001; AUC of PLR: 0.65, 95% CI (0.57-0.73), p < 0.001). The cutoff values of NLR and PLR were 6.2 and 103.6 for unsuccessful reperfusion, respectively. Higher NLR and PLR were associated with unsuccessful reperfusion after EVT. The combined application of both biomarkers could be useful for predicting outcomes after EVT.
| S-EPMC8399654 | biostudies-literature