Microglia gene-expression after a transient ischemic attack (TIA)
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ORGANISM(S): Mus musculus
PROVIDER: GSE312513 | GEO | 2026/02/13
REPOSITORIES: GEO
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Project description:Microglia gene-expression after a transient ischemic attack (TIA)
| PRJNA1374083 | ENA
Project description:Background: Transient ischemic attack (TIA) induces ischemic tolerance that can reduce the subsequent ischemic damage and improve prognosis of stroke patients. However, the underlying mechanisms remain elusive. Recent advances in plasma metabolomics analysis have made it a powerful tool to investigate human pathophysiological phenotypes and mechanisms of diseases. In this study, we aimed to identify the bioactive metabolites from the plasma of TIA patients for determination of their prophylactic and therapeutic effects on protection against cerebral ischemic stroke, and the mechanism of TIA-induced ischemic tolerance against subsequent stroke. Methods: Metabolomic profiling using liquid chromatography-mass spectrometry was performed to identify the TIA-induced differential bioactive metabolites in the plasma samples of 20 patients at day 1 (time for basal metabolites) and day 7 (time for established chronic ischemic tolerance-associated metabolites) after onset of TIA. Mouse MCAO-induced stroke model was used to verify their prophylactic and therapeutic potentials. Transcriptomics changes in circulating neutrophils of TIA patients were determined by RNA-sequencing. Multivariate statistics and integrative analysis of metabolomics and transcriptomics were performed to elucidate the potential mechanism of TIA-induced ischemic tolerance. Findings: Plasma metabolomics analysis identified five differentially upregulated metabolites associated with TIA-induced ischemic tolerance, namely all-trans 13,14 dihydroretinol (atDR), 20-carboxyleukotriene B4, prostaglandin B2, cortisol and 9-KODE. They were associated with the metabolic pathways of retinol, arachidonic acid, and neuroactive ligand-receptor interaction. Prophylactic treatment of MCAO mice with these five metabolites significantly improved neurological functions. Additionally, post-stroke treatment with atDR or 9-KODE significantly reduced the cerebral infarct size and enhanced sensorimotor functions, demonstrating the therapeutic potential of these bioactive metabolites. Mechanistically, we found in TIA patients that these metabolites were positively correlated with circulating neutrophil counts. Integrative analysis of plasma metabolomics and neutrophil transcriptomics further revealed that TIA-induced metabolites are significantly correlated with specific gene expression in circulating neutrophils which showed prominent enrichment in FoxO signaling pathway and upregulation of the anti-inflammatory cytokine IL-10. Finally, we demonstrated that the protective effect of atDR-pretreatment on MCAO mice was abolished when circulating neutrophils were depleted. Interpretation: TIA-induced ischemic tolerance is associated with upregulation of plasma bioactive metabolites which can protect against cerebral ischemic damage and improve neurological functions through a positive role of circulating neutrophils.
2023-11-15 | GSE241280 | GEO
Project description:This data set shows dramatic changes in gene expression in microglia isolated from C57Bl6/J mice subjected to transient middle cerebral artery occlusion, as compared to those subjected to sham surgery. Mice deficient in Mincle (Clec4e-/-) showed significantly improved injury outcomes 3 and 7 days after transient middle cerebral artery occlusion. However, when comparing changes in gene expression in microglia 24 hours after blood reperfusion, there were no differences between wild-type and Clec4e-/- mice, indicating that Mincle does not participate in early microglial activation. Wild type and Mincle knock-out (Clec4e-/-) mice. After 1 h of transient middle cerebral artery occlusion (tMCAO) and 24 h of reperfusion, mice were perfused with PBS, their brains dissected, and 2 ipsilesional hemispheres (with cerebellum and brainstem removed) pooled for microglia isolation. For sham-operated animals, the whole forebrain was used and brains were not pooled. After myelin separation by Percoll gradient centrifugation, around 80,000 CD45intermediate, CD11b+ microglial cells were sorted from each sample. Sham samples n=3, tMCAO samples n=5.
2016-03-24 | E-GEOD-77986 | biostudies-arrayexpress
Project description:BackgroundPrompt treatment following Transient Ischemic Attack (TIA) can reduce the risk of subsequent stroke and disability. However, many patients delay in making contact with medical services. This study aimed to explore TIA patients' accounts of delay between symptom onset and contacting medical services including how decisions to contact services were made and the factors discussed in relation to delay.MethodsTwenty interviews were conducted with TIA patients in England. Using a previous systematic review as an initial framework, interview data were organised into categories of symptom recognition, presence of others and type of care sought. A thematic analysis was then conducted to explore descriptions of care-seeking relevant to each category.ResultsDelay in contacting medical services varied from less than an hour to eight days. Awareness of typical stroke symptoms could lead to urgent action when more severe TIA symptoms were present but could lead to delay when experienced symptoms were less severe. The role of friends and family varied widely from deciding on and enacting care-seeking decisions to simply providing transport to the GP practice. When family or friends played a greater role, and both made and enacted care-seeking decisions, delays were often shorter, even when patients themselves failed to identify symptoms. Healthcare professionals also impacted on patients' care-seeking with greater delays in seeking further care for the same episode described when patients perceived a lack of urgency during initial healthcare interactions.ConclusionsThis study provides new information on patients' decisions to contact medical services following TIA and identifies overlapping factors that can lead to delay in receiving appropriate treatment. While recognition of symptoms may contribute to delay in contacting medical services, additional factors, including full responsibility being taken by others and initial healthcare interactions, can over-ride or undermine the importance of patients' own identification of TIA.
| S-EPMC4138063 | biostudies-literature
Project description:Microglia are resident CNS immune cells that are active sensors in healthy brain and versatile effectors under pathological conditions. Cerebral ischemia induces a robust neuroinflammatory response that includes marked changes in the gene expression and phenotypic profile of a variety of endogenous CNS cell types (astrocytes, neurons, microglia) as well as an influx of leukocytic cells (neutrophils, macrophages, T-cells) from the periphery. Many molecules and conditions can trigger a transformation of ârestingâ (or surveying) microglia to an âactivatedâ (alerted/reactive) state. Here we review recent developments in the literature that relate to microglial activation in the experimental setting of in vitro and in vivo ischemia. We also present new data from our own laboratory demonstrating the direct effects of in vitro ischemic conditions on the microglial phenotype and genomic profile. Emphasis is placed on the role of specific molecular signaling systems such as hypoxia inducible factor-1 (HIF-1) and toll-like receptor-4 (TLR4) in regulating the microglial response in this setting. We then review histological and recent novel radiological data that confirms a key role for microglial activation in the setting of ischemic stroke in humans. We discuss recent progress in the pharmacological and molecular targeting of microglia in acute ischemic stroke. Finally, we explore how recent studies on ischemic preconditioning have increased interest in preemptively targeting microglial activation in order to reduce stroke severity. 12 arrays, 4 experimental groups, 3 replicates in each group, CN is control normoxia, CH is control hypoxia, TN is TLR4 knockout normoxia, TH is TLR4 knockout hypoxia.
2010-10-05 | E-GEOD-18602 | biostudies-arrayexpress
Project description:Recent work has highlighted that people who have had TIA may have abnormal motor and cognitive function. We aimed to quantify deficits in a cohort of individuals who had TIA and measured changes in their abilities to perform behavioural tasks over 1 year of follow-up using the Kinarm Exoskeleton robot. We additionally considered performance and change over time in an active control cohort of migraineurs. Individuals who had TIA or migraine completed 8 behavioural tasks that assessed cognition as well as motor and sensory functionality in the arm. Participants in the TIA cohort were assessed at 2, 6, 12, and 52 weeks after symptom resolution. Migraineurs were assessed at 2 and 52 weeks after symptom resolution. We measured overall performance on each task using an aggregate metric called Task Score and quantified any significant change in performance including the potential influence of learning. We recruited 48 individuals to the TIA cohort and 28 individuals to the migraine cohort. Individuals in both groups displayed impairments on robotic tasks within 2 weeks of symptom cessation and also at approximately 1 year after symptom cessation, most commonly in tests of cognitive-motor integration. Up to 51.3% of people in the TIA cohort demonstrated an impairment on a given task within 2-weeks of symptom resolution, and up to 27.3% had an impairment after 1 year. In the migraine group, these numbers were 37.5% and 31.6%, respectively. We identified that up to 18% of participants in the TIA group, and up to 10% in the migraine group, displayed impairments that persisted for up to 1 year after symptom resolution. Finally, we determined that a subset of both cohorts (25-30%) experienced statistically significant deteriorations in performance after 1 year. People who have experienced transient neurological symptoms, such as those that arise from TIA or migraine, may continue to experience lasting neurological impairments. Most individuals had relatively stable task performance over time, with some impairments persisting for up to 1 year. However, some individuals demonstrated substantial changes in performance, which highlights the heterogeneity of these neurological disorders. These findings demonstrate the need to consider factors that contribute to lasting neurological impairment, approaches that could be developed to alleviate the lasting effects of TIA or migraine, and the need to consider individual neurological status, even following transient neurological symptoms.
| S-EPMC8382836 | biostudies-literature
Project description:BackgroundThe Community of Practice (CoP) model represents one approach to address knowledge management to support effective implementation of best practices.ObjectiveWe sought to identify CoP developmental strategies within the context of a national quality improvement project focused on improving the quality for patients receiving acute transient ischemic attack (TIA) care.DesignStepped wedge trial.ParticipantsMultidisciplinary staff at six Veterans Affairs medical facilities.InterventionsTo encourage site implementation of a multi-component quality improvement intervention, the trial included strategies to improve the development of a CoP: site kickoff meetings, CoP conference calls, and an interactive website (the "Hub").ApproachMixed-methods evaluation included data collected through a CoP attendance log; semi-structured interviews with site participants at 6 months (n = 32) and 12 months (n = 30), and CoP call facilitators (n = 2); and 22 CoP call debriefings.Key resultsThe critical seeding structures that supported the cultivation of the CoP were the kickoffs which fostered relationships (key to the community element of CoPs) and provided the evidence base relevant to TIA care (key to the domain element of CoPs). The Hub provided the forum for sharing quality improvement plans and other tools which were further highlighted during the CoP calls (key to the practice element of CoPs). CoP calls were curated to create a positive context around participants' work by recognizing team successes. In addition to improving care at their local facilities, the community created a shared set of tools which built on their collective knowledge and could be shared within and outside the group.ConclusionsThe PREVENT CoP advanced the mission of the learning healthcare system by successfully providing a forum for shared learning. The CoP was grown through seeding structures that included kickoffs, CoP calls, and the Hub. A CoP expands upon the learning collaborative implementation strategy as an effective implementation practice.
| S-EPMC7878647 | biostudies-literature
Project description:BackgroundPatients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease.MethodsIn this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction.ResultsBy 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P=0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P=0.003).ConclusionsIn this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.).
| S-EPMC4887756 | biostudies-literature
Project description: Not available
| S-EPMC3134717 | biostudies-literature
Project description:We used a robotic exoskeleton to quantify specific patterns of abnormal upper limb motor behaviour in people who have had transient ischemic attack (TIA). A cohort of people with TIA was recruited within two weeks of symptom onset. All individuals completed a robotic-based assessment of 8 behavioural tasks related to upper limb motor and proprioceptive function, as well as cognitive function. Robotic task performance was compared to a large cohort of controls without neurological impairments corrected for the influence of age. Impairment in people with TIA was defined as performance below the 5th percentile of controls. Participants with TIA were also assessed with the National Institutes of Health Stroke Scale (NIHSS) score, Chedoke-McMaster Stroke Assessment (CMSA) of the arm, the Behavioural Inattention Test (BIT), the Purdue pegboard test (PPB), and the Montreal Cognitive Assessment (MoCA). Age-related white matter change (ARWMC), prior infarction and cella-media index (CMI) were assessed from baseline CT scan that was performed within 24 hours of TIA. Acute infarction was assessed from diffusion-weighted imaging in a subset of people with TIA. Twenty-two people with TIA were assessed. Robotic assessment showed impaired upper limb motor function in 7/22 people with TIA patients and upper limb sensory impairment in 4/22 individuals. Cognitive tasks involving robotic assessment of the upper limb were completed in 13 participants, of whom 8 (61.5%) showed significant impairment. Abnormal performance in the CMSA arm inventory was present in 12/22 (54.5%) participants. ARWMC was 11.8 ± 6.4 and CMI was 5.4 ± 1.5. DWI was positive in 0 participants. Quantitative robotic assessment showed that people who have had a TIA display a spectrum of upper limb motor and sensory performance deficits as well as cognitive function deficits despite resolution of symptoms and no evidence of tissue infarction.
| S-EPMC5741219 | biostudies-literature