RNA sequencing analysis Reveal Post-Stroke Cognitive Impairment related genes in Hippocampus of Cerebral Ischemic Rat
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ABSTRACT:
ORGANISM(S): Hippocampus
PROVIDER: GSE160290 | GEO | 2022/10/27
REPOSITORIES: GEO
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Project description:This program addresses the gene signature associated with brain (cortex) in the tMCAO rat model for stroke. The tMCAO stroke model profiling data was analyzed by identifying genes that were up- and down-regulated at selected p value and fold change in brain cortex of the Sprague Dawley rats following middle cerebral artery occlusion compared to the sham-operated controls.
2013-03-22 | E-GEOD-38037 | biostudies-arrayexpress
Project description:Background. Women account for 60% of all stroke deaths and are more often permanently disabled than men, despite their higher observed stroke incidence. Considering the clinical population affected by stroke, an obvious drawback is that many pre-clinical and clinical studies only investigate young males. To improve therapeutic translation from bench to bedside, we believe that it is advantageous to include both sexes in experimental models of stroke. The aims of this study were to identify early cerebral vascular responses to ischemic stroke in females, compare the differential gene expression patterns with those seen in males, and identify potential new therapeutic targets. Results. Transient middle cerebral artery occlusion (tMCAO) was used to induce stroke in both female and male rats, the middle cerebral arteries (MCAs) were isolated 3 hours post reperfusion and RNA was extracted. Affymetrix whole transcriptome expression profiling was performed on female (n = 12) MCAs to reveal differentially expressed genes. In total, 1076 genes had an increased expression and 879 genes a decreased expression in the occluded MCAs as compared with the control MCAs from female rats. An enrichment of genes related to apoptosis, regulation of transcription, protein autophosphorylation, inflammation, oxidative stress, and tissue repair and recovery were seen in the occluded MCA. The high expression genes chosen for qPCR verification (Adamts4, Olr1, JunB, Fosl1, Serpine1, S1pr3, Ccl2 and Socs3) were all shown to be upregulated in the same manner in both females and males after tMCAO (p < 0.05; n = 23). When comparing the differentially expressed genes in female MCAs (occluded and non-occluded) with our previous findings in males after tMCAO, a total of 297 genes overlapped (all groups had 32 genes in common). Conclusions. The cascades of processes initiated in the vasculature following reperfusion are complex. Dynamic gene expression alterations were observed in the occluded MCAs, and to a less pronounced degree in the non-occluded MCAs. Dysregulation of inflammation and blood-brain barrier breakdown are possible pharmacological targets. The sample of genes (<1% of differentially expressed genes) validated for this microarray did not reveal any sex differences.
2020-11-25 | GSE162072 | GEO
Project description:To detect mRNAs in ischemic stroke animals we dissected contralateral (CL) and peri-ischemic (PI) cortex of transient middle cerebral artery occlusion (tMCAo) mice wild-type and ciRS-7 KO We performed differentially expression analysis of RNA-seq of wild-type and ciRS-7 KO tMCAo ischemic mice
2023-01-31 | GSE213177 | GEO
Project description:Ischemic stroke is a common acute CNS disorder leading to nearly half a million deaths per year in Europe. The high mortality is primarily owed to the limited treatment options of restoring blood flow in a narrow time window of several hours. Furthermore, inflammatory processes in the days and weeks after ischemic stroke contribute to tissue loss and neurological deficits. The key cells that influence and control this inflammatory cascade are microglia, the innate immune cells of the CNS. Microglia can be influenced and activated by e.g. lipopolysaccharide (LPS),a bacterial cell membrane component. It has been previously shown, that repetitive LPS stimuli prior to infarction (termed immunological preconditioning) lead to reduced infarct volumina in mouse models of ischemic stroke. Furthermore, our laboratory has shown, that phosphoinositide-3 kinase gamma mediates microglial functions after LPS-preconditioning. Hence, the aim of this work was to characterize proteomic alterations in microglia with (I) ischemic stroke in general in the tMCAO (transient middle cerebral artery occlusion) mouse model of ischemic stroke, (II) the influence of LPS-preconditioning on microglial proteomic alterations after tMCAO and (III) the role of PI3Ky in the microglial proteomic changes after tMCAO and preconditioning. This was done by a single LPS injection 3 days before tMCAO in wildtype mice and mice with PI3Ky knockout or knockin of the kinase dead form of PI3Ky.
2024-03-22 | PXD031930 | Pride
Project description:In this study, we focused on microglia in the central nervous system and analyzed microglia in mouse models of tMCAO.
2024-08-01 | GSE269173 | GEO
Project description:Background and objectivesPost-stroke cognitive impairment (PSCI) occurs in up to 50% of patients with acute ischemic stroke (AIS). Thus, the prediction of cognitive outcomes in AIS may be useful for treatment decisions. This PSCI cohort study aimed to determine the applicability of a machine learning approach for predicting PSCI after stroke.MethodsThis retrospective study used a prospective PSCI cohort of patients with AIS. Demographic features, clinical characteristics, and brain imaging variables previously known to be associated with PSCI were included in the analysis. The primary outcome was PSCI at 3-6 months, defined as an adjusted z-score of less than - 2.0 standard deviation in at least one of the four cognitive domains (memory, executive/frontal, visuospatial, and language), using the Korean version of the Vascular Cognitive Impairment Harmonization Standards-Neuropsychological Protocol (VCIHS-NP). We developed four machine learning models (logistic regression, support vector machine, extreme gradient boost, and artificial neural network) and compared their accuracies for outcome variables.ResultsA total of 951 patients (mean age 65.7 ± 11.9; male 61.5%) with AIS were included in this study. The area under the curve for the extreme gradient boost and the artificial neural network was the highest (0.7919 and 0.7365, respectively) among the four models for predicting PSCI according to the VCIHS-NP definition. The most important features for predicting PSCI include the presence of cortical infarcts, mesial temporal lobe atrophy, initial stroke severity, stroke history, and strategic lesion infarcts.ConclusionOur findings indicate that machine-learning algorithms, particularly the extreme gradient boost and the artificial neural network models, can best predict cognitive outcomes after ischemic stroke.
| S-EPMC10468853 | biostudies-literature
Project description:CD45high infiltrating immune cells were sorted from ischemic mouse brains at 5 days (5d) and 14 days (14d) after transient (60 min) middle cerebral artery occlusion (tMCAO) and subjected to scRNAseq.
2021-05-19 | GSE171169 | GEO
Project description:The impact of serum matrix metalloproteinases-9 (MMP-9) on cognitive impairment after ischemic stroke is unclear. We aimed to investigate the association between serum MMP-9 in the short-term acute phase of ischemic stroke and cognitive impairment at 3 months. Our study was based on a subsample from the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke); a total of 558 patients with serum MMP-9 levels from 7 of 26 participating sites of the trial were included in this analysis. Cognitive impairment severity was categorized as severe, mild, or none (Mini-Mental State Examination score, <23, 23-26, or ≥27, respectively; Montreal Cognitive Assessment score, <20, 20-24, or ≥25, respectively). Cognitive impairment was defined as a score of <27 for Mini-Mental State Examination or <25 for Montreal Cognitive Assessment. According to Mini-Mental State Examination score, 143 participants (25.6%) had mild cognitive impairment and 153 (27.4%) had severe cognitive impairment at 3 months. After adjustment for age, National Institutes of Health stroke score, education, and other covariates, the odds ratio for the highest quartile of serum MMP-9 compared with the lowest quartile was 3.20 (95% confidence interval, 1.87-5.49) for cognitive impairment. Multiple-adjusted spline regression model showed a linear association between MMP-9 levels and cognitive impairment (P<0.001 for linearity). Sensitivity and subgroup analyses further confirmed these results. Similar significant findings were observed when cognitive impairment was defined by Montreal Cognitive Assessment score. Increased serum MMP-9 levels in the short-term phase of ischemic stroke were associated with 3-month cognitive impairment, independently of established risk factors.
| S-EPMC5778973 | biostudies-literature
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:Background:Oxidative damage may contribute to post-stroke cognitive impairment (PSCI), but the underlying mechanisms are not fully elucidated. Dimethyl fumarate (DMF) has been used as an antioxidant in multiple sclerosis and psoriasis patients. We hypothesized that redox state was associated with PSCI, and DMF might exert neuroprotective effect against PSCI via anti-oxidative actions. Methods:To confirm this hypothesis, we first conducted a clinical study (NCT03519828) that enrolled patients diagnosed with acute ischemic stroke within 48 hours. Data were analyzed based on demographic characteristics, disease history, clinical data and redox state. Logistic regression was used to identify the factors associated with PSCI. Next, a middle cerebral artery occlusion (MCAO) rat model was used to explore the antioxidant capacity and neuroprotective effect of DMF. Furthermore, behavioural experiments, histology and immunostaining, and transmission electron microscopy were also performed. Results:Higher baseline NIHSS score, lower GSH/GSSG and T-AOC levels were found in the PSCI patients. Better performance in Morris water maze and shuttle box testing, more regular arranged neurons and Nissl bodies, less TUNEL-positive cells and autophagosomes, lower expression of 4-HNE, and higher expression of GCLM and NQO1 were found in the (DMF + MCAO) rats compared with the MCAO rats. Conclusions:These findings suggest that DMF may alleviate PSCI via neuroprotective actions, providing a new therapeutic strategy for PSCI.
| S-EPMC7186746 | biostudies-literature