Stroke-induced transcriptomic alterations in mouse cerebral microvessels
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE221379 | GEO | 2022/12/24
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: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:Stroke-induced transcriptomic alterations in mouse cerebral microvessels
| PRJNA914210 | ENA
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:We aimed to investigate the influence of ischemic stroke in mice on their ribosomal mRNA in astrocytes. Therefore, we make use of the conditional Cre/LoxP System in the RiboTag mouse line in order to isolate the ribosomal mRNA of astrocytes. CreERT2 expression under the astrocyte-specific Cx43 promoter is induced by Tamoxifen injection and activates the expression of a haemagglutinin tag on ribosomal proteins. 3 weeks after Tamoxifen induction, mice were subjected to a 60 min middle cerebral artery occlusion (tMCAO), which is an established ischemic stroke model. Control mice were not further treated.
2019-02-22 | GSE103781 | GEO
Project description:We aimed to investigate the influence of ischemic stroke in mice on their ribosomal mRNA in astrocytes. Therefore, we make use of the conditional Cre/LoxP System in the RiboTag mouse line in order to isolate the ribosomal mRNA of astrocytes. CreERT2 expression under the astrocyte-specific Cx43 promoter is induced by Tamoxifen injection and activates the expression of a haemagglutinin tag on ribosomal proteins. 3 weeks after Tamoxifen induction, mice were subjected to a 60 min middle cerebral artery occlusion (tMCAO), which is an established ischemic stroke model. Control mice were not further treated.
2019-02-22 | GSE103782 | GEO
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:A filtration method followed by microarray analyses allows PDE components to be identified in brain microvessels, and confirmed that PDE4D and PDE5A are the primary forms expressed in rat brain microvessels. Adult male F344 rats were sacrificed and blocks of the cerebral cortex and infratentorial areas were dissected. Microvessels were isolated using a filtration method, and total RNA was extracted. Two microarrays using four sample RNAs (microvessels from the cerebral cortex vs. microvessels from the infratentorial block) were included in the present study. Microarrays demonstrated that there were 16 PDE transcripts in the PDE superfamily, exhibiting quantifiable density in the microvessels.
2012-02-01 | E-GEOD-35285 | biostudies-arrayexpress
Project description:To date, miRNA expression studies on cerebral ischemia in both human and animal models have focused mainly on acute phase of ischemic stroke. In this study, we present the roles played by microRNAs in the spontaneous recovery phases in cerebral ischemia using rodent stroke models. In this study presented here, Middle Cerebral Artery Occlusion stroke model was established by using embolus and the brain samples of stroke model were harvested at 0hrs, 3hrs, 6hrs, 12hrs, 24hrs, 48hrs, 72hrs, 120hrs and 168hrs. RNAs were extracted from these samples and microRNA array and mRNA array were performed.
2013-12-09 | E-GEOD-46266 | biostudies-arrayexpress
Project description:Microglia are abundantly distributed throughout the central nervous system (CNS) to play critical roles in neural development and homeostasis, and act as immune sentinels to constantly monitor their surrounding neural environment. Given their high reactivity to brain insults, we hypothesised that the cerebral microenvironment altered by ischemic stroke would significantly impact microglial morphology and function in a spatially dependent manner. To investigate this, we examined regional changes in the expression of genes associated with microglial activation and neuroinflammation, microglial morphology using 3D image reconstruction and unbiased proteomics at 24 hours after transient middle cerebral artery occlusion (tMCAO). We found the microenvironment within the ischaemic infarct core has a distinct pro-inflammatory profile is very different to versus that of the sham-operated controls. , and more importantly this region of the brain displays dynamic and diverse inflammatory changes. Moreover, stroke induces region-specific changes to microglia morphology with those closer to the infarct displaying a more ameboid shape and less complex dendritic processes. Additionally, we identified 108 differentially expressed proteins in microglia that were isolated from the ipsilateral ischaemic hemisphere compared to those isolated from thethat of contralateral hemisphere. These differentially expressed proteins are predicted to influence signalling pathways that mediate TNF-α superfamily cytokine production, chemokine activities and leukocyte chemotaxis and migration. These findings support microglia as critical regulators of the inflammatory signalling after stroke. Mice Adult C57Bl/6J and Cx3cr1gfp/+ (both reporter strains are on C57Bl/6J background) male and female mice were obtained from the Monash Animal Research Platform and were housed at Monash Translational Health Precinct Animal Facility (MHTP-AF, Clayton, VIC, Australia) in specific pathogen-free (SPF) conditions with access to food and water ad libitum. Mice were housed in temperature-controlled rooms (22 °C) under a standard 12 h light-dark cycle. Prior to the start of experiments, mice were acclimatised for a minimum of 7 days before use. All procedures were approved by the Monash Medical Centre Animal Ethics Committee (MMCB/2018/002 and MMCB/2022/22, Monash Medical Centre, Clayton, Victoria, Australia). Middle cerebral artery occlusion (MCAO) surgery The mouse model of ischaemic stroke was performed as previously described (27), whereby infarct is induced in the right cerebral hemisphere. Briefly, mice were anaesthetised by intraperitoneal injection of ketamine (150 mg/kg) and xylazine (10 mg/kg). Once anaesthetised, an incision at the top of the head was made to expose the skull, and a laser Doppler holder (PeriFlux System 5000, Stroke model kit 407, Perimed, Järfälla-Stockholm, Sweden) was glued to the right side of the skull to monitor blood flow above the right hemisphere of the brain. The fur at the site of the neck incision was removed and the area was sterilised with 80 % ethanol. A 1–2-cm incision was made along the midline of the throat to expose the trachea. The right common carotid artery, external carotid artery, and internal carotid artery were dissected away from any connective tissue. A vessel clip was used on the right common carotid artery, and a slit was made in the external carotid artery. A silicone-coated monofilament with a diameter of 0.21–0.23 mm (Doccol Corporation) was immediately inserted into the external carotid artery and advanced into the internal carotid artery to occlude blood flow into the MCA. A successful occlusion was determined by >70% reduction in Doppler reading. The external carotid artery was tied off and the vessel clip removed. In this study, we utilised the reperfused model termed transient MCAO or tMCAO, whereby the monofilament was retracted to allow for reperfusion of blood flow into the MCA following 1 h of occlusion. After successful surgery, the neck incision was sutured closed, the doppler probe removed, and the head incision closed. As a control for surgical stress, sham operations were performed whereby similar surgical protocols were executed without the insertion of the monofilament. After surgery, all mice were allowed to recover overnight on a heat pad.
2025-12-22 | PXD055588 | Pride