Transcriptomic profiling of rat brain tissue 21 days after middle cerebral artery occlusion
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE345807 | GEO | 2026/09/11
REPOSITORIES: GEO
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Project description:Ischemic stroke is a leading cause of death and disability worldwide. Recanalization therapies for acute ischemic stroke, which include mechanical thrombectomy and rt-PA delivery, are limited as while the operations are successful, many patients experience poor clinical outcomes, termed futile recanalization. Using the murine middle cerebral occlusion (MCAO) model that mimics a large vessel occlusion with recanalization, we performed a comprehensive microarray analysis of blood samples post-MCAO and recanalization in male, female, young adult, and aged mice (N=44). Downstream bioinformatics analysis was then performed in RStudio. We discovered 11 hub genes that are potential genomic markers of early recanalization changes in mice. Vcan, a novel marker, is highly conserved and elevated in mice, rats, and clinical patients. Leukocyte and neutrophil functional activities have significant enrichment in both mice and humans. We identified a range of miRNAs that potentially regulated recanalization responses and NFE4 and MTF1 as the primary transcription factors. MCAO was performed MCAO mice were euthanized immediately 60 minutes after surgery. In the MCAO+Recan group, the suture was taken out 60 minutes after the onset of occlusion and mice were allowed to recover for an additional 3 hours before euthanasia. Sham mice were subjected to only anaesthesia and the manipulation of surrounding tissues and arteries.
2025-10-31 | GSE278554 | GEO
Project description:Astrogliosis is a hallmark of the response to brain ischemia, comprised of changes in gene expression and morphology. Hsp72 protects from cerebral ischemia, and although several mechanisms of protection have been investigated, effects on astrocyte activation are unknown. To identify potential mechanisms of protection, gene expression was assessed in mice subjected to middle cerebral artery (MCAO) or sham surgery, of either wildtype (WT) or Hsp72-overexpressing (Hsp72Tg) mice. After stroke, both genotypes exhibited genes related to cell death, stress response, and immune response. Furthermore, genes indicative of astrocyte activation, including cytoskeletal proteins and cytokines, were upregulated. To measure astrocyte activation after stroke, detailed histological and morphological analyses were performed in the cortical penumbra after stroke using unbiased stereology. Consistent with other reports, we observed a marked and persistent increase in glial fibrillary acidic protein (GFAP ) as soon as 3 hours after MCAO. In contrast, vimentin immunoreactivity appeared 12-24 hours after stroke, peaked at 72 hours, and returned to baseline after 30 days. Surprisingly, no change in overall astrocyte number was observed based on glutamine synthetase (GS) immunoreactivity. To determine if Hsp72Tg mice exhibited altered astrocyte activation compared to WT controls, morphological evaluation by fractal analysis was used. Overexpression of Hsp72 reduced astrocyte cell area, arbor area, and to a lesser extent fractal dimension, 72 hours following stroke. In conclusion, in vivo overexpression of Hsp72 alters gene expression following stroke, including genes involved in astrocyte activation, and decreases astrocyte activation acutely following MCAO. Thus, modulation of astrogliosis may be a neuroprotective mechanism exerted by Hsp72 after ischemia. A total of 10 samples were analyzed, with 5 of each genotype, wildtype (WT) and Hsp72-overexpressing (Hsp72Tg) mice. Of the 5 in each group, 3 received middle cerebral artery occlusion (MCAO) and 2 received a sham surgery. The sham samples serve as the controls for the MCAO samples in each genotype. All samples were taken from the ischemic or control hemisphere 24 hours after surgery.
2013-01-11 | E-GEOD-28731 | biostudies-arrayexpress
Project description:In the search for stroke biomarkers, miRNAs are gaining attention. To investigate novel miRNAs that work as stroke biomarkers, we used Middle Cerebral Artery Occlusion model of rats. By using microarray analysis and comparing with Sham operated rats, we extracted the miRNAs whose expressions are alterated by stroke.
2018-02-15 | GSE97532 | GEO
Project description:To analyze the gene expression alteration after stroke, we used Middle Cerebral Artery Occlusion model of rats. By comparing with Sham operated rats, we extracted the mRNAs whose expressions are alterated by stroke. Using microarray analysis, we aimed to grasp the overall expression alteration of mRNA in blood after stroke.
2018-02-14 | GSE97533 | GEO
Project description:To analyze the gene expression alteration after stroke, we used Middle Cerebral Artery Occlusion model of rats. By comparing with Sham operated rats, we extracted the mRNAs whose expressions are alterated by stroke. Using microarray analysis, we aimed to grasp the overall expression alteration of mRNA in brain after stroke.
2018-07-12 | GSE97537 | GEO
Project description:IL-6 Ko and wildtype control mice were subjected to 30 min left filamentous middle cerebral artery occlusion (MCAo)/reperfusion or sham operation. Animals were killed at 2 and at 10 days after MCAo or sham operation, respectively. The left (i.e. ischemic) hemisphere was used for further gene expression analysis.
2011-01-01 | E-MEXP-2547 | 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
Project description:Reactive astrogliosis is characterized by a profound change in astrocyte phenotype in response to all CNS injuries and diseases. To better understand the reactive astrocyte state, we used Affymetrix GeneChip arrays to profile gene expression in populations of reactive astrocytes isolated at various time points after induction using two different mouse injury models, ischemic stroke and neuroinflammation. Young adult male mice underwent middle cerebral artery occlusion (MCAO) to produce ischemic stroke or control sham surgery. Young adult mice were injected intraperitoneally with 5 mg/kg lipopolysaccharide (LPS) to produce neuroinflammation or saline for control. Astrocytes were acutely purified from control and injured brains at 1 day after injury for LPS/saline injection and 1, 3 days and 7 days after MCAO/sham surgeries.
2012-05-01 | E-GEOD-35338 | biostudies-arrayexpress
Project description:Stroke is a leading cause of mortality and long-term disability and ischemic stroke accounts for 87% of all strokes. Though timely recanalization of the occluded vessel is essential in the treatment of ischemic stroke, it is well known to cause ischemia-reperfusion (I/R) injury which result in neuronal cell death, brain tissue loss and severe neurological deficits. In this work, we employed a global proteomic approach to examine the changes of cerebral cortex proteins in rats undergoing acute and long-term I/R injury. In vivo middle cerebral artery occlusion (MCAO) model of focal cerebral I/R injury in rats was established. The animals were divided into three model groups with 2 h-MCAO followed with different reperfusion time, 1 day, 7 days and 14 days, respectively. For each model group a sham group was correspondingly set. Each group included four animals. For proteomic analysis, cerebral cortex proteins were extracted and analyzed by SDS-PAGE, whole-lane slicing, in-gel digestion and label-free quantitative LC-MS/MS. A total of 5621 proteins were identified and their quantities between the surgery and corresponding sham groups and across the three reperfusion time points were compared for mechanism investigation. This dataset includes all the raw files of the 840 LC-MS runs (6 groups x 4 animals x 35 gel squares/sample), as well as their identification and quantitation results at the levels of peptide fragments, peptides and proteins, respectively.
2019-07-03 | PXD012151 | Pride
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