RNA Sequencing of WT Chronic Stroke Infarcts vs. Contralateral Cortices
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ABSTRACT:
PROVIDER: PRJNA726051 | ENA |
REPOSITORIES: ENA
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Project description:We conducted bulk RNA sequencing on infarcts collected from young adult (3-month-old) mice at 7 weeks after the distal middle cerebral artery occlusion + hypoxia stroke model and compared them to contralateral cortices. As expected, differential expression (DE) analysis revealed marked differences between infarcts and contralateral cortices: 3,930 upregulated and 2,869 downregulated genes. The most significantly upregulated genes, including Lpl, Spp1, Cd36, Mmp2, and Mmp19, and the most highly enriched genes, including Cd5l, Mmp3, Mmp12, and Mmp13, indicate a pronounced disturbance in lipid homeostasis in infarcts at 7 weeks after stroke. In addition to alterations in lipid metabolic processes, the transcriptome also revealed a signature of chronic inflammation at 7 weeks after stroke. We then used IPA software to define upstream regulators and identify altered biological processes based on DE analysis. Differentially expressed genes were associated with the following upregulated biological processes: (i) atherosclerosis signaling, (ii) IL-1 signaling, (iii) inflammasome pathway, (iv) eicosanoid signaling, (v) B cell receptor (BCR) signaling, and (vi) phospholipases, along with others. IPA also identified lipid metabolic upstream regulators such as cholesterol, phospholipids, and LDL, as well as immunological upstream regulators such as MYD88, IL18, CD3, IL1B, TLR4, and TNF. These altered biological processes indicate that the stroke infarct transcriptome is characterized by chronic inflammation, dysregulated lipid metabolism, and impaired or absent neuronal function at 7 weeks after stroke.
2021-04-30 | GSE173544 | GEO
Project description:We report the identification of enhancer domains in sham and stroke mouse cerebral cortices by high-throughput profiling of H3K27Ac chromatin modification. A total of 35.4, 28.8 and 29.6 million reads were generated from chromatin immunoprecipitated DNA from sham, stroke and pooled input samples. This resulted in 55,571 peaks in sham and 56,110 peaks in stroke samples representing 50408 and 51,292 active regions, respectively. These active regions represent putative enhancer domains.
2020-11-12 | GSE135480 | GEO
Project description:We have used microarrays to investigate the changes in gene expression at various times after stroke. Our findings reported that gene expression screening can detect known and unknown transcriptional features of stroke. Brain samples were obtained from 9 patients who died from stroke, with the approval of the local Ethics Committee. The patients were aged between 51 and 86 years and had survived between 2-37 days following stroke. Tissue samples were taken from infarct and peri-infarcted zones while controls were obtained from the contralateral hemisphere. We established mRNA expression profiles of the damaged brain tissues between 2 to 6 days, 9 to 20 days, and 26 to 37 days after stroke. RNA from three stroke patients was pooled for each patient survival group.
2010-06-25 | E-GEOD-9391 | biostudies-arrayexpress
Project description:Prior to assessing the impact of repeated HPβCD administration on the peri-infarct region of the brain, we first compared the transcriptome of the peri-infarct region to the equivalent region of the contralateral hemisphere in aged (18-month-old) mice at 7 weeks after distal middle cerebral artery occlusion + hypoxia (DH) stroke. The peri-infarct region was characterized by 3,910 differentially expressed genes. Of these, 2,123 were upregulated, many of which were also upregulated in infarcts at 7 weeks after stroke. For instance, the infarct and peri-infarct regions were both defined by the upregulation of degradative enzymes, TLRs, and scavenger receptors. In addition, the upregulation of Lpl, Lrp2, Ch25h, Apoe, Trem2, and Abca1 signified a divergence from lipid homeostasis. These alterations in innate immunity coincided with corresponding perturbations in adaptive immunity. The upregulation of Cd3d, Cd3e, Cd3g, Blnk, Sdc1 and Jchain suggests that chronic inflammation persists in peri-infarct regions for at least 7 weeks after stroke. Conversely, the DE analysis revealed that 1,787 genes were downregulated in peri-infarct regions compared to equivalent regions of the contralateral hemisphere. These genes were primarily involved in mitochondrial respiration and neuronal function. Together, these results demonstrate that the transcriptome of the peri-infarct region is characterized by the upregulation of genes involved in inflammation and lipid metabolism and the downregulation of genes involved in mitochondrial respiration and neuronal function. To evaluate the impact of HPβCD treatment on the transcriptome of the peri-infarct region, we also performed bulk RNA-Seq on brain tissue collected 7 weeks after DH stroke. For this analysis, we compared the peri-infarct regions of vehicle- and HPβCD-treated aged mice. The peri-infarct region of HPβCD-treated mice was characterized by 5,385 differentially expressed genes. The DE analysis revealed that peri-infarct regions of HPβCD-treated mice were characterized by the downregulation of multiple degradative enzymes, chemokine receptors, and scavenger receptors. In addition, the transcriptomic analysis demonstrated a restoration of lipid homeostasis in peri-infarct regions of HPβCD-treated mice compared to vehicle-injected mice, as evidenced by the downregulation of Lipa, Apoe, Lamp1, Npc1, and Npc2 and upregulation of Nceh1 and Ldlr. Reductions in innate and adaptive immune responses characterized peri-infarct regions of HPβCD-treated mice; these alterations are consistent with the attenuated chronic inflammation that characterized infarcts of the HPβCD-treated aged mice. These results demonstrate that HPβCD treatment after stroke attenuates chronic inflammation and promotes lipid metabolism in peri-infarct regions of aged mice. Additionally, the DE analysis revealed an upregulation of genes involved in myelin sheath structural integrity, such as Ina, Omg, and Nefl, and synaptic plasticity and neuroplasticity, such as Syn1, Bdnf, Nrg1, Negr1, and Nsg1. These results suggest that HPβCD treatment improves the structure and function of neurons in peri-infarct regions of aged mice after stroke.
2021-05-03 | GSE173714 | GEO
Project description:Genome-wide identification of enhancer domains in the healthy and post-stroke mouse cortices
| PRJNA559075 | ENA
Project description:Neonatal hypoxic-ischemic (HI) encephalopathy can lead to severe brain damage and is a common cause of neurological handicaps in adulthood. To elucidate the molecular events occurring in cerebral cortices of mature rats (8 weeks old) after neonatal HI brain insult, we performed comprehensive gene expression and gene network analyses using a DNA microarray system (Agilent 4x44K). A rat model of neonatal HI encephalopathy (Rice model) was obtained by unilateral ligation of the common carotid artery of 7-day-old rats with hypoxia (exposure to 8% oxygen). Due to the HI insult-related breakdown of the ipsilateral hemisphere in the brain, RNAs were prepared from the contralateral cerebral cortices of 8-week-old rats and analyzed by DNA microarray. Biofunctional analysis of differentially regulated genes revealed that many upregulated genes were related to cell death signaling, such as the arachidonic acid cascade. In contrast, many downregulated genes were related to gene expression, reflecting progressive damage by the HI insult, even within the contralateral cerebral hemisphere.
2012-06-28 | GSE37777 | GEO
Project description:<p>The goal of this study was to evaluate changes in metabolic homeostasis during the first 12 weeks of recovery in a distal middle cerebral artery occlusion mouse model of stroke. To achieve this goal, we compared the brain metabolomes of ipsilateral and contralateral hemispheres from aged male mice up to 12 weeks after stroke to that of age-matched naïve and sham operated mice. There were 707 biochemicals detected in each sample by liquid chromatography-mass spectroscopy (LC-MS). Mitochondrial fatty acid β-oxidation, indicated by acyl carnitine levels, was increased in stroked tissue at 1 day and 4 weeks following stroke. Glucose and several glycolytic intermediates were elevated in the ipsilateral hemisphere for 12 weeks compared to the aged naïve controls, but pyruvate was decreased. Additionally, itaconate, a glycolysis inhibitor associated with activation of anti-inflammatory mechanisms in myeloid cells, was higher in the same comparisons. These changes correlated with reduced levels of glutamate, dopamine, and adenosine in the ipsilateral hemisphere after stroke. These results indicate that chronic metabolic differences exist between stroked and control tissue, including alterations in fatty acid metabolism and glycolysis for at least 12 weeks after stroke.</p>
2022-10-06 | MTBLS5543 | MetaboLights
Project description:RNA-sequencing was conducted to profile the transcriptome of the eRNA_06347 knockdown post-stroke mouse cortices ( knockdown achieved by intracerebroventricular injection of oligos against eRNA_06347). RNA was isolated from sham, Negative control oligo injected post-stroke cortices and eRNA_06347 knockown post-stroke cortices (three independent biological replicates per group),converted into cDNA libraries, and used for Illumina deep sequencing.The sequencing reads were aligned to the mouse reference genome GRCm38 using HISAT2. Stringtie was used to assemble the aligned sequences into transcript isoforms using mouse transcript annotations from Ensembl 81 as a guide, then merged to reconstruct a comprehensive transcriptome using perl scripts and gffcompare. After the final transcriptome was generated, StringTie and Ballgown were used to estimate the expression levels of all the transcripts. StringTie was used to evaluate expression levels for mRNAs by calculating the FPKMs. The differentially expressed mRNAs were identified as log2 fold change >1 or log2 fold change <-1 and with statistical significance p<0.05 using Ballgown.Doing so, We found that 106 genes were significantly upregulated and 49 genes were significantly downregulated in the eRNA_06347 knockdown group as compared to the negative control.
2020-11-12 | GSE136405 | 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:The blood-brain barier (BBB) function is impaired in several neurological diseases such as stroke. To better study the BBB dysfunction in stroke and to identify novel therapeutic targets, a detailed analysis of the neurovascular unit (NVU) cells that together regulate the BBB function is needed. To this end, we isolated the NVU cells EC, PC, AC, MG post stroke in mice using our newly developed SGD (Spitzer, Guérit, Devraj) method from the same starting material followed by RNA sequencing. Cells were isolated from both healthy appearing contralateral hemisphere and ipsilateral stroke hemisphere post tMCAO (1h occlusion, 23h repurfusion) using the SGD method. Each sample comprised 6 biological replicates with each replicate pooled from 3-4 male C57BL6 adult mouse brains either from contralateral or ipsilateral hemisphere post stroke. Only mice with neurological scores (mNSS) of atleast 8 were included for the NVU cell isolation. Our data showed regulation of several genes post stroke in each of the cell types analyzed with novel candidates that were co-regulated in the NVU cell types. As the blood-brain barrier (BBB) is co-regulated by several NVU cell types, we propose targeting the candidates co-regulated in multiple NVU cell-ytpes for novel and effective therapeutic options in stroke.
2022-07-20 | GSE163752 | GEO