Profiling brain cortex from tMCAO rat stroke model
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: I-Ming Wang
PROVIDER: E-GEOD-38037 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Systems analysis of eleven rodent disease models reveals an inflammatome signature and key drivers.
Wang I-Ming IM Zhang Bin B Yang Xia X Zhu Jun J Stepaniants Serguei S Zhang Chunsheng C Meng Qingying Q Peters Mette M He Yudong Y Ni Chester C Slipetz Deborah D Crackower Michael A MA Houshyar Hani H Tan Christopher M CM Asante-Appiah Ernest E O'Neill Gary G Luo Mingjuan Jane MJ Thieringer Rolf R Yuan Jeffrey J Chiu Chi-Sung CS Lum Pek Yee PY Lamb John J Boie Yves Y Wilkinson Hilary A HA Schadt Eric E EE Dai Hongyue H Roberts Christopher C
Molecular systems biology 20120717
Common inflammatome gene signatures as well as disease-specific signatures were identified by analyzing 12 expression profiling data sets derived from 9 different tissues isolated from 11 rodent inflammatory disease models. The inflammatome signature significantly overlaps with known drug targets and co-expressed gene modules linked to metabolic disorders and cancer. A large proportion of genes in this signature are tightly connected in tissue-specific Bayesian networks (BNs) built from multiple ...[more]
Similar Datasets
Project description:This program addresses the gene signature associated with brain (cortex) in the tMCAO rat model for stroke.
2013-03-22 | GSE38037 | GEO
Project description:Samples from three groups, SHAM operated group and two STROKE operated groups treated two days post operation with AAV1-eGFP control and AAV1-MANF treatment were sequenced and analysed for differential gene expression
2020-04-12 | E-MTAB-8339 | biostudies-arrayexpress
Project description:Genes upregulated in stroke infiltrating stem cells were compared against the parent non-infiltrated mouse stem cell line derived from immortomouseTM. Abstract Background and Purpose- Although the therapeutic potential of bone marrow-derived stem cells (SC) has been addressed in different experimental models of ischemic stroke, it is still unclear how SC induce neuroprotection following stroke. In this study, we describe a novel method for recovering SC infiltrating post-stroke brain tissue allowing the determination of genes which become persistently activated / or depressed (compared to their naïve counterparts) during SC-mediated neuroprotection. Methods- Ischemic stroke was induced in C57BL/6 mice by middle cerebral artery occlusion for 1 h, followed by reperfusion. SC were isolated from H-2Kb-tsA58 (immortomouseTM) mice, and were administered (i.v.) 24 h after reperfusion. At the onset of therapeutic improvement (14 days after ischemia), infarcted brain tissue was isolated and infarct-infiltratng SC cultured at 33°C. Microarray analysis and RT-PCR were performed to compare persistent differential gene expression between naïve and infiltrating SC populations. Results- Z-scoring revealed dramatic changes in extracellular genes of analyzed cells. Pair-wise analysis detected 80 extracellular factor genes that were up-regulated ( 2 fold, P<0.05, Benjamini-Hochberg correction) between naïve and infiltrated SC. Although several conventional neuroregenerative, nerve guidance and angiogenic factors (bFGF, bone morphogenetic protein, angiopoietins, neural growth factors were among the expressed genes detected we identified Cytokine receptor-like factor 1 (Crlf1), Fgf7, family with sequence similarity 19, member A5 (Fam19a5), Glypican 1 (Gpc1), Dickkopf homolog 2 (Dkk2), Endothelial cell-specific molecule 1, Osteopontin (OPN)35, Tissue factor pathway inhibitor 2, Masp3 mRNA for MBL-associated serine protease-3, Glial cell line derived neurotrophic factor (Gdnf), Bone morphogenetic protein 2 (Bmp2), Olfactomedin 1, Sushi-repeat-containing protein, X-linked 2 (Srpx2). Conclusions- SC infiltrating the post-i schemic brain assume a persistently altered pattern of expressed extracellular genes compared to naïve SC that contributes to neuroprotection, regeneration and angiogenesis in infarcts. Keywords: Gene activation / suppression study Comparison of persistent stem cell gene expression induced by stroke-infarct infiltration
2010-12-31 | E-GEOD-21393 | biostudies-arrayexpress
Project description:Selective isolation of total RNA and then whole genome expression analysis of sprouting neurons in peri-infarct cortex of the adult rat after stroke, compared to adjacent neurons that have not sprouted a new connection, in young adult (2 months) and aged (2 years) animals. Two different fluorescent conjugates of the tracer cholera toxin B (CTb), CTb-Alexa 488 and CTb-Alexa 647 (Molecular Probes), were sequentially injected into peri-infarct cortex at the sites of post-stroke axonal sprouting using a picospritzer pressure injection system. After survival periods of 7 days and 21 days (separate cohorts of animals), CTb-647 was injected exactly within CTb-488 injection site. Seven days after the second tracer injection, laser capture microdissection (LCM) was used to capture ~300 neurons for each cell type. Total RNA was isolated from captured cells and subjected to two rounds of T7 amplification.
2010-11-15 | E-GEOD-24440 | biostudies-arrayexpress
Project description:Selective isolation of total RNA and then whole genome expression analysis of sprouting neurons in peri-infarct cortex of the adult rat after stroke, compared to adjacent neurons that have not sprouted a new connection, in young adult (2 months) and aged (2 years) animals. Two different fluorescent conjugates of the tracer cholera toxin B (CTb), CTb-Alexa 488 and CTb-Alexa 647 (Molecular Probes), were sequentially injected into peri-infarct cortex at the sites of post-stroke axonal sprouting using a picospritzer pressure injection system. After survival periods of 7 days and 21 days (separate cohorts of animals), CTb-647 was injected exactly within CTb-488 injection site. Seven days after the second tracer injection, laser capture microdissection (LCM) was used to capture ~300 neurons for each cell type. Total RNA was isolated from captured cells and subjected to two rounds of T7 amplification.
2010-11-15 | E-GEOD-24441 | biostudies-arrayexpress
Project description:Stroke remains a major leading cause of death and disability worldwide. Despite continuous advances, the identification of key molecular signatures of ischemic stroke within the hyper-acute phase of the disease is still of primary interest for a real translational research on stroke diagnosis, prognosis and treatment. High-throughput - omics technologies are enabling large-scale studies on stroke pathology at different molecular levels. Data integration resulting from these -omics approaches is becoming crucial to unravel the interactions among all different molecular elements and highly contribute to interpret all findings in a complex biological context. Here, we have used advanced data integration methods for multi-level joint analysis of transcriptomics and proteomics datasets depicted from the mouse brain 2h after cerebral ischemia. By modeling network-like correlation structures, we identified a set of differentially expressed genes and proteins by ischemia with a relevant association in stroke pathology. The ischemia-induced deregulation of 10 of these inter-correlated elements was successfully verified in a new cohort of ischemic mice, and changes in their expression pattern were also evaluated at a later time-point after cerebral ischemia. Of those, CLDN20, GADD45G, RGS2, BAG5 and CTNND2 were highlighted and evaluated as potential blood biomarkers of cerebral ischemia in blood samples from ischemic and sham-control mice and from ischemic strokes and other patients presenting stroke-mimicking conditions. Our findings indicated that CTNND2 and GADD45G levels in blood within the first hours after ischemic stroke might be potentially useful to discriminate ischemic strokes from mimics and to predict patients’ poor outcome after stroke, respectively. In summary, we have here used for the first time an integrative approach to elucidate by means of biostatistical tools key elements of the initial stages of the stroke pathophysiology, highlighting new outstanding proteins that might be further considered as blood biomarkers of ischemic stroke.
2020-09-02 | PXD016538 | Pride
Project description:1. Rationale: Stroke is still a major cause of death and disability worldwide. A better comprehension of stroke pathophysiology is fundamental to reduce its dramatic outcome. The use of high-throughput unbiased omics approaches, such as proteomics and transcriptomics, might aid to deepen the knowledge of stroke at the molecular level. Moreover, the integration of omics data is needed to depict the existing interaction between different molecular units and interpret the results in a global biological context. 2. Objective: Our aim was to identify and verify protein and gene expression changes that occur in the human brain after ischemia through an integrative approach to join and combine the information of both omics analyses. The translational potential of our results was explored in a pilot study with blood samples from ischemic stroke patients. 3. Methods and results: Proteomics and transcriptomics discovery studies were performed in human brain samples from deceased stroke patients, unveiling 128 proteins and 2716 genes significantly dysregulated after cerebral ischemia. Afterwards, integrative bioinformatics analyses joining both datasets exposed several canonical pathways altered in the ischemic area, such as neurotransmitters release or matrisome regulation, highlighting the most influential molecules in these pathways. To conduct the verification phase, 28 genes and 9 proteins were selected to be validated in independent human brain samples by means of orthogonal techniques. Our results were confirmed for NCDN, RAB3C, ST4A1, DNM1L, A1AG1, A1AT, JAM3, VTDB, ANXA1, ANXA2 and IL8. Finally, the blood circulating levels of the validated protein candidates were explored in ischemic stroke patients over the acute phase of the disease. Protein fluctuations along the first week after onset were detected for A1AG1 and A1AT. 4. Conclusion: The results presented here expand the knowledge of stroke pathology, revealing new key molecules that can be further explored as biomarkers and/or therapeutic targets of ischemic stroke.
2022-12-21 | PXD022850 | Pride
Project description:TMT-coupled proteomic analysis was conducted on mouse brain cortex tissue from five time-points up to four weeks post-stroke in the DH-MCAO mouse model. Nearly-half of the detected proteome was altered following stroke, with <10% of changes at relatively large scales. Clustering on the changed proteome defined four distinct expression patterns characterized by temporal and quantitative changes in innate and adaptive immune response pathways, and cytoskeletal and neuronal remodeling. Further analysis on a subset of top-hits, which temporally responded to stroke with relatively large and sustained changes, revealed that they were highly correlated to different cortical cytokines, and thereby potential pharmacodynamic biomarker candidates for inflammation-targeting therapies. Closer examination of the top enriched neurophysiologic pathways identified 57 proteins potentially associated with post-stroke recovery. Altogether, our study generated a rich dataset with candidate proteins worthy of further validation as biomarkers and/or therapeutic targets for stroke.
2021-06-10 | PXD025077 | Pride
Project description:The goal was to identify lesion- and AAV7-MANF-induced gene expression changes in the peri-infarct cortex of rats that had undergone a 60 minute distal middle cerebral artery occlusion 4 days earlier. Intracerebral infusion of AAV7-GFP or AAV7-hMANF was done 2 days later (i.e. 2 days before collecting the samples). Sham operated control rats underwent a craniotomy surgery, but no artery ligation or intracerebral infusion.
2018-05-04 | E-MTAB-6709 | biostudies-arrayexpress
Project description:While multiple studies have reported the accelerated evolution of brain gene expression in the human lineage, the mechanisms underlying such change remain poorly understood. Here we address this issue from a developmental perspective, by analyzing mRNA and microRNA (miRNA) expression in two brain regions within macaques, chimpanzees and humans throughout their lifespan. We find that developmental profiles of trans-regulators, such as miRNA, as well as their target genes, show the fastest rates of human-specific evolutionary change. Changes in expression of a few key regulators may be a major driving force behind human brain evolution. Human, chimpanzee and rhesus macaque post-mortem brain samples from the prefrontal cortex and cerebellar cortex were collected. The age ranges of the individuals in all three species covered the respective species' postnatal maturation period from infancy to old adulthood. RNA extracted from the dissected tissue was hybridized to B72.
2011-12-09 | E-GEOD-29356 | biostudies-arrayexpress