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 net-like correlation structures, we identified a set of differentially expressed genes and proteins 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 as potential candidates as blood biomarkers of cerebral ischemia and hence they were evaluated in blood samples from ischemic and sham-control mice and in ischemic strokes and 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 that enabled us to elucidate by means of biostatistical tools key elements of the initial stages of the stroke pathophysiology and highlight new outstanding proteins that might be further considered as blood biomarkers of ischemic stroke.
Project description:4 Adult male Sprague-Dawley rats (275-350 g) were anesthetized and subjected to hepatectomy sham surgery (abdominal cavity was opened, liver was handled, but no tissue resection was made). 1 hour after the surgery rats were killed and liver samples were harvested. This study was conducted to analyzes the effects of surgical stress on gene expression levels in rat liver. It provides additional data to 1-6 h partial hepatectomy study (Series GSE7415). Keywords: 1h hepatectomy sham surgery
Project description:Middle cerebral artery occlusion (MCAo) in rat represent the ischemic stroke in human. Rodents subjected to MCAo and treated with venom phospholipase A2 showed reduction in infarct volume after 24hours of stroke. We studied the global gene expression of the reduction in infarct volume using Affymetrix Gene Chips. We analysed all the genes that were up or down regulated in the study. Total RNA isolated from sham, MCAo and MCAo+nPLA rat brains, was pooled to minimize inter-individual variation and hybridized to each array of the RAE-230A or U34A GeneChipTM according to protocols described in the GeneChipTM expression analysis package (Affymetrix, CA).
Project description:Adult mouse cortical tissues after MCAO or sham surgery were analyzed by ribosomal profiling to assess differences in ribosome associated mRNA fragments in I/R injury model of stroke.
Project description:Adult mouse cortical tissues after MCAO or sham surgery were analyzed by Argonaute HITS-CLIP to assess differences in transcriptome-wide AGO binding patterns in I/R injury model of stroke.
Project description:Adult mouse cortical tissues after MCAO or sham surgery were analyzed by RNAseq at various time points after reperfusion to assess differences in mRNA abundance in I/R injury model of stroke.
Project description:Adult mouse cortical tissues after MCAO or sham surgery were analyzed by small RNAseq at various time points after reperfusion to assess differences in miRNA abundance in I/R injury model of stroke.
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.