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:Model organism or animal sample
Project description:In this study, cerebral cortical astrocytes and neurons of rats were co-cultured, the astrocytes of the co-cultured cell model pretreated by ischemic preconditioning (45 min of OGD) were subjected to lncRNA high-throughput sequencing (RNA-seq).
Project description:To reveal the molecular signatures of XingNaoKaiQiao acupuncture on the Cerebral cortex of rats with cerebral ischemia/reperfusion injury, we performed bulk RNA sequencing.
Project description:Ischemic tolerance can be induced by numerous preconditioning stimuli, including various Toll-like receptor (TLR) ligands. We have shown previously that systemic administration of the TLR4 ligand, lipopolysaccharide (LPS) or the TLR9 ligand, unmethylated CpG ODNs prior to transient brain ischemia in mice confers substantial protection against ischemic damage. To elucidate the molecular mechanisms of preconditioning, we compared brain and blood genomic profiles in response to preconditioning with these TLR ligands and to preconditioning via exposure to brief ischemia. The experiment is a comparison of multiple treatment groups with sampling at multiple time points. The objective is to identify differentially regulated genes associated with preconditioning. Time points are examined both following preconditioning alone and following subsequent ischemic challenge (middle cerebral artery occlusion (MCAO)). Brain ipsilateral cortex tissue and blood were collected and processed from each animal. 6 experimental conditions: (n=3-4 mice/condition) LPS treated (i.p. 0.2mg/kg) + ischemic challenge (45min MCAO) CpG treated (i.p. 0.8mg/kg) + ischemic challenge (45min MCAO) Saline treated (i.p.) + ischemic challenge (45min MCAO) brief ischemia (12 min MCAO) + ischemic challenge (45min MCAO) Sham of brief ischemia (12 min) + ischemic challenge (45min MCAO) Non-treated + ischemic challenge (45min MCAO) Time points: Pre-ischemic challenge 3hr 24hr 72hr Post-ischemic challenge 3hr 24hr Unhandled (6 mice)-BASELINE
Project description:<p>Neonatal hypoxic-ischemic encephalopathy (HIE) refers to nervous system damage caused by perinatal hypoxia, which is the major cause of long-term neuro-developmental disorders in surviving infants. However, the mechanisms still require further investigation. In this study, we found that the butanoate metabolism pathway exhibited significantly decreased and short chain fatty acid (SCFAs)-producing bacteria, especially butyrate-producing bacteria, were significantly decreased in fecal of neonatal hypoxic-ischemic brain damage (HIBD) rats. Surprisingly, Sodium butyrate (SB) treatment could ameliorate pathological damage both in the cerebral cortex and hippocampus and facilitate recovery of SCFAs-producing bacteria related to metabolic pathways in neonatal HIBD rats. Moreover, we found that in samples from SB treatment neonatal HIBD rats cortex with high levels of butyrate acid along with aberrant key crotonyl-CoA-producing enzymes ACADS levels was observed compared HIBD rats. We also demonstrated that a decrease in histone 3-lysine 9-crotonylation (H3K9cr) downregulated expression of the HIE-related neurotrophic genes Bdnf, Gdnf, Cdnf, and Manf in HIBD rats. Furthermore, SB restored H3K9cr binding to HIE-related neurotrophic genes. Collectively, our results indicate that SB contributes to ameliorate pathological of HIBD by altering gut microbiota and brain SCFAs levels subsequently affecting histone crotonylation-mediated neurotrophic-related genes expression. This may be a novel microbiological approach for preventing and treating HIE.</p><p><br></p><p><strong>Brain tissue metabolomics</strong> is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS4894' rel='noopener noreferrer' target='_blank'><strong>MTBLS4894</strong></a>.</p><p><strong>Feces metabolomics</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS4893' rel='noopener noreferrer' target='_blank'><strong>MTBLS4893</strong></a>.</p>
Project description:Ischemic stroke triggers severe focal hypoperfusion accompanied with deprivation of oxygen and glucose to the cerebral tissue, together with loss of ATP, depolorization of neurons, elevated extracellular potassium concentration, and subsequently leads to excitotoxicity as well as increased oxidative stress promoting microvascular injury, blood-brain-barrier deregulation, post-ischemic inflammation and eventually the consequential neurological deficit. Although reperfusion of ischemic brain tissue is critical for restoring normal function, it can paradoxically result in secondary damage, called ischemia/reperfusion (I/R) injury. Microarray analysis was performed on the right striatum and cortex (corresponded to infarct area) of post-I/R injured brain tissues of wild-type (WT-MCAO) using Illumina mouse Ref8 V2 genechips. Suture-induced middle cerebral artery occlusion was induced for 2h followed by reperfusion, with tissue extraction taking place 2h, 8h and 24h post-reperfusion (n=4 respectively). Sham controls were included in this study too (n=4 respectively).
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.
Project description:Neuroprotection has not been successfully translated from animals to humans, and controversies persist about the suitability of animal models for the evaluation of putative stroke therapies. Of these, many appear to be less effective in mice as compared with rats. We hypothesized that this may be due to fundamental interspecies differences in stroke response. Whole-genome microarrays were used to examine differential gene regulation in the ischemic penumbra of mice and rats 2hrs and 6hrs after permanent middle cerebral artery occlusion (pMCAO). The differentially expressed genes in the ischemic penumbra at each time point were compared between the two species.
Project description:To date, miRNA and mRNA 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 harvestd 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.