Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effect of Dexmedetomidine on ncRNA and mRNA Profiles of Cerebral Ischemia-Reperfusion Injury in Transient Middle Cerebral Artery Occlusion Rats Model

ABSTRACT: Ischemic stroke poses a significant global health burden, with rapid revascularization treatments being crucial but often insufficient to mitigate ischemia-reperfusion (I/R) injury. Dexmedetomidine (DEX) has shown promise in reducing cerebral I/R injury, but its potential molecular mechanism, particularly its interaction with non-coding RNAs (ncRNAs), remains unclear. This study investigates DEX's therapeutic effect and potential molecular mechanisms in reducing cerebral I/R injury. A transient middle cerebral artery obstruction (tMACO) model was established to simulate cerebral I/R injury in adult rats. DEX was administered pre-ischemia and post-reperfusion. RNA sequencing and bioinformatic analyses were performed on the ischemic cerebral cortex to identify differentially expressed non-coding RNAs (ncRNAs) and mRNAs. The sequencing results showed 6494 differentially expressed (DE) mRNA and 2698 DE circRNA between the sham (S) and tMCAO (I/R) groups. Additionally, 1809 DE lncRNA, 763 DE mRNA, and 2795 DE circRNA were identified between the I/R group and tMCAO+DEX (I/R+DEX) groups. Gene ontology (GO) analysis indicated significant enrichment in multicellular biogenesis, plasma membrane components, and protein binding. KEGG analysis further highlighted the potential mechanism of DEX action in reducing cerebral I/R injury, with hub genes involved in inflammatory pathways. This study demonstrates DEX's efficacy in reducing cerebral I/R injury and offers insights into its brain-protective effects, especially in ischemic stroke. Further research is warranted to fully understand DEX's neuroprotective mechanisms and its clinical applications.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE268634 | GEO | 2024/07/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Effect of Celastrol on LncRNAs and mRNAs Profiles of Cerebral Ischemia-Reperfusion Injury in Transient Middle Cerebral Artery Occlusion Mice Model

Project description:Celastrol plays a significant role in cerebral ischemia-reperfusion injury. Although previous studies have confirmed that celastrol post-treatment has a protective effect on ischemic stroke, the therapeutic effect of celastrol on ischemic stroke and the underlying molecular mechanism remain unclear. In the present study, focal transient cerebral ischemia was induced by transient middle cerebral artery occlusion (tMCAO) in mice and celastrol was administered immediately after reperfusion. We performed lncRNA and mRNA analysis in the ischemic hemisphere of adult mice with celastrol post-treatment through RNA-Sequencing (RNA-Seq). A total of 50 differentially expressed lncRNAs (DE lncRNAs) and 696 differentially expressed mRNAs (DE mRNAs) were identified between the sham and tMCAO group, and a total of 544 DE lncRNAs and 324 DE mRNAs were identified between the tMCAO and tMCAO+celastrol group. Bioinformatic analysis was done on the identified deregulated genes through gene ontology (GO) analysis, KEGG pathway analysis and network analysis. Pathway analysis indicated that inflammation-related signaling pathways played vital roles in the treatment of ischemic stroke by celastrol. Our study suggests celastrol treatment can effectively reduce cerebral ischemia-reperfusion injury. The bioinformatics analysis of lnRNAs and mRNAs profiles in the ischemic hemisphere of adult mice provides a new perspective in the neuroprotective effects of celastrol, particularly with regards to ischemic stroke.

2022-05-13 | GSE202659 | GEO

Single-cell analyses reveal the dynamic functions of Itgb2+ microglia subclusters at different stages of cerebral ischemia-reperfusion injury in transient middle cerebral occlusion mice model

Project description:The underlying pathophysiological mechanisms of cerebral ischemia-reperfusion injury (CIRI) is intricate, and current studies suggest that neuron, astrocyte, microglia, endothelial cell, and pericyte all have different phenotypic changes of specific cell types after ischemic stroke. And microglia account for the largest proportion after CIRI. Previous transcriptomic studies of ischemic stroke have typically focused on the 24 hours after CIRI, obscuring the dynamics of cellular subclusters throughout the disease process. Therefore, traditional methods for identifying cell types and their subclusters may not be sufficient to fully unveil the complexity of single-cell transcriptional profile dynamics caused by an ischemic stroke. In this study, to explore the dynamic transcriptional profile of single cells after CIRI, we used scSTAR, a new bioinformatics method, to analyze the single cell transcriptional profile of day 1, 3 and 7 of transient middle cerebral artery occlusion (tMCAO) mice. Combining our bulk RNA sequence and proteomics data, we found that the Itgb2+ subclusters of microglia exhibited specific functions at three different time points after the tMCAO. Our further analysis revealed that the Itgb2+ microglia subcluster was mainly involved in energy metabolism, cell cycle, angiogenesis, neuronal myelin formation and repair at 1, 3 and 7 days after tMCAO, respectively. Our results suggested that Itgb2+ microglia act as a time-specific multifunctional immunomodulatory subcluster during CIRI, and the underlying mechanisms remain to be further investigated.

2023-03-21 | GSE227651 | GEO

Global transcriptomic profiling of ischemic/reperfusion injury in an in vivo wild-type mouse model.

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).

2011-01-10 | E-GEOD-23160 | biostudies-arrayexpress

The role of a mammalian network in regulating ischemic stroke outcome II

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

Effect of transient focal ischemia on circular RNAs

Project description:To investigate the potential involvement of circRNA in ischemic pathophysiology, we performed a circRNA microarray in an established transient middle cerebral artery occlusion (MCAO) mouse model of stroke. We evaluated the expression of 1797 circRNAs in adult mice brain after tMCAO. In our study, 5 of the 1178 circRNAs analyzed in the circRNA array were up-regulated significantly, ≥1.5-fold, in ischemic cortex at 12 hours of reperfusion after MCAO compared with their levels in sham group.

2020-09-25 | GSE115697 | GEO

Global transcriptomic profiling of ischemic/reperfusion injury in an in vivo wild-type mouse model.

2011-01-10 | GSE23160 | GEO

Proteomic alterations in microglia with ischemic stroke and effect of LPS treatment

Project description:Ischemic stroke is a common acute CNS disorder leading to nearly half a million deaths per year in Europe. The high mortality is primarily owed to the limited treatment options of restoring blood flow in a narrow time window of several hours. Furthermore, inflammatory processes in the days and weeks after ischemic stroke contribute to tissue loss and neurological deficits. The key cells that influence and control this inflammatory cascade are microglia, the innate immune cells of the CNS. Microglia can be influenced and activated by e.g. lipopolysaccharide (LPS),a bacterial cell membrane component. It has been previously shown, that repetitive LPS stimuli prior to infarction (termed immunological preconditioning) lead to reduced infarct volumina in mouse models of ischemic stroke. Furthermore, our laboratory has shown, that phosphoinositide-3 kinase gamma mediates microglial functions after LPS-preconditioning. Hence, the aim of this work was to characterize proteomic alterations in microglia with (I) ischemic stroke in general in the tMCAO (transient middle cerebral artery occlusion) mouse model of ischemic stroke, (II) the influence of LPS-preconditioning on microglial proteomic alterations after tMCAO and (III) the role of PI3Ky in the microglial proteomic changes after tMCAO and preconditioning. This was done by a single LPS injection 3 days before tMCAO in wildtype mice and mice with PI3Ky knockout or knockin of the kinase dead form of PI3Ky.

2024-03-22 | PXD031930 | Pride

Mouse CSF Analyses of middle cerebral ischemic/reperfusion (CI/R) injury followed by Buyang Huanwu Decoction

Project description:Ischemic stroke is one of the most common causes of death worldwide and a major cause of acquired disability in adults. Buyang Huanwu decoction (BHD), a traditional Chinese medicine prescription, has long been used clinically for neurological recovery after stroke. Its molecular characteristics and related biomarkers for the therapeutic effect in cerebrospinal fluid (CSF) are yet to be explored. In this project, CSF was obtained from acute ischemic stroke induced mice by a middle cerebral ischemic/reperfusion (CI/R) injury. Proteomic and metabolomic analyses of CSF were performed using LC-MS/MS to define the neuroprotective effect of BHD and the related biomarkers.

2019-02-16 | PXD006342 | Pride

Proteomic analysis of focal cerebral ischemia/reperfusion injury in rats

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

Post-ischemic ubiquitination at the postsynaptic density reversibly influences the activity of ischemia-relevant kinases.

Project description:Posttranslational modifications with ubiquitin alter protein function and stability, thereby regulating cell homeostasis and viability, particularly under stress. Ischemic stroke induces protein ubiquitination at the periphery of the ischemic territory, wherein cells remain viable. Revealing the identity of ubiquitinated proteins, their cellular location, and the functional consequences of ubiquitin modification may shed light on the role of ubiquitination in ischemic injury. Here, we employed a proteomics approach to identify proteins ubiquitinated following ischemic stroke, induced by transient middle cerebral artery occlusion (tMCAO) in mice. We detected increased ubiquitination of 198 proteins, many of which localize to the postsynaptic density (PSD) of glutamatergic neurons. Among these were proteins essential for maintaining PSD architecture, such as PSD93, PSD95 and Shank3, as well as NMDA and AMPA receptor subunits. The largest enzymatic group at the PSD with high post-ischemic ubiquitination levels were kinases, such as CaMKII, PKC, Cdk5, and Pyk2, the aberrant activity of which contributes to post-ischemic neuronal death. Concurrent phospho-proteomics revealed altered phosphorylation patterns associated with the PSD, indicative of modified PSD kinase activity following stroke. CaMKII, PKC, and Cdk5 activity was decreased while Pyk2 activity was increased at the PSD after stroke, accompanied by the hypo- and hyper-phosphorylation of downstream targets, respectively. Removal of ubiquitin restored kinases’ activity to pre-stroke levels, identifying ubiquitination as the responsible molecular mechanism for post-ischemic kinase regulation. These findings unveil a previously unrecognized role of post-ischemic ubiquitination in the regulation of essential kinases involved in ischemic injury, and presents targeting ubiquitination as a potential new avenue for the treatment of ischemic stroke.

2023-09-06 | PXD042951 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data