Microglia transcriptome in a rat model of ischemic stroke
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PROVIDER: PRJNA623992 | ENA |
REPOSITORIES: ENA
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Project description:Microglia are key regulators of inflammatory response after stroke and brain injury. Here we profiled the microglia transcriptome isolated from a spontaneously hypertensive rat model of focal cerebral ischemia. We identified an extensive and persistent upregulation of anti-inflammatory M2-like patterns after stroke and a mild up-regulation of pro-inflammatory M1-like patterns at later stage. We also found that younger brains showed larger microglial response than middle aged brains. Moreover, beyond the standard M1/M2 dichotomy, a wide spectrum of novel microglial polarization states was activated in response to stroke, particularly the phenotypes related to Tlr2 and dietary fatty acids stimulation.
2020-04-24 | GSE148350 | GEO
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
Project description:Microglia are resident myeloid cells in the central nervous system (CNS) that regulate homeostasis and protect CNS from damage and infection. The phenotype of microglia is critical in regulating the propagation and resolution of inflammatory responses after ischemic stroke. However, little is known of its complexity and heterogeneity in the above context. Here, using single-cell RNA sequencing (scRNA-seq) of over 11,000 cells from the mice ischemic brain tissues, we demonstrated a previously undefined molecular heterogeneity among microglia clusters following ischemic stroke.
2023-06-14 | GSE210986 | GEO
Project description:Microglia are resident CNS immune cells that are active sensors in healthy brain and versatile effectors under pathological conditions. Cerebral ischemia induces a robust neuroinflammatory response that includes marked changes in the gene expression and phenotypic profile of a variety of endogenous CNS cell types (astrocytes, neurons, microglia) as well as an influx of leukocytic cells (neutrophils, macrophages, T-cells) from the periphery. Many molecules and conditions can trigger a transformation of ârestingâ (or surveying) microglia to an âactivatedâ (alerted/reactive) state. Here we review recent developments in the literature that relate to microglial activation in the experimental setting of in vitro and in vivo ischemia. We also present new data from our own laboratory demonstrating the direct effects of in vitro ischemic conditions on the microglial phenotype and genomic profile. Emphasis is placed on the role of specific molecular signaling systems such as hypoxia inducible factor-1 (HIF-1) and toll-like receptor-4 (TLR4) in regulating the microglial response in this setting. We then review histological and recent novel radiological data that confirms a key role for microglial activation in the setting of ischemic stroke in humans. We discuss recent progress in the pharmacological and molecular targeting of microglia in acute ischemic stroke. Finally, we explore how recent studies on ischemic preconditioning have increased interest in preemptively targeting microglial activation in order to reduce stroke severity. 12 arrays, 4 experimental groups, 3 replicates in each group, CN is control normoxia, CH is control hypoxia, TN is TLR4 knockout normoxia, TH is TLR4 knockout hypoxia.
2010-10-05 | E-GEOD-18602 | biostudies-arrayexpress
Project description:After a stroke, the neurogenic response from the subventricular zone (SVZ) to repair the brain is limited. Microglia, as an integral part of the distinctive SVZ microenvironment, control neural stem / precursor cell (NSPC) behavior. Here, we show that discrete stroke-associated SVZ microglial clusters negatively impact the innate neurogenic response, and we propose a repository of relevant microglia–NSPC ligand–receptor pairs. After photothrombosis, a mouse model of ischemic stroke, the altered SVZ niche environment leads to immediate activation of microglia in the niche and an abnormal neurogenic response, with cell-cycle arrest of neural stem cells and neuroblast cell death. Pharmacological restoration of the niche environment increases the SVZ-derived neurogenic repair and microglial depletion increases the formation and survival of newborn neuroblasts in the SVZ. Therefore, we propose that altered cross-communication between microglial subclusters and NSPCs regulates the extent of the innate neurogenic repair response in the SVZ after stroke.
2024-09-02 | GSE275939 | GEO
Project description:The rapid accumulation of self-renewed polarized microglia in the penumbra is the critical neuroinflammatory process after the onset of ischemic stroke, leading to secondary demyelination and neuronal loss. HDAC3 has been reported to regulate cell proliferation of tumour cells and modulate neuroinflammation. However, the mechanism by which HDAC3 regulates microgliosis and microglial polarization remains ambiguous. Herein, we demonstrated that microglia-specific ablation of HDAC3 (HDAC3-miKO) ameliorated poststroke long-term functional and histological outcomes. Starting with unbiased RNA seq of microglia, we identified mitosis as the most significant process reversed by loss of HDAC3. Notably, HDAC3-miKO specifically inhibited the proliferation of M1-like microglia but not M2-like microglia, resulting in microglial transition to an M1-like state. Moreover, ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) revealed that HDAC3 deletion induced drastic closing of accessible regions enriched with motifs for PU.1. Taken together, we uncovered for the first time that HDAC3/PU.1-mediated differential proliferation-related reprogramming in different microglia populations drives poststroke inflammatory state transition of microglia and thereby contributes to the pathophysiology of ischemic stroke.
2024-03-13 | GSE220042 | GEO
Project description:The rapid accumulation of self-renewed polarized microglia in the penumbra is the critical neuroinflammatory process after the onset of ischemic stroke, leading to secondary demyelination and neuronal loss. HDAC3 has been reported to regulate cell proliferation of tumour cells and modulate neuroinflammation. However, the mechanism by which HDAC3 regulates microgliosis and microglial polarization remains ambiguous. Herein, we demonstrated that microglia-specific ablation of HDAC3 (HDAC3-miKO) ameliorated poststroke long-term functional and histological outcomes. Starting with unbiased RNA seq of microglia, we identified mitosis as the most significant process reversed by loss of HDAC3. Notably, HDAC3-miKO specifically inhibited the proliferation of M1-like microglia but not M2-like microglia, resulting in microglial transition to an M1-like state. Moreover, ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) revealed that HDAC3 deletion induced drastic closing of accessible regions enriched with motifs for PU.1. Taken together, we uncovered for the first time that HDAC3/PU.1-mediated differential proliferation-related reprogramming in different microglia populations drives poststroke inflammatory state transition of microglia and thereby contributes to the pathophysiology of ischemic stroke.
2024-03-13 | GSE220041 | GEO
Project description:To explore the impact of oxidized low density lipoprotein receptor 1 (Olr1 aka LOX-1) gene on stroke, we newly generate a LOX-1 deficient strain of the genetic background of stroke-prone spontaneously hypertensive rat (SHRSP). We explored circulatory miRNAs as diagnostic biomarkers for cerebral ischemic injury by microarray analysis in related rat strains.
2020-05-19 | E-MTAB-8389 | biostudies-arrayexpress
Project description:To explore the impact of oxidized low density lipoprotein receptor 1 (Olr1 aka LOX-1) gene on stroke, we newly generate a LOX-1 deficient strain of the genetic background of stroke-prone spontaneously hypertensive rat (SHRSP). We explored circulatory miRNAs as diagnostic biomarkers for cerebral ischemic injury by microarray analysis in related rat strains.
2020-05-19 | E-MTAB-8388 | biostudies-arrayexpress
Project description:Microglia are resident CNS immune cells that are active sensors in healthy brain and versatile effectors under pathological conditions. Cerebral ischemia induces a robust neuroinflammatory response that includes marked changes in the gene expression and phenotypic profile of a variety of endogenous CNS cell types (astrocytes, neurons, microglia) as well as an influx of leukocytic cells (neutrophils, macrophages, T-cells) from the periphery. Many molecules and conditions can trigger a transformation of “resting” (or surveying) microglia to an “activated” (alerted/reactive) state. Here we review recent developments in the literature that relate to microglial activation in the experimental setting of in vitro and in vivo ischemia. We also present new data from our own laboratory demonstrating the direct effects of in vitro ischemic conditions on the microglial phenotype and genomic profile. Emphasis is placed on the role of specific molecular signaling systems such as hypoxia inducible factor-1 (HIF-1) and toll-like receptor-4 (TLR4) in regulating the microglial response in this setting. We then review histological and recent novel radiological data that confirms a key role for microglial activation in the setting of ischemic stroke in humans. We discuss recent progress in the pharmacological and molecular targeting of microglia in acute ischemic stroke. Finally, we explore how recent studies on ischemic preconditioning have increased interest in preemptively targeting microglial activation in order to reduce stroke severity.
2010-10-05 | GSE18602 | GEO