Gene expression profile at single cell level from the brain at 3h, 2d, and 7d after hypoxic ischemic encephalopathy
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE273044 | GEO | 2025/06/15
REPOSITORIES: GEO
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Project description:Neonatal hypoxic ischemic encephalopathy (HIE) occurs in 1.5 per 1000 live births, leaving affected children with long-term motor and cognitive deficits. Few animal models of HIE incorporate maternal immune activation (MIA) despite the significant risk MIA poses to HIE incidence and diagnosis. Our non-invasive model of HIE pairs late gestation MIA with postnatal hypoxia. HIE pups exhibited a trend toward smaller overall brain size and delays in the ontogeny of several developmental milestones. In adulthood, HIE animals had reduced strength and gait deficits, but no difference in speed. Surprisingly, HIE animals performed better on the rotarod, an assessment of motor coordination. There was significant upregulation of inflammatory genes in microglia 24 hours after hypoxia, which were largely downregulated one week later. Single cell RNAseq revealed upregulation of epigenetic machinery in macrophages invading the brain following HIE. These results support a two-hit noninvasive model pairing MIA and hypoxia as a model for HIE in humans. This model results in a mild phenotype compared to established HIE models; however, HIE is a clinically heterogeneous injury resulting in a variety of outcomes in humans. The pathways identified in our model of HIE may yield novel targets for therapy for neonates with HIE.
2024-10-02 | GSE275712 | GEO
Project description:Neonatal hypoxic ischemic encephalopathy (HIE) occurs in 1.5 per 1000 live births, leaving affected children with long-term motor and cognitive deficits. Few animal models of HIE incorporate maternal immune activation (MIA) despite the significant risk MIA poses to HIE incidence and diagnosis. Our non-invasive model of HIE pairs late gestation MIA with postnatal hypoxia. HIE pups exhibited a trend toward smaller overall brain size and delays in the ontogeny of several developmental milestones. In adulthood, HIE animals had reduced strength and gait deficits, but no difference in speed. Surprisingly, HIE animals performed better on the rotarod, an assessment of motor coordination. There was significant upregulation of inflammatory genes in microglia 24 hours after hypoxia, which were largely downregulated one week later. Single cell RNAseq revealed upregulation of epigenetic machinery in macrophages invading the brain following HIE. These results support a two-hit noninvasive model pairing MIA and hypoxia as a model for HIE in humans. This model results in a mild phenotype compared to established HIE models; however, HIE is a clinically heterogeneous injury resulting in a variety of outcomes in humans. The pathways identified in our model of HIE may yield novel targets for therapy for neonates with HIE.
2024-10-02 | GSE274183 | GEO
Project description:Long noncoding RNAs (lncRNA) have been proved to participate in many biological processes. To investigate the expression profile of lncRNAs and their potential functions in neonatal hypoxic ischemic encephalopathy (HIE). We detected the lncRNA and mRNA expression in the peripheral blood samples in HIE and relative control using microarray. A total of 376 lncRNAs and 126 mRNAs were detected to be differentially expressed between HIE and the non-HIE samples (fold change>2). Quantitative real-time PCR were used to validation of microarray data. Gene ontology (GO) enrichment and KEGG pathway analysis were used to determine the gene function. Furthermore, the co-expression network of lncRNA-mRNA were conducted to predicted the potential the targets of lncRNAs. In conclusion, our study first demonstrated the differentially expression profile of lncRNAs in the whole blood of neonatal HIE and may provide a new view of distinct lncRNAs functions in HIE.
2019-11-05 | GSE121178 | GEO
Project description:Hypoxic-ischemic encephalopathy (HIE) encompasses brain injuries resulting from reduced or interrupted oxygen or blood flow to the brain before, during, or immediately after birth. During the acute phase, neuronal damage is driven by excitotoxicity, with permanent injury manifesting over the subsequent hours. Current treatment options have limited efficacy, underscoring the need for deeper insights into HIE pathogenesis and the development of novel therapeutic strategies. Recent advances in single-cell RNA sequencing (snRNA-seq) have enabled molecular investigations of diverse diseases. However, the large size of neurons has posed challenges in studying conditions where neuronal damage is central. To address this, we employed snRNA-seq to evaluate region-specific neuronal damage in a mouse model of HIE. Our HIE model was established in postnatal day-7 mice, with cortical and hippocampal tissues harvested from the ipsilesional side one week post-injury. Analysis revealed pronounced changes in the hippocampus, especially in the CA1 region, with a significant reduction in neuronal populations in the affected hemisphere. These alterations were specific to combined hypoxic-ischemic conditions and were not observed with hypoxia or ischemia alone. In contrast, changes in the cerebral cortex were less prominent. Transcriptomic analysis showed similar gene expression patterns in the cortex and hippocampus of the HIE group, including the identification of genes related to viral response pathways, suggesting a potential link to interferon activation. These findings provide valuable insights into the molecular and anatomical impact of HIE and highlight the hippocampus as a critical focus for understanding disease mechanisms and therapeutic development.
2025-04-24 | GSE284245 | GEO
Project description:Gene expression profile at single cell level from the brain at 3h, 2d, and 7d after hypoxic ischemic encephalopathy
| PRJNA1139835 | ENA
Project description:Hypoxic-Ischemic Encephalopathy (HIE) is one of the most relevant contributors to neurological disability in term infants. We hypothesized that clinical outcomes of newborns with (HIE) can be associated with changes at plasma metabolic level enabling the detection of brain injury. Plasma samples of a cohort of 55 asphyxiated infants who evolved to moderate/severe HIE were collected between birth and completion of therapeutic hypothermia (TH). Samples were analyzed employing a quantitative gas chromatography-mass spectrometry method for the determination of lactate and pyruvate and an untargeted liquid chromatography-time-of-flight mass spectrometry method for metabolic fingerprinting. Brain injury was assessed employing magnetic resonance imaging (MRI). A critical assessment of the usefulness of lactate, pyruvate, and pyruvate/lactate for outcome prediction was carried out. Besides, metabolic fingerprinting identified a dynamic perturbation of eleven metabolic pathways, including amino acid and purine metabolism, and the steroid hormone biosynthesis, in newborns with pathologic MRI outcomes. Although data suggest the usefulness of lactate and pyruvate monitoring during 72 h for discerning outcomes, only the steroid hormone biosynthesis pathway was significantly altered in early plasma samples (i.e., before the initiation of TH). This study highlights pathways that might potentially be targeted for biomarker discovery or adjuvant therapies to be combined with TH.
2021-11-09 | MTBLS1041 | MetaboLights
Project description:Hypoxic ischemic encephalopathy (HIE) is a primary cause of neonatal death and disabilities resulting from perinatal hypoxia. The progression of HI injury is closely associated with neuroinflammation. Therefore, suppressing inflammatory pathways is a promising therapeutic strategy for treating HIE. Echinatin (Ech) is a principal active component of glycyrrhiza, with anti-inflammatory and anti-oxidative effects, often combined with other herbs to exert effects of clearing heat and detoxifying. This study aimed to investigate the anti-inflammatory and neuroprotective effects of Ech on neonatal rats with hypoxic-ischemic brain damage and on PC12 cells induced by oxygen-glucose deprivation (OGD).
2024-05-07 | GSE266886 | GEO
Project description:Hepatic Encephalopathy is the brain disorder caused by liver damage, characterized by cognitive and motor impairments. Glutamate a predominant excitatory neurotransmitter over activate post-synaptic neuron via NMDAR receptors leads to neuronal derangement. NMDAR as a therapeutic target is not viable option due to its crucial role in brain physiology. In order to discover new non-NMDAR therapeutic targets high resolution mass spectrometry (HRMS) technique was used for proteomic profiling of the hippocampal proteins in Moderate hepatic encephalopathy (MoHE) rat model.
2024-05-27 | PXD036723 | Pride
Project description:Hepatic encephalopathy (HE) is a common complication of liver cirrhosis, associated with high morbidity and mortality, for which no brain-targeted therapies exist at present. The interplay between hyperammonemia and inflammation is thought to drive HE development. As such, astrocytes, the most important ammonia-metabolizing cells in the brain, and microglia, the main immunomodulatory cells in the brain, have been heavily implicated in HE development. As insight into cellular perturbations driving brain pathology remains largely elusive, we aimed to investigate cell-type specific transcriptomic changes in the HE brain. In the recently established mouse bile duct ligation (BDL) model of HE, we performed RNA-Seq of sorted astrocytes and microglia at 14 and 28 days after induction. This revealed a marked transcriptional response in both cell types which was most pronounced in microglia. In both cell types, pathways related to inflammation and hypoxia, mechanisms commonly implicated in HE, were enriched. Additionally, astrocytes exhibited increased corticoid receptor and oxidative stress signaling, whereas microglial transcriptome changes were linked to immune cell attraction. Accordingly, both monocytes and neutrophils accumulated in the BDL mouse brain. Time-dependent changes were limited in both cell types, suggesting early establishment of a pathological phenotype. While HE is often considered a unique form of encephalopathy, astrocytic and microglial transcriptomes showed significant overlap with previously established gene expression signatures in other neuroinflammatory diseases like septic encephalopathy and stroke, suggesting common pathophysiological mechanisms. Our dataset identifies key molecular mechanisms involved in preclinical HE and provides a valuable resource for development of novel glial-directed therapeutic strategies.
2023-05-30 | GSE230287 | GEO
Project description:Neonatal hypoxic–ischemic encephalopathy (HIE) results in neurological impairments; cell-based therapy has been suggested as a therapeutic avenue. Previous research has demonstrated the synergistically potentiated therapeutic efficacy of human umbilical cord blood (UCB) by combining recombinant human erythropoietin (EPO) treatment for recovery from HIE. However, its molecular mechanism is not entirely understood. In the present study, we analyzed the mechanisms underlying the effect of combination treatment with EPO and UCB by transcriptomic analysis, followed by gene enrichment analysis. The HIE model of the neonate was prepared and randomly divided into five groups: sham, HIE, and UCB, EPO, and UCB+EPO treatments after HIE. A total of 376 genes were differentially expressed when |log2FC| ≥ 1-fold change expression values were considered to be differentially expressed between UCB+EPO and HIE. Further assessment through qRT-PCR and gene enrichment analysis confirmed the expression and correlation of its potential target Gene N as an essential gene involved in the synergistic effect of the UCB+EPO combination.
2025-02-10 | GSE196570 | GEO