Expression data from stroke patients brain samples
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE162955 | GEO | 2021/12/31
REPOSITORIES: GEO
Similar Datasets
Project description:1. Rationale: Stroke is still a major cause of death and disability worldwide. A better comprehension of stroke pathophysiology is fundamental to reduce its dramatic outcome. The use of high-throughput unbiased omics approaches, such as proteomics and transcriptomics, might aid to deepen the knowledge of stroke at the molecular level. Moreover, the integration of omics data is needed to depict the existing interaction between different molecular units and interpret the results in a global biological context. 2. Objective: Our aim was to identify and verify protein and gene expression changes that occur in the human brain after ischemia through an integrative approach to join and combine the information of both omics analyses. The translational potential of our results was explored in a pilot study with blood samples from ischemic stroke patients. 3. Methods and results: Proteomics and transcriptomics discovery studies were performed in human brain samples from deceased stroke patients, unveiling 128 proteins and 2716 genes significantly dysregulated after cerebral ischemia. Afterwards, integrative bioinformatics analyses joining both datasets exposed several canonical pathways altered in the ischemic area, such as neurotransmitters release or matrisome regulation, highlighting the most influential molecules in these pathways. To conduct the verification phase, 28 genes and 9 proteins were selected to be validated in independent human brain samples by means of orthogonal techniques. Our results were confirmed for NCDN, RAB3C, ST4A1, DNM1L, A1AG1, A1AT, JAM3, VTDB, ANXA1, ANXA2 and IL8. Finally, the blood circulating levels of the validated protein candidates were explored in ischemic stroke patients over the acute phase of the disease. Protein fluctuations along the first week after onset were detected for A1AG1 and A1AT. 4. Conclusion: The results presented here expand the knowledge of stroke pathology, revealing new key molecules that can be further explored as biomarkers and/or therapeutic targets of ischemic stroke.
2022-12-21 | PXD022850 | Pride
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 network-like correlation structures, we identified a set of differentially expressed genes and proteins by ischemia 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 and evaluated as potential blood biomarkers of cerebral ischemia in blood samples from ischemic and sham-control mice and from ischemic strokes and other 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 to elucidate by means of biostatistical tools key elements of the initial stages of the stroke pathophysiology, highlighting new outstanding proteins that might be further considered as blood biomarkers of ischemic stroke.
2020-09-02 | PXD016538 | Pride
Project description:Stroke is the fifth leading cause of death in the United States and is a leading cause of serious long-term disability worldwide. Innate immune responses are critical in stroke pathophysiology, and microglia are key cellular effectors in the CNS response to ischemia/reperfusion. Using a transcriptional analysis approach, we identified a robust interferon (IFN)-stimulated gene response within microglia exposed to ischemia/reperfusion. We have demonstrated that these responses are dependent on innate immune signaling components including Toll-like receptor-4 and type I IFNs. We have also elucidated several novel ischemia/reperfusion-induced microglial signaling mechanisms.
2020-04-01 | GSE107983 | GEO
Project description:Stroke remains a leading cause of death and disability worldwide. Despite continuous advances, the identification of key molecular signatures of acute ischemic stroke is still of primary interest for a real translational research on stroke diagnosis, prognosis and treatment. Integration of data
from high-throughput -omics techniques is crucial to unravel key interactions among different molecular elements in a complex biological context. Here, we used advanced data integration methods for a multi-level joint analysis of transcriptomics and proteomics datasets depicted
from the mouse brain 2h after cerebral ischemia. We identified a correlation-based integrated network of genes and proteins differentially expressed acutely after stroke. Of those, CLDN20, GADD45G, RGS2, BAG5 and CTNND2 were further evaluated as blood biomarkers of cerebral ischemia in mice and human blood samples. 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 stroke-mimicking conditions and to predict stroke patients’ poor outcome, respectively. Together, we used for the first time an integrative
biostatistical approach to elucidate key molecules of the initial stages of stroke pathophysiology and highlight new outstanding proteins that might be further considered as blood biomarkers of ischemic stroke.
2020-09-07 | PXD017280 | panorama
Project description:Stroke is a prevalent disorder representing the third leading cause of death and major cause of disability. Post-stroke epilepsy (PSE) has been recognized as a common clinical issue after stroke, accounting for 30-40% of the causes of epilepsy among older adults. In this study, we determined GABAA receptor-mediated seizure susceptibility after PT cerebral stroke in aged mice. Young adult mice around 10 weeks of age are widely used in stroke experiments. However, as most strokes are diagnosed in the elderly and PSE has been recognized as a common clinical incidence after stroke, we utilized photothrombosis (PT) model of cerebral ischemia and examined seizure susceptibility and brain injury using combined behavioral (video) and EEG monitoring and histological (MRI) assessments. To investigate GABAA receptor-mediated convulsive/non-convulsive seizures, lower-doses of pentylenetetrazol (PTZ) was injected. PTZ susceptibility in aging mice increased compared to young adults. One month after PT stroke, aged PT stroke mice exhibited severe convulsive seizures (late-onset). These findings exhibited the increase of GABAA receptor-mediated seizures susceptibility in PT stroke aging mice, but not in young adults.
2023-11-27 | GSE241528 | GEO
Project description:Acute ischemic stroke (AIS) is a leading cause of disability and mortality worldwide. By high-throughput sequencing of infarct and ischemic penumbra tissue from middle cerebral artery embolization (MCAO) mice, we identified the CircRNA expression was dramatically and selectively regulated in the penumbra tissues.
2022-11-01 | GSE186103 | GEO
Project description:Ischemic stroke is a major public health problem that is currently among the top leading causes of serious, long-term disability worldwide. The lack of effective treatment strategies prompted a search for new molecular targets for stroke prognosis and therapy. One of the epigenetic mechanisms controlling stroke progression and recovery involves signaling pathways mediated by short non-coding RNAs called microRNAs (miRNAs). Recent studies demonstrated stroke-specific changes in miRNA expression. The main goal of the present study was identify miRNAs mediating a communication between the brain and peripheral circulation in human stroke.
2023-05-31 | GSE231431 | GEO
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.
2020-09-06 | GSE137595 | GEO
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.
2013-12-09 | E-GEOD-46266 | biostudies-arrayexpress
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.
2013-12-09 | E-GEOD-46267 | biostudies-arrayexpress