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Project description:The effect of Gelsevirine on ischemia penumbra
| PRJNA881748 | ENA
Project description:Cerebral ischemia, commonly resulting from an ischemic stroke, can lead to significant cognitive impairments due to neuronal damage and neuroinflammation. The cannabinoid CB1 receptor, part of the endocannabinoid system, plays a crucial role in modulating synaptic plasticity, neurogenesis, and neuroprotection. Research suggests that targeting the CB1 receptor could offer a promising therapeutic strategy to mitigate cognitive deficits following cerebral ischemia. Modulating CB1 receptor activity, either through agonists or antagonists, has been shown to influence key pathways involved in neuroprotection and inflammation, potentially enhancing recovery of cognitive functions. Understanding the mechanisms by which CB1 receptor modulation affects brain recovery post-ischemia could pave the way for novel treatments aimed at reducing the long-term cognitive impact of ischemic strokes.
2024-07-07 | PXD053731 |
Project description:Ischemic injuries will lead to necrotic tissue damage, and post-ischemia angiogenesis plays critical roles in blood flow restoration and tissue recovery. Recently, several types of small RNAs have been reported to be involved in this process. In this study, we first generated a rat brain ischemic model to investigate the involvement of new types of small RNAs in ischemia. We utilized deep sequencing and bioinformatics analyses to demonstrate that the level of small RNA fragments derived from tRNAs was strikingly up-regulated in the ischemic rat brain. Among these sequences, tRNAVal- and tRNAGly-derived small RNAs account for the most abundant segments. The up-regulation of tRNAVal- and tRNAGly-derived fragments was verified through northern blot and quantitative PCR analyses. The levels of these two fragments also increased in a mouse hindlimb ischemia model and cellular hypoxia model. Importantly, the overexpression of tRNAVal- and tRNAGly-derived fragments in endothelial cells inhibited cell proliferation, migration and tube formation. Our results indicate that tRNA-derived fragments are involved in tissue ischemia, and we demonstrate for the first time that tRNAVal- and tRNAGly-derived fragments inhibit angiogenesis by modulating the function of endothelial cells. Examine small RNAs involved in post-ischemia angiogenesis
2016-03-16 | E-GEOD-70473 | biostudies-arrayexpress
Project description:<p>Buyang Huanwu decoction (BHD) is a well-known Chinese herbal prescription. It has been widely used in the clinical treatment of cerebral ischemia (CI) in China. However, the mechanism underlying the treatment of CI with BHD remains to be elucidated. In this study, we combined microbiomic and metabolomic strategies to explore the therapeutic effects of BHD on middle cerebral artery occlusion (MCAO) in rats. Our results showed that BHD could effectively improve neurological severity scores and alleviate neuronal damage in rats with MCAO. BHD could also reduce the level of peripheral proinflammatory cytokines and inhibit neuroinflammation. 16S rRNA sequencing showed that BHD could increase the relative abundances of the genera Lactobacillus, Faecalibacterium, Ruminococcaceae_UCG-002, etc., while decreasing the relative abundances of the genera Escherichia-Shigella, Klebsiella, Streptococcus, Coprococcus_2, Enterococcus, etc. Untargeted metabolomic analysis of hippocampal samples showed that 17 significantly differentially abundant metabolites and 9 enriched metabolic pathways were linked with BHD treatment. We also found that the regulatory effects of BHD on metabolites were correlated with the differentially abundant microbial taxa. The predicted function of the gut microbiota and the metabolic pathway enrichment results showed that purine metabolism, glutamatergic synapses, arginine and proline metabolism, and alanine, aspartic acid and glutamate metabolism were involved in the effects of BHD. These pathways may be related to pathological processes such as excitotoxicity, neuroinflammation, and energy metabolism disorder in CI. In summary, these findings suggest that regulation of hippocampal metabolism and of the composition and function of the gut microbiota may be important mechanisms underlying the effect of BHD in the treatment of CI.</p>
2022-06-02 | MTBLS4366 | MetaboLights
Project description:Immune responses and neuroinflammation occurring after acute ischemic stroke (AIS) are closely related to brain injury. Histone lactylation is a metabolic stress-related histone modification that participates in the pathogenesis of various diseases. However, the role of histone regulation in cerebral ischemic stroke remains unknown. In this study, a transient middle cerebral artery occlusion (tMCAO/R) model and an oxygen–glucose deprivation and reoxygenation (OGD/R) model were used to simulate in vivo/in vitro ischemia–reperfusion injury. The underlying mechanism of microglial histone lactylation was investigated using microglia-specific SMEK1-overexpressing mice and BV2 cells. The results showed that lactate overload resulted in elevated histone lactylation after AIS. Decreased SMEK1 expression in microglia after ischemic stroke was associated with increased lactate levels and subsequent neuroinflammation. Microglia-specific SMEK1 deficiency in microglia after ischemia can promote lactate production by inhibiting the pyruvate dehydrogenase kinase 3-pyruvate dehydrogenase (PDK3-PDH) pathway. Specifically, H3 lysine 9 lactylation (H3K9la) activated Ldha and Hif-1α transcription in microglia and promoted glycolysis. SMEK1-overexpressing mice exhibited better neurologic recovery after ischemic stroke than control mice. Mechanistically, we provided new evidence that microglial histone lactylation promoted glycolysis in ischemia‒reperfusion injury and elucidated the potential role of SMEK1 as an upstream regulatory molecule in histone lactylation after cerebral ischemia. According to our results, microglial SMEK1 may be potential therapeutic targets for AIS.
2025-01-02 | GSE283233 | GEO
Project description:Histamine is catalyzed by histidine decarboxylase (HDC), which plays important roles in many physiological and pathological processes, but its role in angiogenesis has not been thoroughly clarified. Here we report that HDC is highly expressed in Ly6C+macrophages, rather than in endothelial cells using Hdc-GFP transgenic mice with hindlimb ischemia (HLI) mouse model. Given the whole-process promoting effect of macrophages on angiogenesis, a cluster of HDC+CXCR2+ macrophages have been identified by single-cell sequencing technology in ischemic tissue. The inactivation of HDC leads to a lack of histamine and pro-angiogenic factor production in macrophages, inducing a harsh inflammatory microenvironment that is not conducive to the interaction between macrophages and endothelial cells. Moreover, HA-DA@histamine hydrogel has been designed and demonstrated to safely treat ischemic injury by modulating inflammation and angiogenesis. These data highlight the critical roles of HDC/histamine signaling in macrophage differentiation, angiogenesis, and muscle regeneration in the early stage of HLI.
2024-08-02 | GSE273730 | GEO
Project description:Ischemic injuries will lead to necrotic tissue damage, and post-ischemia angiogenesis plays critical roles in blood flow restoration and tissue recovery. Recently, several types of small RNAs have been reported to be involved in this process. In this study, we first generated a rat brain ischemic model to investigate the involvement of new types of small RNAs in ischemia. We utilized deep sequencing and bioinformatics analyses to demonstrate that the level of small RNA fragments derived from tRNAs was strikingly up-regulated in the ischemic rat brain. Among these sequences, tRNAVal- and tRNAGly-derived small RNAs account for the most abundant segments. The up-regulation of tRNAVal- and tRNAGly-derived fragments was verified through northern blot and quantitative PCR analyses. The levels of these two fragments also increased in a mouse hindlimb ischemia model and cellular hypoxia model. Importantly, the overexpression of tRNAVal- and tRNAGly-derived fragments in endothelial cells inhibited cell proliferation, migration and tube formation. Our results indicate that tRNA-derived fragments are involved in tissue ischemia, and we demonstrate for the first time that tRNAVal- and tRNAGly-derived fragments inhibit angiogenesis by modulating the function of endothelial cells.
2016-03-16 | GSE70473 | GEO
Project description:Background–Acute coronary syndrome (ACS) is sometimes accompanied by accelerated coagulability, lipid metabolism, and inflammatory responses, which are not attributable to the cardiac events alone. We hypothesized that the liver plays a pivotal role in the pathophysiology of ACS. We simultaneously analyzed the gene expression profiles of the liver and heart during acute myocardial ischemia in mice. Methods and Results–Mice were divided into three treatment groups: sham-operation, ischemia-reperfusion (I/R), and myocardial infarction. Mice with liver I/R were included as additional controls. Marked changes in hepatic gene expression were observed after 24 hours, despite the lack of histological changes in the liver. Genes related to tissue remodeling, adhesion molecules, and morphogenesis were significantly upregulated in the livers of mice with myocardial I/R or infarction, but not in those with liver I/R. Myocardial ischemia, but not changes in the hemodynamic state, was postulated to significantly alter hepatic gene expression. Moreover, detailed analysis of the signaling pathway suggested the presence of humoral factors that intervened between the heart and liver. To address these points, we utilized isolated primary hepatocytes and showed that osteopontin released from the heart actually altered the signaling pathways of primary hepatocytes to those observed in the livers of mice under myocardial ischemia. Moreover, osteopontin stimulated primary hepatocytes to secrete vascular endothelial growth factor-A, which is important for tissue remodeling. Conclusions– Hepatic gene expression is potentially regulated by cardiac humoral factors under myocardial ischemia. These results provide new insights into the pathophysiology of ACS.
2009-11-12 | GSE14843 | GEO
Project description:Background and Purpose: Long noncoding RNAs (lncRNAs) are an emerging class of genomic regulatory molecules reported in neurodevelopment and many diseases. Despite extensive studies have identified lncRNAs and discovered their functions in CNS diseases, the function of lncRNAs in ischemia stroke remains poorly understood. Method: Ischemia was induced by transient middle cerebral artery occlusion. Expression profiles of lncRNAs, miRNAs and mRNAs after ischemia stroke were obtained using high throughput sequencing technology. A correlation network was constructed to predict lncRNA functions. LncRNA-miRNA-mRNA network was constructed to discover ceRNAs. Results: 1924 novel lncRNAs were identified, indicating that the ischemia stroke has a complex effect on lncRNAs. The top 10 regulated lncRNAs was validated by qRT-PCR. We have also predicted function of lncRNAs, and subjected them to gene co-expression network analysis, revealing the involvement of lncRNAs in many important biological process including injury and repair that are implicated in the regulation of ischemia stroke. Furthermore, lncRNAs mediated SMD (Staufen1-mediated mRNA decay) was analyzed and ceRNA (competitive endogenous RNAs) network was constructed in ischemia stroke. Conclusions: This study reports the genome-wide lncRNA profiles in ischemia stroke using high throughput sequencing and constructs a systematic lncRNA-miRNA-mRNA network which reveals a complex functional noncoding RNA regulatory network in ischemia stroke.
2017-02-23 | GSE78200 | GEO
Project description:Microarray analysis of differentially expressed genes from rats undergoing placental ischemia versus health controls Placental ischemia is believed to be an important contributor to human preeclampsia, though the targets induced by the ischemia remain unclear.
2013-09-05 | GSE50596 | GEO