Project description:We aimed to investigate the microbial community composition in patients with intracerebral hemorrhage (ICH) and its effect on prognosis. The relationship between changes in bacterial flora and the prognosis of spontaneous cerebral hemorrhage was studied in two cohort studies. Fecal samples from healthy volunteers and patients with intracerebral hemorrhage were subjected to 16S rRNA sequencing at three time points: T1 (within 24 hours of admission), T2 (3 days post-surgery), and T3 (7 days post-surgery) using Illumina high-throughput sequencing technology.
Project description:Tenuigenin (TNG), an extract obtained from Polygalae Radix, possesses anti-inflammatory,anti-oxidant, neuro-protective properties. However, the potential mechanism of TNG on intracerebral hemorrhage (ICH) has not been well studied. Therefore, in this study, we aimed to identify the prospective mechanism of TNG in treating ICH with the help of TMT-based quantitative proteomics. Our results showed that the optimal dose of TNG was 16mg/kg, which could markedly improve neurological functions, reduce cerebral edema, hematoma volume and hemoglobin level 72h after ICH. Furthermore,our proteomic results identified that a total of 404 DEPs (353 up and 51 down regulated) were identified in ICH+vehicle vs Sham group, while 342 DEPs (306 up and 36 down regulated) and 76 DEPs (28 up and 48 down regulated) were quantified in TNG vs Sham group and TNG vs ICH+vehicle group respectively. In addition, a total of 26 DEPs were selected out according to strict criteria. Complement and coagulation cascades was the most significantly enriched pathway and two proteins (MBL-C and Car1) were further validated as hub molecules.
Project description:Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder. Several studies have attempted to characterize molecular alterations associated with PTSD, but most findings were limited to the investigation of specific cellular markers in the periphery or defined brain regions. In the current study, we aimed to unravel affected molecular pathways/mechanisms in the fear circuitry associated with PTSD. We interrogated a foot shock induced PTSD mouse model by integrating proteomics and metabolomics profiling data. Alterations at the proteome level were analyzed using in vivo 15N metabolic labeling combined with mass spectrometry in prelimbic cortex (PrL), anterior cingulate cortex (ACC), basolateral amygdala (BLA), central nucleus of amygdala (CeA) and CA1 of hippocampus between shocked and non-shocked (control) mice, with and without fluoxetine treatment.
Project description:Subarachnoid hemorrhage causes an increase in inflammation and may effect neutrophils. Here, we test if there are differences in expression from neutrophils after subarachnoid hemorrhage in mice on days 1 and 3 (compared with a sham control).
Project description:Intracerebral hemorrhage (ICH) is a life-threatening condition associated with significant morbidity and mortality. Understanding the molecular mechanisms underlying ICH and its severe form is crucial for developing effective therapeutic strategies. This study investigates transcriptomic alterations in rodent models of ICH and severe intracerebral hemorrhage to shed light on the genetic pathways involved in hemorrhagic brain injury. We performed principal component analysis, revealing distinct principal component segments of normal rats compared to intracerebral hemorrhage and severe intracerebral hemorrhage rats. We further employed heatmaps and volcano plots to identify differentially expressed genes and utilized bar plots and KEGG pathway analysis to elucidate the different molecular pathways involved. Using comprehensive RNA sequencing and bioinformatics analyses, we identified a multitude of differentially expressed genes in both the ICH and severe ICH models. Our results revealed 5679 common genes among the normal, intracerebral hemorrhage, and severe intracerebral hemorrhage groups in the upregulated genes group, and 1196 common genes in the downregulated genes. A volcano plot comparing the groups further highlighted common genes, including PDPN, TIMP1, SERPINE1, TUBB6, and CD44. These findings underscore the complex interplay of genes involved in inflammation, oxidative stress, and neuronal damage. Furthermore, pathway enrichment analysis uncovered key signaling pathways, including the TNF signaling pathway, protein processing in the endoplasmic reticulum, MAPK signaling pathway, and Fc gamma R-mediated phagocytosis, implicated in the pathogenesis of ICH.
Project description:Cognitive dysfunction (CD) in heart failure (HF) adversely affects treatment compliance and quality of life. Although, ryanodine receptor type 2 (RyR2) has been linked to cardiac muscle dysfunction, its role in CD remains unclear. Here, we show in hippocampal neurons from patients and mice with HF that the ryanodine receptor type 2 (RyR2)/intracellular Ca 2+ release channels were post-translationally modified (PTM) and leaky. RyR2 PTM was caused by hyper-adrenergic stress and activation of the transforming growth factor (TGF-β) pathway. HF mice treated with either a RyR2 stabilizer drug (S107), beta-blocker (propranolol) or TGF-β inhibitor (SD-208), or mice insensitive RyR2 Ca 2+ leak (RyR2-S2808A), were protected against HF-induced CD. Taken together, we propose that HF is a systemic illness that include cardiogenic dementia, and intracellular Ca 2+ leak is a common effector in multiple components of HF.
Project description:This project investigates transcriptomic changes in experimental models of intracerebral hemorrhage (ICH) in rats. Bulk RNA sequencing was performed on perihematomal brain tissue collected 3 days after ICH induction in three groups: common hemorrhage (IC), severe hemorrhage (IS), and severe hemorrhage with hematoma aspiration (IS-HA).
Project description:Extracellular vesicles (EVs) participate in cell-to-cell paracrine signaling and can be biomarkers of the pathophysiological processes underlying disease. In intracerebral hemorrhage (ICH), the study of the number and molecular content of circulating EVs may help elucidate the biological mechanisms involved in damage and repair, contributing valuable information to the identification of new therapeutic targets. The objective of this study was to describe the number and protein content of blood-derived EVs following an ICH in an animal model in rats. The protein content in the EVs was analyzed by mass spectrometric data-dependent acquisition; protein quantification was obtained by sequential window acquisition of all theoretical mass spectra data and compared at pre-defined time points.
Project description:We tested the hypothesis that circulating microRNAs (miRNAs) present in plasma might display a specific signature in patients with intracerebral hemorrhage (ICH). Global miRNA profiles were determined with the Agilent Human miRNA Microarray platform, 027233. ICH patients display a characteristic inflammation-related miRNA profile as compared to healthy controls. Plasma samples were collected from the following 6 subject groups: male ICH patients (n=8), female ICH patients (n=7), male healthy control (n=4), female healthy control (n=4), male ischemic stroke patients (n=8) and female ischemic stroke patients (n=8). Total RNAs isolated from 1 ml plasma were pooled for each group. A fixed volume of RNA sample was withdrawn from each pool and used for microarray detection.
Project description:To investigate age-dependent transcriptomic changes between young or aged intracerebral hemorrhage mice, we established collagenase IV-induced intracerebral hemorrhage mice models. Intracerebral hemorrhage was induced by infusion of sterile collagenase IV in ipsilateral caudate putamen of brain. We then performed gene expression profiling analysis using data obtained from RNA-seq of brain perihematomal tissues from young or aged ICH mice 24 hours after intracerebral hemorrhage.