Project description:To further identify the fecal miRNAs generated in HE, we conducted an miRNA microarray analysis on feces collected from patients with HE and CHB. The microarray analysis of miRNA expression profiles revealed that the abundance of 10 miRNAs was significantly increased in feces from patients with HE, as compared with that from patients with CHB, whereas the abundance of 8 miRNAs was decreased.
Project description:Identify differentially expressed genes related to the neurodegenerative process in a new animal model of hepatic encephalopathy (HE). The animal model consists on the simulation of several bouts of HE in PCA rats, being the precipitant factors of the episodes ammonia (NH3) and/or lipopolisaccharide (LPS) or saline.
Project description:Identify differentially expressed genes related to the neurodegenerative process in a new animal model of hepatic encephalopathy (HE). The animal model consists on the simulation of several bouts of HE in PCA rats, being the precipitant factors of the episodes ammonia (NH3) and/or lipopolisaccharide (LPS) or saline. Regular administration (one every two weeks up to 10 infussion) of NH3 (20 μl/min along 3h) and/or LPS (5mg/kg) or in PCA rats. Sham rats were used as a surgery control.
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.
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.