title: Gene expression profiling in the cerebral cortex of patients with cirrhosis with and without hepatic encephalopathy.
abstract: Hepatic encephalopathy (HE) is a frequent complication of liver cirrhosis and is seen as the clinical manifestation of a low-grade cerebral edema associated with oxidative-nitrosative stress. However, comprehensive data on HE-associated molecular derangements in the human brain are lacking. In the present study, we used a whole human genome microarray approach for gene expression profiling in post mortem brain samples from patients with cirrhosis with or without HE and controls without cirrhosis. Altered expression levels were found for a total of 1,012 genes in liver cirrhosis patients without and with HE, and HE-characteristic gene expression changes were identified. Genes with altered expression pattern in HE were related to oxidative stress, microglia activation, receptor signaling, inflammatory pathways, cell proliferation, and apoptosis. Despite an up-regulation of genes associated with microglia activation, pro-inflammatory cytokine messenger RNA profiles remained unchanged in the brains of patients with liver cirrhosis and HE compared with controls. Interestingly, many genes counteracting pro-inflammatory signaling and inflammatory cytokine expression were up-regulated in the cerebral cortex of patients with liver cirrhosis and HE.
  
  
  CONCLUSIONS
  Pathogenetic mechanisms of HE deduced from cell culture and animal experiments, such as oxidative stress, altered Zn(2+) homeostasis and microglia activation also apply to human brain from patients with liver cirrhosis and HE. The study also revealed a not-yet recognized increased expression of genes antagonizing proinflammatory signaling and inflammatory cytokine expression. (HEPATOLOGY 2013;57:2436-2447).
authors: Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich-Heine University, Düsseldorf, Germany.
authors: Boris
authors: B
authors: Görg
authors: Hans-Jürgen
authors: HJ
authors: Bidmon
authors: Dieter
authors: D
authors: Häussinger
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D016022:Case-Control Studies; D002454:Cell Differentiation; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006501:Hepatic Encephalopathy / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000502:physiology; D008875:Middle Aged; D018384:Oxidative Stress