title: Gene expression profiling of brain cortex microvessels may support brain vasodilation in acute liver failure rat models.
abstract: Development of brain edema in acute liver failure can increase intracranial pressure, which is a severe complication of the disease. However, brain edema is neither entirely cytotoxic nor vasogenic and the specific action of the brain microvasculature is still unknown. We aimed to analyze gene expression of brain cortex microvessels in two rat models of acute liver failure. In order to identify global gene expression changes we performed a broad transcriptomic approach in isolated brain cortex microvessels from portacaval shunted rats after hepatic artery ligation (HAL), hepatectomy (HEP), or sham by array hybridization and confirmed changes in selected genes by RT-PCR. We found 157 and 270 up-regulated genes and 143 and 149 down-regulated genes in HAL and HEP rats respectively. Western blot and immunohistochemical assays were performed in cortex and ELISA assays to quantify prostaglandin E metabolites were performed in blood of the sagittal superior sinus. We Identified clusters of differentially expressed genes involving inflammatory response, transporters-channels, and homeostasis. Up-regulated genes at the transcriptional level were associated with vasodilation (prostaglandin-E synthetase, prostaglandin-E receptor, adrenomedullin, bradykinin receptor, adenosine transporter), oxidative stress (hemoxygenase, superoxide dismutase), energy metabolism (lactate transporter) and inflammation (haptoglobin). The only down-regulated tight junction protein was occludin but slightly. Prostaglandins levels were increased in cerebral blood with progression of liver failure. In conclusion, in acute liver failure, up-regulation of several genes at the level of microvessels might suggest an involvement of energy metabolism accompanied by cerebral vasodilation in the cerebral edema at early stages.
authors.affiliation: Servei de Medicina Interna-Hepatologia, Valld'Hebron Institut de Recerca (VH-IR), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.|Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Lluis
authors.initials: L
authors.lastname: Palenzuela
authors.affiliation: Servei de Medicina Interna-Hepatologia, Valld'Hebron Institut de Recerca (VH-IR), Barcelona, Spain. marc.oria@cchmc.org.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. marc.oria@cchmc.org.|Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain. marc.oria@cchmc.org.|Center for Fetal, Cellular and Mollecular Therapy, Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH, USA. marc.oria@cchmc.org.
authors.forename: Marc
authors.initials: M
authors.lastname: Oria
authors.affiliation: Servei de Medicina Interna-Hepatologia, Valld'Hebron Institut de Recerca (VH-IR), Barcelona, Spain.|Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Romero-Giménez
authors.affiliation: Servei de Medicina Interna-Hepatologia, Valld'Hebron Institut de Recerca (VH-IR), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.|Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Garcia-Lezana
authors.affiliation: Servei de Medicina Interna-Hepatologia, Valld'Hebron Institut de Recerca (VH-IR), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.|Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Chavarria
authors.affiliation: Servei de Medicina Interna-Hepatologia, Valld'Hebron Institut de Recerca (VH-IR), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.|Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Cordoba
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods*; D017114:Liver Failure, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D055806:Microvessels / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000502:physiology*
keywords: Acute liver failure; Blood-brain-barrier; Brain edema; Gene expression; Microvessels