title: Endothelin B receptor-mediated encephalopathic events in mouse sepsis model.
abstract: OBJECTIVE
  We evaluated whether pathophysiological events in the brain in sepsis are mediated by ET-1/ETB receptor axis.
  
  
  METHODS
  We prepared raw fecal fluid from soft stool of mice. Mice were randomly divided into three groups: pre-PBS+raw fecal fluid group (Sepsis, easy stool method (ESM) group); pre-BQ788+raw fecal fluid group (BQ group); and pre-BQ788+PBS group (PBS group). According to each experimental condition, PBS or BQ788 was intravenously injected into mice prior to intraperitoneal administration of fecal fluid or PBS. All groups of mice were sacrificed at 8h after administration, and then brain samples were prepared.
  
  
  RESULTS
  In the ESM group, an increase of apoptotic neuroblasts was demonstrated in the subgranular zone of the hippocampal dentate gyrus, enhanced expression of c-FOS was observed in arginine-vasopressin-containing neurons in the hypothalamic paraventricular nucleus, and various cytokines involving TNF-α were upregulated in the brain, compared with those in the PBS group. In the region corresponding to their findings, the number of reactive microglia and vascular leakage was markedly increased. BQ788 inhibited the induction of c-FOS expression, neuroblast apoptosis, cytokine upregulation and reactive microglia without affecting vascular leakage.
  
  
  CONCLUSIONS
  We demonstrated that BQ788 could protect the brain from the following sepsis-associated pathophysiological output: neural cell death, inflammatory response and the Hans Selye's environmental stress reaction.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Kento
authors.initials: K
authors.lastname: Yoshioka
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tatsumi
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Sadao
authors.initials: S
authors.lastname: Kimura
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan. Electronic address: kasuya@faculty.chiba-u.jp.
authors.forename: Yoshitoshi
authors.initials: Y
authors.lastname: Kasuya
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000150:complications* / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D055099:Neuroendocrine Cells / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D044023:Receptor, Endothelin B / Q000378:metabolism*; D018805:Sepsis / Q000150:complications* / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D044023:Receptor, Endothelin B
keywords: BQ788; Brain stem/progenitor cells; Hypothalamic–pituitary–adrenal axis; Sepsis-associated encephalopathy