title: Hippocampal transcriptional dysregulation after renal ischemia and reperfusion.
abstract: Neurological complications contribute largely to the morbidity and mortality in patients with acute renal failure. In order to study pathophysiological complications of renal failure, a murine model of renal ischemia/reperfusion-induced acute kidney injury (AKI) was generated by 60min bilateral ischemia, and followed by 2h or 24h reperfusion (B-60'IRI). Compared to the sham-operated mice, B-60'IRI mice exhibited a significant inflammatory injury to remote brain. We found that serum and brain levels of KC, G-CSF and MCP-1 were significantly increased in B-60'IRI mice after 2h and 24h reperfusion when compared with sham-operated mice. Moreover, B-60'IRI mice exhibited increased numbers of activated microglial cells in the brain, and severe blood-brain barrier (BBB) permeability when compared with the control sham mice. The technology of cDNA microarray and quantitated RT-PCR are used to identify hippocampal genes whose expression is altered in response to AKI in B-60' IRI mice. The initiation of transcriptional abnormality was indicated by the finding that B-60' IRI mice exhibited upregulated mRNA levels of genes involved in inflammation, cell signaling, extracellular matrix and cell-cycle regulation and downregulated mRNA levels of genes involved in transporters, G protein-coupled receptor signaling, cell survival and chaperone. Our data suggest that renal IR contributes to a complicated hippocampal gene irregulation in inflammation and physiological homeostasis.
authors.affiliation: Department of Anesthesiology, Chang Gung Memorial Hospital, Linkou, Taipei, Taiwan, ROC; Transgenic & Molecular Immunogenetics Laboratory, Chang Gung Memorial Hospital, Linkou, Taipei, Taiwan, ROC; Department of Medicine, Chang Gung University, Linkou, Taipei, Taiwan, ROC.
authors.forename: An-Hsun
authors.initials: AH
authors.lastname: Chou
authors.affiliation: Department of Medical Research and Development, Chang Gung Memorial Hospital, Linkou, Taipei, Taiwan, ROC.
authors.forename: Chiou-Mei
authors.initials: CM
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology, Chang Gung Memorial Hospital, Linkou, Taipei, Taiwan, ROC; Transgenic & Molecular Immunogenetics Laboratory, Chang Gung Memorial Hospital, Linkou, Taipei, Taiwan, ROC; Department of Medicine, Chang Gung University, Linkou, Taipei, Taiwan, ROC.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Chang Gung Memorial Hospital, Linkou, Taipei, Taiwan, ROC; Transgenic & Molecular Immunogenetics Laboratory, Chang Gung Memorial Hospital, Linkou, Taipei, Taiwan, ROC; Department of Medicine, Chang Gung University, Linkou, Taipei, Taiwan, ROC.
authors.forename: Jiin-Tarng
authors.initials: JT
authors.lastname: Liou
authors.affiliation: Department of Anesthesiology, Chang Gung Memorial Hospital, Linkou, Taipei, Taiwan, ROC; Transgenic & Molecular Immunogenetics Laboratory, Chang Gung Memorial Hospital, Linkou, Taipei, Taiwan, ROC; Department of Medicine, Chang Gung University, Linkou, Taipei, Taiwan, ROC.
authors.forename: Fu-Chao
authors.initials: FC
authors.lastname: Liu
authors.affiliation: Chang Gung University of Science and Technology, Gueishan, Taoyuan, Taiwan, ROC.
authors.forename: Ying-Ling
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Chang Gung Memorial Hospital, Linkou, Taipei, Taiwan, ROC; Transgenic & Molecular Immunogenetics Laboratory, Chang Gung Memorial Hospital, Linkou, Taipei, Taiwan, ROC; Department of Medicine, Chang Gung University, Linkou, Taipei, Taiwan, ROC; Department of Medical Research and Development, Chang Gung Memorial Hospital, Linkou, Taipei, Taiwan, ROC. Electronic address: yd3j@cgmh.org.tw.
authors.forename: Yuan-Ji
authors.initials: YJ
authors.lastname: Day
mesh_terms: D058186:Acute Kidney Injury / Q000503:physiopathology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000503:physiopathology; D015153:Blotting, Western; D002199:Capillary Permeability / Q000502:physiology; D004195:Disease Models, Animal; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D007511:Ischemia / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D017628:Microglia / Q000473:pathology / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000503:physiopathology*; D014158:Transcription, Genetic / Q000502:physiology
keywords: Acute kidney injury; Brain inflammation; Hippocampal transcriptional dysregulation