title: Genome-wide gene expression analysis for induced ischemic tolerance and delayed neuronal death following transient global ischemia in rats.
abstract: Genome-wide gene expression analysis of the hippocampal CA1 region was conducted in a rat global ischemia model for delayed neuronal death and induced ischemic tolerance using an oligonucleotide-based DNA microarray containing 8,799 probes. The results showed that expression levels of 246 transcripts were increased and 213 were decreased following ischemia, corresponding to 5.1% of the represented probe sets. These changes were divided into seven expression clusters using hierarchical cluster analysis, each with distinct conditions and time-specific patterns. Ischemic tolerance was associated with transient up-regulation of transcription factors (c-Fos, JunB Egr-1, -2, -4, NGFI-B), Hsp70 and MAP kinase cascade-related genes (MKP-1), which are implicated cell survival. Delayed neuronal death exhibited complex long-lasting changes of expression, such as up-regulation of proapoptotic genes (GADD153, Smad2, Dral, Caspase-2 and -3) and down-regulation of genes implicated in survival signaling (MKK2, and PI4 kinase, DAG/PKC signaling pathways), suggesting an imbalance between death and survival signals. Our study provides a differential gene expression profile between delayed neuronal death and induced ischemic tolerance in a genome-wide analysis, and contributes to further understanding of the complex molecular pathophysiology in cerebral ischemia.
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, University of Tokyo, Japan. kawahara-tky@umin.ac.jp
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Kawahara
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Akitake
authors.initials: A
authors.lastname: Mukasa
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Furuya
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Shimizu
authors.forename: Takao
authors.initials: T
authors.lastname: Hamakubo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Takaaki
authors.initials: T
authors.lastname: Kirino
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D016923:Cell Death; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016678:Genome; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D017403:In Situ Hybridization; D008297:Male; D009474:Neurons / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D012333:RNA, Messenger