Genomic response of the rat brain to global ischemia and reperfusion.
To identify genes that are involved in ischemia response of the brain, we have evaluated changes of gene expression in rat cerebrum after 15 min complete global ischemia, followed by reperfusion for 1 h, 6 h or 24 h. The expression profiles of approximately 30,000 transcripts from three subjects in each group (including sham-operated controls) were monitored employing oligonucleotide microarrays. About 20,000 transcripts were detectable in rat brains. The levels of 576 transcripts (approximately 2.9%) were significantly altered in response to experimental ischemia. 419 transcripts were up- and 157 downregulated; 39 transcripts changed after 1 h reperfusion, 174 after 6 h and 462 after 24 h. Results from quantitative real-time reverse transcription PCR of 18 selected genes showed excellent agreement with the microarray data. There is surprisingly little overlap between gene regulation patterns at different reperfusion times (only seven genes displayed significant changes in transcript levels at all reperfusion times. Several genes that were previously unknown to be involved in ischemia-response have been identified. Analyses of gene ontology patterns and the most strongly regulated transcripts showed that the immediate response to an ischemia/reperfusion is mediated by the induction of specific transcription factors and stress genes. Delayed gene expression response is characterised by inflammation and immune-related genes. These results support the hypothesis that the brain's response to ischemia is an active, specific and coordinated process.
Büttner
Fabian
F
Institute of Zoology, University of Mainz, Müllerweg 6, D-55099 Mainz, Germany.
Cordes
Christian
C
Gerlach
Frank
F
Heimann
Axel
A
Alessandri
Beat
B
Luxemburger
Ulrich
U
Türeci
Ozlem
O
Hankeln
Thomas
T
Kempski
Oliver
O
Burmester
Thorsten
T
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012313:RNA