Effect of hypoxic preconditioning on brain genomic response before and following ischemia in the adult mouse: identification of potential neuroprotective candidates for stroke.
The aim of the present study is to better understand oxygen-sensitive adaptative pathways underlying the hypoxic preconditioning-induced protection of the brain against ischemia. Using oligonucleotide microarrays, we examined the brain genomic response of adult mice following hypoxia preconditioning (8% O2 for 1 or 6 h of hypoxia with reoxygenation 12, 18, 24 h or 72 h) and ischemia (6 h), preceeded (tolerant state) or not, by preconditioning. Real-time PCR was used to validate the results. Most gene expression increases occurred during hypoxia, including those of HIF-1-dependent genes (RTP801, AM, VEGF, p21, GLUT-1), early response genes (IER3) and transcriptional factors (ATF3, C/EBPdelta). A second wave of changes occurred 24 h after reoxygenation (S100A5, TH, Calretinin, PBX3). A third one occurred during ischemia itself, revealing that hypoxic preconditioning modifies the brain genomic response to ischemia. In addition, we show that some identical genes are overexpressed by hypoxia in both neonatal and adult brains (VEGF, EPO, GLUT-1, AM, MTs, C/EBPdelta).
Tang
Yang
Y
The M.I.N.D. Institute and Department of Neurology, University of California at Davis, Davis, CA 95616, USA.
Pacary
Emilie
E
Fréret
Thomas
T
Divoux
Didier
D
Petit
Edwige
E
Schumann-Bard
Pascale
P
Bernaudin
Myriam
M
D000367:Age Factors; D000818:Animals; D001923:Brain Chemistry / Q000235:genetics; D020869:Gene Expression Profiling; D023281:Genomics; D002534:Hypoxia, Brain / Q000235:genetics* / Q000503:physiopathology; D019194:Ischemic Preconditioning; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D020521:Stroke / Q000235:genetics* / Q000503:physiopathology; D015854:Up-Regulation / Q000235:genetics