title: Comprehensive regional and temporal gene expression profiling of the rat brain during the first 24 h after experimental stroke identifies dynamic ischemia-induced gene expression patterns, and reveals a biphasic activation of genes in surviving tissue.
abstract: In order to identify biological processes relevant for cell death and survival in the brain following stroke, the postischemic brain transcriptome was studied by a large-scale cDNA array analysis of three peri-infarct brain regions at eight time points during the first 24 h of reperfusion following middle cerebral artery occlusion in the rat. K-means cluster analysis revealed two distinct biphasic gene expression patterns that contained 44 genes (including 18 immediate early genes), involved in cell signaling and plasticity (i.e. MAP2K7, Sprouty2, Irs-2, Homer1, GPRC5B, Grasp). The first gene induction phase occurred at 0-3 h of reperfusion, and the second at 9-15 h, and was validated by in situ hybridization. Four gene clusters displayed a progressive increase in expression over time and included 50 genes linked to cell motility, lipid synthesis and trafficking (i.e. ApoD, NPC1, G3P-dehydrogenase1, and Choline kinase) or cell death-regulating genes such as mitochondrial CLIC. We conclude that a biphasic transcriptional up-regulation of the brain-derived neurotrophic factor (BDNF)-G-protein coupled receptor (GPCR)-mitogen-activated protein (MAP) kinase signaling pathways occurs in surviving tissue, concomitant with a progressive and persistent activation of cell proliferation signifying tissue regeneration, which provide the means for cell survival and postischemic brain plasticity.
authors.affiliation: Laboratory for Experimental Brain Research, Wallenberg Neuroscience Center, University of Lund, Lund, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Rickhag
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Wieloch
authors.forename: Gunilla
authors.initials: G
authors.lastname: Gidö
authors.forename: Eskil
authors.initials: E
authors.lastname: Elmér
authors.forename: Morten
authors.initials: M
authors.lastname: Krogh
authors.forename: Joseph
authors.initials: J
authors.lastname: Murray
authors.forename: Scott
authors.initials: S
authors.lastname: Lohr
authors.forename: Hans
authors.initials: H
authors.lastname: Bitter
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Chin
authors.forename: David
authors.initials: D
authors.lastname: von Schack
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Shamloo
authors.forename: Karoly
authors.initials: K
authors.lastname: Nikolich
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry / Q000235:genetics*; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D017403:In Situ Hybridization; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000473:pathology; D008297:Male; D005810:Multigene Family / Q000235:genetics; D009416:Nerve Regeneration / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000378:metabolism*; D013569:Synapses / Q000502:physiology; D015533:Transcriptional Activation
chemical_list: D018076:DNA, Complementary; D012313:RNA