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
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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. / Rickhag, Karl Mattias; Wieloch, Tadeusz; Gidö, Gunilla; Elmér, Eskil; Krogh, Morten; Murray, Joseph; Lohr, Scott; Bitter, Hans; Chin, Daniel J; von Schack, David; Shamloo, Mehrdad; Nikolich, Karoly.
In: Journal of Neurochemistry, Vol. 96, No. 1, 01.2006, p. 14-29.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - 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
AU - Rickhag, Karl Mattias
AU - Wieloch, Tadeusz
AU - Gidö, Gunilla
AU - Elmér, Eskil
AU - Krogh, Morten
AU - Murray, Joseph
AU - Lohr, Scott
AU - Bitter, Hans
AU - Chin, Daniel J
AU - von Schack, David
AU - Shamloo, Mehrdad
AU - Nikolich, Karoly
PY - 2006/1
Y1 - 2006/1
N2 - 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.
AB - 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.
KW - Animals
KW - Autoradiography
KW - Brain
KW - Brain Chemistry
KW - Brain Ischemia
KW - Cell Proliferation
KW - Cell Survival
KW - DNA, Complementary
KW - Gene Expression Profiling
KW - Gene Expression Regulation
KW - In Situ Hybridization
KW - Infarction, Middle Cerebral Artery
KW - Male
KW - Multigene Family
KW - Nerve Regeneration
KW - Neuronal Plasticity
KW - Oligonucleotide Array Sequence Analysis
KW - RNA
KW - Rats
KW - Rats, Wistar
KW - Stroke
KW - Synapses
KW - Transcriptional Activation
U2 - 10.1111/j.1471-4159.2005.03508.x
DO - 10.1111/j.1471-4159.2005.03508.x
M3 - Journal article
C2 - 16300643
VL - 96
SP - 14
EP - 29
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 1
ER -
ID: 132931445