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

Karl Mattias Rickhag; Tadeusz Wieloch; Gunilla Gidö; Eskil Elmér; Morten Krogh; Joseph Murray; Scott Lohr; Hans Bitter; Daniel J Chin; David von Schack; Mehrdad Shamloo; Karoly Nikolich

doi:10.1111/j.1471-4159.2005.03508.x

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

Karl Mattias Rickhag, Tadeusz Wieloch, Gunilla Gidö, Eskil Elmér, Morten Krogh, Joseph Murray, Scott Lohr, Hans Bitter, Daniel J Chin, David von Schack, Mehrdad Shamloo, Karoly Nikolich

Neuropharm and Genetics

72 Citations (Scopus)

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.

Original language	English
Journal	Journal of Neurochemistry
Volume	96
Issue number	1
Pages (from-to)	14-29
Number of pages	16
ISSN	0022-3042
DOIs	https://doi.org/10.1111/j.1471-4159.2005.03508.x
Publication status	Published - Jan 2006

Keywords

Animals
Autoradiography
Brain
Brain Chemistry
Brain Ischemia
Cell Proliferation
Cell Survival
DNA, Complementary
Gene Expression Profiling
Gene Expression Regulation
In Situ Hybridization
Infarction, Middle Cerebral Artery
Male
Multigene Family
Nerve Regeneration
Neuronal Plasticity
Oligonucleotide Array Sequence Analysis
RNA
Rats
Rats, Wistar
Stroke
Synapses
Transcriptional Activation

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Rickhag, K. M., Wieloch, T., Gidö, G., Elmér, E., Krogh, M., Murray, J., Lohr, S., Bitter, H., Chin, D. J., von Schack, D., Shamloo, M., & Nikolich, K. (2006). 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. Journal of Neurochemistry, 96(1), 14-29. https://doi.org/10.1111/j.1471-4159.2005.03508.x

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 et al.

In: Journal of Neurochemistry, Vol. 96, No. 1, 01.2006, p. 14-29.

Research output: Contribution to journal › Journal article › Research › peer-review

Rickhag, KM, Wieloch, T, Gidö, G, Elmér, E, Krogh, M, Murray, J, Lohr, S, Bitter, H, Chin, DJ, von Schack, D, Shamloo, M & Nikolich, K 2006, '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', Journal of Neurochemistry, vol. 96, no. 1, pp. 14-29. https://doi.org/10.1111/j.1471-4159.2005.03508.x

Rickhag KM, Wieloch T, Gidö G, Elmér E, Krogh M, Murray J et al. 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. Journal of Neurochemistry. 2006 Jan;96(1):14-29. doi: 10.1111/j.1471-4159.2005.03508.x

Rickhag, Karl Mattias ; Wieloch, Tadeusz ; Gidö, Gunilla et al. / 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. In: Journal of Neurochemistry. 2006 ; Vol. 96, No. 1. pp. 14-29.

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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.",

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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

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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.

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KW - Autoradiography

KW - Brain

KW - Brain Chemistry

KW - Brain Ischemia

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KW - Cell Survival

KW - DNA, Complementary

KW - Gene Expression Profiling

KW - Gene Expression Regulation

KW - In Situ Hybridization

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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

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SN - 0022-3042

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EP - 29

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

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