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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, Mattias LU ; Wieloch, Tadeusz LU ; Gidö, Gunilla LU ; Elmer, Eskil LU orcid ; Krogh, Morten LU ; Murray, J ; Lohr, S ; Bitter, H ; Chin, DJ and von Schack, D , et al. (2006) In Journal of Neurochemistry 96(1). p.14-29
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
G-protein, myelin, ischemia, gene expression profiling, cluster analysis, chaperone
in
Journal of Neurochemistry
volume
96
issue
1
pages
14 - 29
publisher
Wiley-Blackwell
external identifiers
  • wos:000233829900002
  • pmid:16300643
  • scopus:33644834481
ISSN
1471-4159
DOI
10.1111/j.1471-4159.2005.03508.x
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Computational biology and biological physics (000006113), Laboratory for Experimental Brain Research (013041000)
id
83007acb-cd0b-4f3d-8a2c-e1c9253cdc5f (old id 693849)
date added to LUP
2016-04-01 16:59:13
date last changed
2021-09-08 04:23:46
@article{83007acb-cd0b-4f3d-8a2c-e1c9253cdc5f,
  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.},
  author       = {Rickhag, Mattias and Wieloch, Tadeusz and Gidö, Gunilla and Elmer, Eskil and Krogh, Morten and Murray, J and Lohr, S and Bitter, H and Chin, DJ and von Schack, D and Shamloo, M and Nikolich, K},
  issn         = {1471-4159},
  language     = {eng},
  number       = {1},
  pages        = {14--29},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Neurochemistry},
  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},
  url          = {http://dx.doi.org/10.1111/j.1471-4159.2005.03508.x},
  doi          = {10.1111/j.1471-4159.2005.03508.x},
  volume       = {96},
  year         = {2006},
}