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Cerebral ischemia induces transcription of inflammatory and extracellular-matrix-related genes in rat cerebral arteries.

Vikman, Petter LU ; Ansar, Saema; Henriksson, Marie LU ; Stenman, Emelie LU and Edvinsson, Lars LU (2007) In Experimental Brain Research 183(4). p.499-510
Abstract
Cerebral ischemia results in a local inflammatory response that contributes to the size of the lesion, however, the involvement of the cerebral vasculature is unknown. We hypothesise that the expression of inflammatory genes (Il6, iNOS, cxcl2, TNF-α and Il-1β) and extracellular-matrix-related genes (MMP9, MMP13) is induced in cerebral arteries following cerebral ischemia via activation of mitogen activated kinases (MAPKs). This hypothesis was tested in vivo by experimental subarachnoid haemorrhage (SAH) and temporal middle cerebral artery occlusion (MCAO), and by organ culture of isolated cerebral arteries with quantitative real time PCR (mRNA expression) and immunohistochemistry (localization of protein expression). The gene promoters... (More)
Cerebral ischemia results in a local inflammatory response that contributes to the size of the lesion, however, the involvement of the cerebral vasculature is unknown. We hypothesise that the expression of inflammatory genes (Il6, iNOS, cxcl2, TNF-α and Il-1β) and extracellular-matrix-related genes (MMP9, MMP13) is induced in cerebral arteries following cerebral ischemia via activation of mitogen activated kinases (MAPKs). This hypothesis was tested in vivo by experimental subarachnoid haemorrhage (SAH) and temporal middle cerebral artery occlusion (MCAO), and by organ culture of isolated cerebral arteries with quantitative real time PCR (mRNA expression) and immunohistochemistry (localization of protein expression). The gene promoters were investigated in silica with computer analysis. The mRNA analysis revealed that the ischemic models, SAH and MCAO, as well as organ culture of isolated cerebral arteries resulted in transcriptional upregulation of the abovementioned genes. The protein expression involved phosphorylation of three different MAPKs signalling pathways (p38, ERK 1/2 and SAPK/JNK) and the downstream transcription factors (ATF-2, Elk-1, c-Jun) shown by immunohistochemistry and quantified by image analysis. All three models revealed the same pattern of activation in the cerebrovascular smooth muscle cells. The in silica analysis demonstrated binding sites for said transcription factors. The results suggest that cerebral ischemia and organ culture induce activation of p38, ERK 1/2 and SAPK/JNK in cerebral arteries which in turn activate the transcription factors ATF-2, Elk-1 and c-Jun and the expression of inflammatory and extracellular-matrix-related genes in the wall of cerebral arteries. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Extra cellular matrix, Stroke, Inflammation, Cerebral blood flow, Cerebral infarct, Mitogen activated kinases
in
Experimental Brain Research
volume
183
issue
4
pages
499 - 510
publisher
Springer
external identifiers
  • wos:000250465200008
  • scopus:35648950527
ISSN
0014-4819
DOI
10.1007/s00221-007-1062-5
language
English
LU publication?
yes
id
e0ee72dd-cfb4-4b98-b75f-85b278406aa1 (old id 607905)
date added to LUP
2008-08-19 16:10:31
date last changed
2017-06-11 03:48:57
@article{e0ee72dd-cfb4-4b98-b75f-85b278406aa1,
  abstract     = {Cerebral ischemia results in a local inflammatory response that contributes to the size of the lesion, however, the involvement of the cerebral vasculature is unknown. We hypothesise that the expression of inflammatory genes (Il6, iNOS, cxcl2, TNF-α and Il-1β) and extracellular-matrix-related genes (MMP9, MMP13) is induced in cerebral arteries following cerebral ischemia via activation of mitogen activated kinases (MAPKs). This hypothesis was tested in vivo by experimental subarachnoid haemorrhage (SAH) and temporal middle cerebral artery occlusion (MCAO), and by organ culture of isolated cerebral arteries with quantitative real time PCR (mRNA expression) and immunohistochemistry (localization of protein expression). The gene promoters were investigated in silica with computer analysis. The mRNA analysis revealed that the ischemic models, SAH and MCAO, as well as organ culture of isolated cerebral arteries resulted in transcriptional upregulation of the abovementioned genes. The protein expression involved phosphorylation of three different MAPKs signalling pathways (p38, ERK 1/2 and SAPK/JNK) and the downstream transcription factors (ATF-2, Elk-1, c-Jun) shown by immunohistochemistry and quantified by image analysis. All three models revealed the same pattern of activation in the cerebrovascular smooth muscle cells. The in silica analysis demonstrated binding sites for said transcription factors. The results suggest that cerebral ischemia and organ culture induce activation of p38, ERK 1/2 and SAPK/JNK in cerebral arteries which in turn activate the transcription factors ATF-2, Elk-1 and c-Jun and the expression of inflammatory and extracellular-matrix-related genes in the wall of cerebral arteries.},
  author       = {Vikman, Petter and Ansar, Saema and Henriksson, Marie and Stenman, Emelie and Edvinsson, Lars},
  issn         = {0014-4819},
  keyword      = {Extra cellular matrix,Stroke,Inflammation,Cerebral blood flow,Cerebral infarct,Mitogen activated kinases},
  language     = {eng},
  number       = {4},
  pages        = {499--510},
  publisher    = {Springer},
  series       = {Experimental Brain Research},
  title        = {Cerebral ischemia induces transcription of inflammatory and extracellular-matrix-related genes in rat cerebral arteries.},
  url          = {http://dx.doi.org/10.1007/s00221-007-1062-5},
  volume       = {183},
  year         = {2007},
}