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Late cerebral ischaemia after subarachnoid haemorrhage: Is cerebrovascular receptor upregulation the mechanism behind?

Edvinsson, Lars LU and Povlsen, Gro Klitgaard (2011) In Acta Physiologica 203(1). p.209-224
Abstract
Late cerebral ischaemia after subarachnoid haemorrhage (SAH) carries high morbidity and mortality because of reduced cerebral blood flow (CBF) and subsequent cerebral ischaemia. This is associated with upregulation of contractile receptors in cerebral artery smooth muscles via the activation of intracellular signalling. In addition, delayed cerebral ischaemia after SAH is associated with inflammation and disruption of the blood-brain barrier (BBB). This article reviews recent evidence concerning the roles of vasoconstrictor receptor upregulation, inflammation and BBB breakdown in delayed cerebral ischaemia after SAH. In addition, recent studies investigating the role of various intracellular signalling pathways in these processes and the... (More)
Late cerebral ischaemia after subarachnoid haemorrhage (SAH) carries high morbidity and mortality because of reduced cerebral blood flow (CBF) and subsequent cerebral ischaemia. This is associated with upregulation of contractile receptors in cerebral artery smooth muscles via the activation of intracellular signalling. In addition, delayed cerebral ischaemia after SAH is associated with inflammation and disruption of the blood-brain barrier (BBB). This article reviews recent evidence concerning the roles of vasoconstrictor receptor upregulation, inflammation and BBB breakdown in delayed cerebral ischaemia after SAH. In addition, recent studies investigating the role of various intracellular signalling pathways in these processes and the possibilities of targeting signalling components in SAH treatment are discussed. Studies using a rat SAH model have demonstrated that cerebral arteries increase their sensitivity to endogenous agonists such as ET-1 and 5-HT by increasing their smooth muscle expression of receptors for these after SAH. This is associated with reduced CBF and neurological deficits. A number of signal transduction components mediating this receptor upregulation have been identified, including the MEK-ERK1/2 pathway. Inhibition of MEK-ERK1/2 signalling has been shown to prevent cerebrovascular receptor upregulation and normalize CBF and neurological function after SAH in rats. At the same time, in rat SAH, certain cytokines and BBB-regulating proteins are upregulated in cerebral artery smooth muscles and treatment with MEK-ERK1/2 inhibitors prevents the induction of these proteins. Thus, inhibitors of MEK-ERK1/2 signalling exert multimodal beneficial effects in SAH. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
blood-brain barrier, endothelin, inflammation, signal transduction, subarachnoid haemorrhage, vasoconstrictor receptors
in
Acta Physiologica
volume
203
issue
1
pages
209 - 224
publisher
Wiley-Blackwell
external identifiers
  • wos:000293921400019
  • scopus:80051672374
  • pmid:21087418
ISSN
1748-1708
DOI
10.1111/j.1748-1716.2010.02227.x
language
English
LU publication?
yes
id
163bab57-cbdc-4c23-a07f-0f17eb1be49a (old id 2162268)
date added to LUP
2011-10-03 08:40:44
date last changed
2017-11-19 03:02:54
@article{163bab57-cbdc-4c23-a07f-0f17eb1be49a,
  abstract     = {Late cerebral ischaemia after subarachnoid haemorrhage (SAH) carries high morbidity and mortality because of reduced cerebral blood flow (CBF) and subsequent cerebral ischaemia. This is associated with upregulation of contractile receptors in cerebral artery smooth muscles via the activation of intracellular signalling. In addition, delayed cerebral ischaemia after SAH is associated with inflammation and disruption of the blood-brain barrier (BBB). This article reviews recent evidence concerning the roles of vasoconstrictor receptor upregulation, inflammation and BBB breakdown in delayed cerebral ischaemia after SAH. In addition, recent studies investigating the role of various intracellular signalling pathways in these processes and the possibilities of targeting signalling components in SAH treatment are discussed. Studies using a rat SAH model have demonstrated that cerebral arteries increase their sensitivity to endogenous agonists such as ET-1 and 5-HT by increasing their smooth muscle expression of receptors for these after SAH. This is associated with reduced CBF and neurological deficits. A number of signal transduction components mediating this receptor upregulation have been identified, including the MEK-ERK1/2 pathway. Inhibition of MEK-ERK1/2 signalling has been shown to prevent cerebrovascular receptor upregulation and normalize CBF and neurological function after SAH in rats. At the same time, in rat SAH, certain cytokines and BBB-regulating proteins are upregulated in cerebral artery smooth muscles and treatment with MEK-ERK1/2 inhibitors prevents the induction of these proteins. Thus, inhibitors of MEK-ERK1/2 signalling exert multimodal beneficial effects in SAH.},
  author       = {Edvinsson, Lars and Povlsen, Gro Klitgaard},
  issn         = {1748-1708},
  keyword      = {blood-brain barrier,endothelin,inflammation,signal transduction,subarachnoid haemorrhage,vasoconstrictor receptors},
  language     = {eng},
  number       = {1},
  pages        = {209--224},
  publisher    = {Wiley-Blackwell},
  series       = {Acta Physiologica},
  title        = {Late cerebral ischaemia after subarachnoid haemorrhage: Is cerebrovascular receptor upregulation the mechanism behind?},
  url          = {http://dx.doi.org/10.1111/j.1748-1716.2010.02227.x},
  volume       = {203},
  year         = {2011},
}