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Increased cortical cell loss and prolonged hemodynamic depression after traumatic brain injury in mice lacking the IP receptor for prostacyclin.

Lundblad, Cornelia LU ; Grände, Per-Olof LU and Bentzer, Peter LU (2008) In Journal of Cerebral Blood Flow and Metabolism 28(2). p.367-376
Abstract
Prostacyclin is the major arachidonic acid metabolite of the vascular endothelium and is produced mainly via the cyclooxygenase-2 pathway. By acting on the prostacyclin (IP) receptor on platelets and vascular smooth muscle cells, prostacyclin exerts vasodilatory and antiaggregative/antiadhesive effects. Previous studies have shown that prostacyclin production increases after brain trauma, but the importance of prostacyclin for posttraumatic hemodynamic alterations and neuron survival has not been investigated. This study evaluated if endogenous prostacyclin plays a role in the pathophysiologic process in the brain after brain trauma. This was performed by comparing prostacyclin (IP) receptor-deficient (IP-/-) mice and mice with functional... (More)
Prostacyclin is the major arachidonic acid metabolite of the vascular endothelium and is produced mainly via the cyclooxygenase-2 pathway. By acting on the prostacyclin (IP) receptor on platelets and vascular smooth muscle cells, prostacyclin exerts vasodilatory and antiaggregative/antiadhesive effects. Previous studies have shown that prostacyclin production increases after brain trauma, but the importance of prostacyclin for posttraumatic hemodynamic alterations and neuron survival has not been investigated. This study evaluated if endogenous prostacyclin plays a role in the pathophysiologic process in the brain after brain trauma. This was performed by comparing prostacyclin (IP) receptor-deficient (IP-/-) mice and mice with functional IP receptor (IP+/+) after a controlled cortical injury regarding contusion volume, cerebral blood flow ([14C]iodoantipyrine autoradiography), number of perfused capillaries (fluorescein isothiocyanate-dextran fluorescence technique), the transfer constant (Ki) for [51Cr]EDTA, and brain water content (wet vs dry weight) in the injured and contralateral cortex. Contusion volume was increased in IP-/- mice compared with IP+/+ mice. Three hours after trauma, cortical blood flow was decreased in the injured cortex of both groups and the reduction in blood flow in the cortex of the IP-/- mice persisted from 3 to 24 h, whereas blood flow approached normal values in the IP+/+ mice after 24 h. No differences could be detected between the two genotypes regarding other hemodynamic parameters. We conclude that the prostacyclin IP receptor is beneficial for neuron survival after brain trauma in mice, an effect that may be mediated by improved cortical perfusion. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Cerebral Blood Flow and Metabolism
volume
28
issue
2
pages
367 - 376
publisher
Nature Publishing Group
external identifiers
  • wos:000252662700014
  • scopus:38549173279
ISSN
1559-7016
DOI
10.1038/sj.jcbfm.9600533
language
English
LU publication?
yes
id
4af92d0c-421c-4a67-b78e-1d47ca64a0c8 (old id 606683)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17713464&dopt=Abstract
date added to LUP
2008-08-05 14:08:19
date last changed
2017-10-22 04:08:55
@article{4af92d0c-421c-4a67-b78e-1d47ca64a0c8,
  abstract     = {Prostacyclin is the major arachidonic acid metabolite of the vascular endothelium and is produced mainly via the cyclooxygenase-2 pathway. By acting on the prostacyclin (IP) receptor on platelets and vascular smooth muscle cells, prostacyclin exerts vasodilatory and antiaggregative/antiadhesive effects. Previous studies have shown that prostacyclin production increases after brain trauma, but the importance of prostacyclin for posttraumatic hemodynamic alterations and neuron survival has not been investigated. This study evaluated if endogenous prostacyclin plays a role in the pathophysiologic process in the brain after brain trauma. This was performed by comparing prostacyclin (IP) receptor-deficient (IP-/-) mice and mice with functional IP receptor (IP+/+) after a controlled cortical injury regarding contusion volume, cerebral blood flow ([14C]iodoantipyrine autoradiography), number of perfused capillaries (fluorescein isothiocyanate-dextran fluorescence technique), the transfer constant (Ki) for [51Cr]EDTA, and brain water content (wet vs dry weight) in the injured and contralateral cortex. Contusion volume was increased in IP-/- mice compared with IP+/+ mice. Three hours after trauma, cortical blood flow was decreased in the injured cortex of both groups and the reduction in blood flow in the cortex of the IP-/- mice persisted from 3 to 24 h, whereas blood flow approached normal values in the IP+/+ mice after 24 h. No differences could be detected between the two genotypes regarding other hemodynamic parameters. We conclude that the prostacyclin IP receptor is beneficial for neuron survival after brain trauma in mice, an effect that may be mediated by improved cortical perfusion.},
  author       = {Lundblad, Cornelia and Grände, Per-Olof and Bentzer, Peter},
  issn         = {1559-7016},
  language     = {eng},
  number       = {2},
  pages        = {367--376},
  publisher    = {Nature Publishing Group},
  series       = {Journal of Cerebral Blood Flow and Metabolism},
  title        = {Increased cortical cell loss and prolonged hemodynamic depression after traumatic brain injury in mice lacking the IP receptor for prostacyclin.},
  url          = {http://dx.doi.org/10.1038/sj.jcbfm.9600533},
  volume       = {28},
  year         = {2008},
}