Early MEK1/2 Inhibition after Global Cerebral Ischemia in Rats Reduces Brain Damage and Improves Outcome by Preventing Delayed Vasoconstrictor Receptor Upregulation.
(2014) In PLoS ONE 9(3).- Abstract
- Global cerebral ischemia following cardiac arrest is associated with increased cerebral vasoconstriction and decreased cerebral blood flow, contributing to delayed neuronal cell death and neurological detriments in affected patients. We hypothesize that upregulation of contractile ETB and 5-HT1B receptors, previously demonstrated in cerebral arteries after experimental global ischemia, are a key mechanism behind insufficient perfusion of the post-ischemic brain, proposing blockade of this receptor upregulation as a novel target for prevention of cerebral hypoperfusion and delayed neuronal cell death after global cerebral ischemia. The aim was to characterize the time-course of receptor upregulation and associated neuronal damage after... (More)
- Global cerebral ischemia following cardiac arrest is associated with increased cerebral vasoconstriction and decreased cerebral blood flow, contributing to delayed neuronal cell death and neurological detriments in affected patients. We hypothesize that upregulation of contractile ETB and 5-HT1B receptors, previously demonstrated in cerebral arteries after experimental global ischemia, are a key mechanism behind insufficient perfusion of the post-ischemic brain, proposing blockade of this receptor upregulation as a novel target for prevention of cerebral hypoperfusion and delayed neuronal cell death after global cerebral ischemia. The aim was to characterize the time-course of receptor upregulation and associated neuronal damage after global ischemia and investigate whether treatment with the MEK1/2 inhibitor U0126 can prevent cerebrovascular receptor upregulation and thereby improve functional outcome after global cerebral ischemia. Incomplete global cerebral ischemia was induced in Wistar rats and the time-course of enhanced contractile responses and the effect of U0126 in cerebral arteries were studied by wire myography and the neuronal cell death by TUNEL. The expression of ETB and 5-HT1B receptors was determined by immunofluorescence. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4382995
- author
- Johansson, Sara Ellinor LU ; Larsen, Stine Schmidt ; Povlsen, Gro Klitgaard and Edvinsson, Lars LU
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 9
- issue
- 3
- article number
- e92417
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- pmid:24642693
- wos:000333259900134
- scopus:84898669982
- pmid:24642693
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0092417
- language
- English
- LU publication?
- yes
- id
- ed6d32a2-b86e-41b3-abfe-f037fcc9cf2c (old id 4382995)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24642693?dopt=Abstract
- date added to LUP
- 2016-04-01 14:52:30
- date last changed
- 2024-01-10 09:31:44
@article{ed6d32a2-b86e-41b3-abfe-f037fcc9cf2c,
abstract = {{Global cerebral ischemia following cardiac arrest is associated with increased cerebral vasoconstriction and decreased cerebral blood flow, contributing to delayed neuronal cell death and neurological detriments in affected patients. We hypothesize that upregulation of contractile ETB and 5-HT1B receptors, previously demonstrated in cerebral arteries after experimental global ischemia, are a key mechanism behind insufficient perfusion of the post-ischemic brain, proposing blockade of this receptor upregulation as a novel target for prevention of cerebral hypoperfusion and delayed neuronal cell death after global cerebral ischemia. The aim was to characterize the time-course of receptor upregulation and associated neuronal damage after global ischemia and investigate whether treatment with the MEK1/2 inhibitor U0126 can prevent cerebrovascular receptor upregulation and thereby improve functional outcome after global cerebral ischemia. Incomplete global cerebral ischemia was induced in Wistar rats and the time-course of enhanced contractile responses and the effect of U0126 in cerebral arteries were studied by wire myography and the neuronal cell death by TUNEL. The expression of ETB and 5-HT1B receptors was determined by immunofluorescence.}},
author = {{Johansson, Sara Ellinor and Larsen, Stine Schmidt and Povlsen, Gro Klitgaard and Edvinsson, Lars}},
issn = {{1932-6203}},
language = {{eng}},
number = {{3}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{Early MEK1/2 Inhibition after Global Cerebral Ischemia in Rats Reduces Brain Damage and Improves Outcome by Preventing Delayed Vasoconstrictor Receptor Upregulation.}},
url = {{https://lup.lub.lu.se/search/files/4209702/4645374.pdf}},
doi = {{10.1371/journal.pone.0092417}},
volume = {{9}},
year = {{2014}},
}