U0126 attenuates cerebral vasoconstriction and improves long-term neurologic outcome after stroke in female rats.
Ahnstedt, Hilda LU ; Mostajeran, Maryam LU ; Blixt, Frank LU ; Warfvinge, Karin LU
; Ansar, Saema
LU
; Krause, Diana N
and Edvinsson, Lars
LU
(2015)
In Journal of Cerebral Blood Flow and Metabolism
35(3).
p.454-460
- Abstract
- Sex differences are well known in cerebral ischemia and may impact the effect of stroke treatments. In male rats, the MEK1/2 inhibitor U0126 reduces ischemia-induced endothelin type B (ETB) receptor upregulation, infarct size and improves acute neurologic function after experimental stroke. However, responses to this treatment in females and long-term effects on outcome are not known. Initial experiments used in vitro organ culture of cerebral arteries, confirming ERK1/2 activation and increased ETB receptor-mediated vasoconstriction in female cerebral arteries. Transient middle cerebral artery occlusion (tMCAO, 120 minutes) was induced in female Wistar rats, with U0126 (30 mg/kg intraperitoneally) or vehicle administered at 0 and 24 hours... (More)
- Sex differences are well known in cerebral ischemia and may impact the effect of stroke treatments. In male rats, the MEK1/2 inhibitor U0126 reduces ischemia-induced endothelin type B (ETB) receptor upregulation, infarct size and improves acute neurologic function after experimental stroke. However, responses to this treatment in females and long-term effects on outcome are not known. Initial experiments used in vitro organ culture of cerebral arteries, confirming ERK1/2 activation and increased ETB receptor-mediated vasoconstriction in female cerebral arteries. Transient middle cerebral artery occlusion (tMCAO, 120 minutes) was induced in female Wistar rats, with U0126 (30 mg/kg intraperitoneally) or vehicle administered at 0 and 24 hours of reperfusion, or with no treatment. Infarct volumes were determined and neurologic function was assessed by 6-point and 28-point neuroscores. ETB receptor-mediated contraction was studied with myograph and protein expression with immunohistochemistry. In vitro organ culture and tMCAO resulted in vascular ETB receptor upregulation and activation of ERK1/2 that was prevented by U0126. Although no effect on infarct size, U0126 improved the long-term neurologic function after experimental stroke in female rats. In conclusion, early prevention of the ERK1/2 activation and ETB receptor-mediated vasoconstriction in the cerebral vasculature after ischemic stroke in female rats improves the long-term neurologic outcome.Journal of Cerebral Blood Flow & Metabolism advance online publication, 10 December 2014; doi:10.1038/jcbfm.2014.217. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4908697
- author
- Ahnstedt, Hilda
LU
; Mostajeran, Maryam
LU
; Blixt, Frank
LU
; Warfvinge, Karin
LU
; Ansar, Saema
LU
; Krause, Diana N
and Edvinsson, Lars
LU
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Cerebral Blood Flow and Metabolism
- volume
- 35
- issue
- 3
- pages
- 454 - 460
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:25492115
- wos:000350393600014
- pmid:25492115
- scopus:84938527442
- ISSN
- 1559-7016
- DOI
- 10.1038/jcbfm.2014.217
- language
- English
- LU publication?
- yes
- id
- aba6058c-293f-42a0-ab2f-35d8f163e22a (old id 4908697)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/25492115?dopt=Abstract
- date added to LUP
- 2016-04-01 10:03:34
- date last changed
- 2024-01-06 06:40:01
@article{aba6058c-293f-42a0-ab2f-35d8f163e22a,
abstract = {{Sex differences are well known in cerebral ischemia and may impact the effect of stroke treatments. In male rats, the MEK1/2 inhibitor U0126 reduces ischemia-induced endothelin type B (ETB) receptor upregulation, infarct size and improves acute neurologic function after experimental stroke. However, responses to this treatment in females and long-term effects on outcome are not known. Initial experiments used in vitro organ culture of cerebral arteries, confirming ERK1/2 activation and increased ETB receptor-mediated vasoconstriction in female cerebral arteries. Transient middle cerebral artery occlusion (tMCAO, 120 minutes) was induced in female Wistar rats, with U0126 (30 mg/kg intraperitoneally) or vehicle administered at 0 and 24 hours of reperfusion, or with no treatment. Infarct volumes were determined and neurologic function was assessed by 6-point and 28-point neuroscores. ETB receptor-mediated contraction was studied with myograph and protein expression with immunohistochemistry. In vitro organ culture and tMCAO resulted in vascular ETB receptor upregulation and activation of ERK1/2 that was prevented by U0126. Although no effect on infarct size, U0126 improved the long-term neurologic function after experimental stroke in female rats. In conclusion, early prevention of the ERK1/2 activation and ETB receptor-mediated vasoconstriction in the cerebral vasculature after ischemic stroke in female rats improves the long-term neurologic outcome.Journal of Cerebral Blood Flow & Metabolism advance online publication, 10 December 2014; doi:10.1038/jcbfm.2014.217.}},
author = {{Ahnstedt, Hilda and Mostajeran, Maryam and Blixt, Frank and Warfvinge, Karin and Ansar, Saema and Krause, Diana N and Edvinsson, Lars}},
issn = {{1559-7016}},
language = {{eng}},
number = {{3}},
pages = {{454--460}},
publisher = {{Nature Publishing Group}},
series = {{Journal of Cerebral Blood Flow and Metabolism}},
title = {{U0126 attenuates cerebral vasoconstriction and improves long-term neurologic outcome after stroke in female rats.}},
url = {{http://dx.doi.org/10.1038/jcbfm.2014.217}},
doi = {{10.1038/jcbfm.2014.217}},
volume = {{35}},
year = {{2015}},
}