Acute mitogen-activated protein kinase 1/2 inhibition improves functional recovery and vascular changes after ischaemic stroke in rat-monitored by 9.4 T magnetic resonance imaging
(2018) In Acta Physiologica 223(1).- Abstract
Aim: The aim was to evaluate the beneficial effect of early mitogen-activated protein kinase (MEK)1/2 inhibition administered at a clinical relevant time-point using the transient middle cerebral artery occlusion model and a dedicated rodent magnetic resonance imaging system (9.4T) to monitor cerebrovascular changes non-invasively for 2 weeks. Method: Transient middle cerebral artery occlusion was induced in male rats for two hours followed by reperfusion. The specific MEK1/2 inhibitor U0126 was administered ip at 6 and 24 hours post-reperfusion. Neurological functions were evaluated by 6- and 28-point tests. 9.4 T magnetic resonance imaging was used to monitor morphological infarct changes at day 2, 8 and 14 after stroke and to... (More)
Aim: The aim was to evaluate the beneficial effect of early mitogen-activated protein kinase (MEK)1/2 inhibition administered at a clinical relevant time-point using the transient middle cerebral artery occlusion model and a dedicated rodent magnetic resonance imaging system (9.4T) to monitor cerebrovascular changes non-invasively for 2 weeks. Method: Transient middle cerebral artery occlusion was induced in male rats for two hours followed by reperfusion. The specific MEK1/2 inhibitor U0126 was administered ip at 6 and 24 hours post-reperfusion. Neurological functions were evaluated by 6- and 28-point tests. 9.4 T magnetic resonance imaging was used to monitor morphological infarct changes at day 2, 8 and 14 after stroke and to evaluate cerebral perfusion at day 14. Immunohistochemistry evaluation of Ki67 was performed 14 days post-stroke. Results: U0126 improved long-term behavioural outcome and significantly reduced infarct size. In addition, cerebral perfusion in U0126-treated animals was improved compared to the vehicle group. Immunohistochemistry showed a significant increase in Ki67+ cells in U0126-treated animals compared to the vehicle group. Conclusion: Early MEK1/2 inhibition improves long-term functional outcome, promotes recovery processes after stroke and most importantly provides a realistic time window for therapy.
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- author
- Mostajeran, M. LU ; Wetterling, F. LU ; Blixt, F. W. LU ; Edvinsson, L. LU and Ansar, S. LU
- organization
- publishing date
- 2018
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Cerebral perfusion, Infarct size, Ischaemic stroke, Magnetic resonance imaging, Neurological function, Recovery processes
- in
- Acta Physiologica
- volume
- 223
- issue
- 1
- article number
- e12985
- publisher
- Wiley-Blackwell
- external identifiers
-
- scopus:85033687904
- pmid:29055086
- ISSN
- 1748-1716
- DOI
- 10.1111/apha.12985
- language
- English
- LU publication?
- yes
- id
- dbd442c2-9b6c-4c1d-b5e2-94ce2b4646a7
- date added to LUP
- 2017-11-24 08:56:02
- date last changed
- 2024-04-14 22:26:21
@article{dbd442c2-9b6c-4c1d-b5e2-94ce2b4646a7,
abstract = {{<p>Aim: The aim was to evaluate the beneficial effect of early mitogen-activated protein kinase (MEK)1/2 inhibition administered at a clinical relevant time-point using the transient middle cerebral artery occlusion model and a dedicated rodent magnetic resonance imaging system (9.4T) to monitor cerebrovascular changes non-invasively for 2 weeks. Method: Transient middle cerebral artery occlusion was induced in male rats for two hours followed by reperfusion. The specific MEK1/2 inhibitor U0126 was administered ip at 6 and 24 hours post-reperfusion. Neurological functions were evaluated by 6- and 28-point tests. 9.4 T magnetic resonance imaging was used to monitor morphological infarct changes at day 2, 8 and 14 after stroke and to evaluate cerebral perfusion at day 14. Immunohistochemistry evaluation of Ki67 was performed 14 days post-stroke. Results: U0126 improved long-term behavioural outcome and significantly reduced infarct size. In addition, cerebral perfusion in U0126-treated animals was improved compared to the vehicle group. Immunohistochemistry showed a significant increase in Ki67<sup>+</sup> cells in U0126-treated animals compared to the vehicle group. Conclusion: Early MEK1/2 inhibition improves long-term functional outcome, promotes recovery processes after stroke and most importantly provides a realistic time window for therapy.</p>}},
author = {{Mostajeran, M. and Wetterling, F. and Blixt, F. W. and Edvinsson, L. and Ansar, S.}},
issn = {{1748-1716}},
keywords = {{Cerebral perfusion; Infarct size; Ischaemic stroke; Magnetic resonance imaging; Neurological function; Recovery processes}},
language = {{eng}},
number = {{1}},
publisher = {{Wiley-Blackwell}},
series = {{Acta Physiologica}},
title = {{Acute mitogen-activated protein kinase 1/2 inhibition improves functional recovery and vascular changes after ischaemic stroke in rat-monitored by 9.4 T magnetic resonance imaging}},
url = {{http://dx.doi.org/10.1111/apha.12985}},
doi = {{10.1111/apha.12985}},
volume = {{223}},
year = {{2018}},
}