Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Mostajeran, M. LU ; Wetterling, F. LU ; Blixt, F. W. LU ; Edvinsson, L. LU and Ansar, S. LU (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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; and
organization
publishing date
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
2021-10-06 03:18:20
@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},
  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},
}