Advanced

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 (2017) In Acta Physiologica2006-01-01+01:002013-01-01+01:00
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
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Cerebral perfusion, Infarct size, Ischaemic stroke, Magnetic resonance imaging, Neurological function, Recovery processes
in
Acta Physiologica2006-01-01+01:002013-01-01+01:00
publisher
Wiley-Blackwell
external identifiers
  • scopus:85033687904
ISSN
1748-1708
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
2018-01-07 12:26:49
@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         = {1748-1708},
  keyword      = {Cerebral perfusion,Infarct size,Ischaemic stroke,Magnetic resonance imaging,Neurological function,Recovery processes},
  language     = {eng},
  month        = {11},
  publisher    = {Wiley-Blackwell},
  series       = {Acta Physiologica2006-01-01+01:002013-01-01+01:00},
  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},
  year         = {2017},
}