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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

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@article{ede850ba039f46c3aae3c3146c1570ab,
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",
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 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.",
keywords = "Journal Article",
author = "M Mostajeran and F Wetterling and {W Blixt}, F and L Edvinsson and S Ansar",
note = "{\textcopyright} 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.",
year = "2018",
doi = "10.1111/apha.12985",
language = "English",
volume = "223",
pages = "e12985",
journal = "Acta Physiologica (Online)",
issn = "1748-1716",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "1",

}

RIS

TY - JOUR

T1 - 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

AU - Mostajeran, M

AU - Wetterling, F

AU - W Blixt, F

AU - Edvinsson, L

AU - Ansar, S

N1 - © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1111/apha.12985

DO - 10.1111/apha.12985

M3 - Journal article

C2 - 29055086

VL - 223

SP - e12985

JO - Acta Physiologica (Online)

JF - Acta Physiologica (Online)

SN - 1748-1716

IS - 1

ER -

ID: 53670508