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

作者：Mostajeran M.; Wetterling F.; Blixt F. W.; Edvinsson L.; Ansar S.^*

来源：Acta Physiologica, 2018, 223(1): UNSP e12985.

DOI：10.1111/apha.12985

• cerebral perfusion
• infarct size
• ischaemic stroke
• magnetic resonance imaging
• neurological function
• recovery processes

AimThe 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 2weeks.
MethodTransient 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 24hours 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 14days post-stroke.
ResultsU0126 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.
ConclusionEarly MEK1/2 inhibition improves long-term functional outcome, promotes recovery processes after stroke and most importantly provides a realistic time window for therapy.

• 出版日期2018-5