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Acute mitogen activated protein kinase 1/2 inhibition improves functional recovery and vascular changes after ischemic stroke in rat‐ monitored by 9.4 T Magnetic Resonance Imaging

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Acta Physiologica

Published online on


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 two 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 i.p 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 behavioral 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 of 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. This article is protected by copyright. All rights reserved.