Erythropoietin Prevents Blood Brain Barrier Damage Induced by Focal Cerebral Ischemia in Mice |
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Authors: | Ying Li Zhong-Yang Lu Molly Ogle Ling Wei |
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Institution: | (1) Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 165 Ashley Ave., Charleston, SC 29425, USA |
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Abstract: | Recombinant human erythropoietin (rhEPO), a neurovascular protective agent, therapeutically supports angiogenesis after stroke
by enhancing endogenous up-regulation of vascular endothelial growth factor (VEGF). Increased VEGF expression has been characterized
to negatively impact the integrity of the blood brain barrier (BBB), causing brain edema and secondary injury. The present
study investigated the rhEPO-induced BBB protection after stroke and how it might be achieved by affecting VEGF pathway. rhEPO
treatment (5,000 U/kg, i.p., 30 min before stroke and once a day for three days after stroke) reduced Evans blue leakage and
brain edema after ischemia. The expression of the BBB integrity markers, occludin, α-catenin and β-catenin, in the brain was
preserved in animals received rhEPO. rhEPO up-regulated VEGF expression; however, the expression of VEGF receptor-2 (fetal
liver kinase receptor, Flk-1) was significantly reduced in rhEPO-treated animals three days after stroke. We propose that,
disregarding increased VEGF levels, rhEPO protects against ischemia-induced BBB damage at least partly by down-regulating
Flk-1 expression and the response to VEGF signaling in the acute phase after stroke. |
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Keywords: | Stroke Edema rhEPO BBB VEGF Flk-1 Endothelial cells Angiogenesis |
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