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Erythropoietin Prevents Blood Brain Barrier Damage Induced by Focal Cerebral Ischemia in Mice

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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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Acknowledgment

This work was supported by NIH grants NS 37372, NS 045155, and NS 045810. The work was also supported by NIH C06 RR015455 from the Extramural Research Facilities Program of the National Center for Research Resources.

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  1. Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 165 Ashley Ave., Charleston, SC, 29425, USA

    Ying Li, Zhong-Yang Lu, Molly Ogle & Ling Wei

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  1. Ying Li
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  2. Zhong-Yang Lu
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  3. Molly Ogle
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  4. Ling Wei
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Correspondence to Ling Wei.

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Li, Y., Lu, ZY., Ogle, M. et al. Erythropoietin Prevents Blood Brain Barrier Damage Induced by Focal Cerebral Ischemia in Mice. Neurochem Res 32, 2132–2141 (2007). https://doi.org/10.1007/s11064-007-9387-9

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  • DOI: https://doi.org/10.1007/s11064-007-9387-9

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