Erythropoietin prevents blood brain barrier damage induced by focal cerebral ischemia in mice.

Neurochem Res 2007 Dec 12;32(12):2132-41. Epub 2007 Jun 12.

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

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, alpha-catenin and beta-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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http://dx.doi.org/10.1007/s11064-007-9387-9DOI Listing
December 2007
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References

(Supplied by CrossRef)

BT Hawkins et al.
Pharmacol Rev 2005

P Ballabh et al.
Neurobiol Dis 2004

E Dejana et al.
Faseb J 1995

EA Neuwelt et al.
Neurosurgery 2004

S Fischer et al.
Am J Physiol 1999

S Fischer et al.
Microvasc Res 2002

W Wang et al.
Am J Physiol Heart Circ Physiol 2001

OZ Chi et al.
Exp Neurol 2007

S Genc et al.
Restorat Neurol Neurosci 2004

L Wang et al.
Stroke; a J Cerebral Circul 2004

S Bartesaghi et al.
Neurotoxicology 2005

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