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Tissue plasminogen activator enhances the hypoxia/reoxygenation-induced impairment of the blood-brain barrier in a primary culture of rat brain endothelial cells.


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Title: Tissue plasminogen activator enhances the hypoxia/reoxygenation-induced impairment of the blood-brain barrier in a primary culture of rat brain endothelial cells.
Authors: Hiu, Takeshi / Nakagawa, Sinsuke / Hayashi, Kentaro / Kitagawa, Naoki / Tsutsumi, Keisuke / Kawakubo, Junichi / Honda, Masaru / Suyama, Kazuhiko / Nagata, Izumi / Niwa, Masami
Issue Date: Dec-2008
Publisher: Springer Netherlands
Citation: Cellular and molecular neurobiology, 28(8), pp.1139-1146; 2008
Abstract: Hemorrhagic transformation is a major complication associated with tissue plasminogen activator (tPA) therapy for ischemic stroke. We studied the effect of tPA on the blood-brain barrier (BBB) function with our in vitro monolayer model generated using rat brain microvascular endothelial cells subjected either to normoxia or to hypoxia/reoxygenation (H/R) with or without the administration of tPA. The barrier function was evaluated by the transendothelial electrical resistance (TEER), the permeability of sodium fluorescein and Evans' blue-albumin (EBA), and the uptake of lucifer yellow (LY). The permeability of sodium fluorescein and EBA was used as an index of paracellular and transcellular transport, respectively. The administration of tPA increased the permeability of EBA and the uptake of LY under normoxia. It enhanced the increase in the permeability of both sodium fluorescein and EBA, the decrease in the TEER, and the disruption in the expression of ZO-1 under H/R conditions. Administration of tPA could cause an increase in the transcellular transport under normoxia, and both the transcellular and paracellular transport of the BBB under H/R conditions in vitro. Even in humans, tPA may lead to an opening of the BBB under non-ischemic conditions and have an additional effect on the ischemia-induced BBB disruption.
Description: The original publication is available at www.springerlink.com
Keywords: Blood-brain barrier / Brain capillary endothelial cells (rat) / Hypoxia/reoxygenation (in vitro) / Tight junction / Tissue plasminogen activator / Transendothelial electrical resistance / Transendothelial permeability
URI: http://hdl.handle.net/10069/23082
ISSN: 02724340
DOI: 10.1007/s10571-008-9294-x
PubMed ID: 18629628
Rights: © Springer Science+Business Media, LLC 2008
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/23082

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