Neural progenitor cell-derived extracellular vesicles enhance blood-brain barrier integrity by NF-kappa B (Nuclear Factor-kappa B)-dependent regulation of ABCB1 (ATP-Binding Cassette Transporter B1) in stroke mice

dc.authorid0000-0001-6494-8923
dc.contributor.authorZhang, Lin
dc.contributor.authorGraf, Irina
dc.contributor.authorKuang, Yaoyun
dc.contributor.authorZheng, Xuan
dc.contributor.authorHaupt, Matteo
dc.contributor.authorMajid, Arshad
dc.contributor.authorKılıç, Ertuğrul
dc.contributor.authorHermann, Dirk M.
dc.contributor.authorPsychogios, Marios-Nikos
dc.contributor.authorWeber, Martin S.
dc.contributor.authorOchs, Jasmin
dc.contributor.authorBaehr, Mathias
dc.contributor.authorDoeppner, Thorsten R.
dc.date.accessioned2021-05-27T13:29:57Z
dc.date.available2021-05-27T13:29:57Z
dc.date.issued2021
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER)
dc.description.abstractObjective: Extracellular vesicles (EVs) derived from neural progenitor cells enhance poststroke neurological recovery, albeit the underlying mechanisms remain elusive. Since previous research described an enhanced poststroke integrity of the blood-brain barrier (BBB) upon systemic transplantation of neural progenitor cells, we examined if neural progenitor cell-derived EVs affect BBB integrity and which cellular mechanisms are involved in the process. Approach and Results: Using in vitro models of primary brain endothelial cell (EC) cultures as well as co-cultures of brain ECs (ECs) and astrocytes exposed to oxygen glucose deprivation, we examined the effects of EVs or vehicle on microvascular integrity. In vitro data were confirmed using a mouse transient middle cerebral artery occlusion model. Cultured ECs displayed increased ABCB1 (ATP-binding cassette transporter B1) levels when exposed to oxygen glucose deprivation, which was reversed by treatment with EVs. The latter was due to an EV-induced inhibition of the NF-kappa B (nuclear factor-kappa B) pathway. Using a BBB co-culture model of ECs and astrocytes exposed to oxygen glucose deprivation, EVs stabilized the BBB and ABCB1 levels without affecting the transcellular electrical resistance of ECs. Likewise, EVs yielded reduced Evans blue extravasation, decreased ABCB1 expression as well as an inhibition of the NF-kappa B pathway, and downstream matrix metalloproteinase 9 (MMP-9) activity in stroke mice. The EV-induced inhibition of the NF-kappa B pathway resulted in a poststroke modulation of immune responses. Conclusions: Our findings suggest that EVs enhance poststroke BBB integrity via ABCB1 and MMP-9 regulation, attenuating inflammatory cell recruitment by inhibition of the NF-kappa B pathway.
dc.description.sponsorshipChina Scholarship Councilen_US
dc.identifier.citationZhang, L., Graf, I., Kuang, Y., Zheng, X., Haupt, M., Majid, A. ... Doeppner, T. R. (2021). Neural progenitor cell-derived extracellular vesicles enhance blood-brain barrier integrity by NF-kappa B (Nuclear Factor-kappa B)-dependent regulation of ABCB1 (ATP-Binding Cassette Transporter B1) in stroke mice. Arteriosclerosis, Thrombosis, and Vascular Biology, 41(3), 1127-1145. https://dx.doi.org/10.1161/ATVBAHA.120.315031
dc.identifier.doi10.1161/ATVBAHA.120.315031
dc.identifier.endpage1145
dc.identifier.issn1079-5642
dc.identifier.issn1524-4636
dc.identifier.issue3
dc.identifier.scopusqualityQ1
dc.identifier.startpage1127
dc.identifier.urihttps://dx.doi.org/10.1161/ATVBAHA.120.315031
dc.identifier.urihttps://hdl.handle.net/20.500.12511/6953
dc.identifier.volume41
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherLippincott Williams & Wilkins
dc.relation.ispartofArteriosclerosis, Thrombosis, and Vascular Biologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/legalcode*
dc.subjectAstrocytes
dc.subjectBlood-Brain Barrier
dc.subjectEndothelial Cells
dc.subjectExtracellular Vesicles
dc.subjectMatrix Metalloproteinase 9
dc.titleNeural progenitor cell-derived extracellular vesicles enhance blood-brain barrier integrity by NF-kappa B (Nuclear Factor-kappa B)-dependent regulation of ABCB1 (ATP-Binding Cassette Transporter B1) in stroke mice
dc.typeArticle

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