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Titel: Astrocytic p75NTR expression provoked by ischemic stroke exacerbates the blood-brain barrier disruption
VerfasserIn: Qin, Xiaoying
Wang, Jianing
Chen, Shujian
Liu, Gang
Wu, Chaoran
Lv, Qunyu
He, Xinran
Bai, Xianshu
Huang, Wenhui UdsID
Liao, Hong
Sprache: Englisch
In:
Titel: Glia
Bandnummer: 70
Heft: 5
Seiten: 892–912
Verlag/Plattform: Wiley
Erscheinungsjahr: 2022
Freie Schlagwörter: astrocyte
blood–brain barrier
ischemic stroke
p75NTR
tight junction proteins
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: The disruption of the blood–brain barrier (BBB) plays a critical role in the pathology of ischemic stroke. p75 neurotrophin receptor (p75NTR) contributes to the disruption of the blood-retinal barrier in retinal ischemia. However, whether p75NTR influences the BBB permeability after acute cerebral ischemia remains unknown. The present study investigated the role and underlying mechanism of p75NTR on BBB integrity in an ischemic stroke mouse model, middle cerebral artery occlusion (MCAO). After 24 h of MCAO, astrocytes and endothelial cells in the infarct-affected brain area up-regulated p75NTR. Genetic p75NTR knockdown (p75NTR+/ ) or pharmacological inhibition of p75NTR using LM11A-31, a selective inhibitor of p75NTR, both attenuated brain damage and BBB leakage in MCAO mice. Astrocyte-specific conditional knockdown of p75NTR mediated with an adeno-associated virus significantly ameliorated BBB disruption and brain tissue damage, as well as the neurological functions after stroke. Further molecular biological examinations indicated that astrocytic p75NTR activated NF-κB and HIF-1α signals, which upregulated the expression of MMP-9 and vascular endothelial growth factor (VEGF), subsequently leading to tight junction degradation after ischemia. As a result, increased leukocyte infiltration and microglia activation exacerbated brain injury after stroke. Overall, our results provide novel insight into the role of astrocytic p75NTR in BBB disruption after acute cerebral ischemia. The p75NTR may therefore be a potential therapeutic target for the treatment of ischemic stroke.
DOI der Erstveröffentlichung: 10.1002/glia.24146
URL der Erstveröffentlichung: https://onlinelibrary.wiley.com/doi/10.1002/glia.24146
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-372218
hdl:20.500.11880/33749
http://dx.doi.org/10.22028/D291-37221
ISSN: 1098-1136
0894-1491
Datum des Eintrags: 15-Sep-2022
Bezeichnung des in Beziehung stehenden Objekts: Supporting Information
In Beziehung stehendes Objekt: https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fglia.24146&file=glia24146-sup-0001-Figures.docx
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Physiologie
Professur: M - Prof. Dr. Frank Kirchhoff
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes



Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons Creative Commons