XQ-1H regulates Wnt/GSK3ß/ß-catenin pathway and ameliorates the integrity of blood brain barrier in mice with acute ischemic stroke.
Brain Res Bull
; 164: 269-288, 2020 11.
Article
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| MEDLINE
| ID: mdl-32916221
ABSTRACT
10-O-(N, N-dimethylaminoethyl) ginkgolide B methanesulfonate (XQ-1H), a novel analog of ginkgolide B, has been preliminarily recognized to show bioactivities against ischemia-induced injury. However, the underlying mechanism still remains to be fully elucidated. The aim of this study was to investigate the effect of XQ-1H against cerebral ischemia/reperfusion injury (CIRI) from the perspective of blood brain barrier (BBB) protection, and explore whether the underlying mechanism is associated with Wnt/GSK3ß/ß-catenin signaling pathway activation. The therapeutic effects of XQ-1H were evaluated in mice subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) and in immortalized mouse cerebral endothelial cells (bEnd.3) challenged by oxygen and glucose deprivation/reoxygenation (OGD/R). Results showed that treatment with XQ-1H improved neurological behavior, reduced brain infarction volume, diminished edema, and attenuated the disruption of BBB in vivo. In vitro, XQ-1H increased cell viability and maintained the barrier function of bEnd.3 monolayer after OGD/R. Moreover, the protection of XQ-1H was accompanied with activation of Wnt/GSK3ß/ß-catenin pathway and upregulation of tight junction proteins. Notably, the protection of XQ-1H was abolished by Wnt/GSK3ß/ß-catenin inhibitor XAV939 or ß-catenin siRNA, indicating XQ-1H exerted protection in a Wnt/GSK3ß/ß-catenin dependent profile. In summary, XQ-1H attenuated brain injury and maintained BBB integrity after CIRI, and the possible underlying mechanism may be related to the activation of Wnt/GSK3ß/ß-catenin pathway and upregulation of tight junction proteins.
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Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Barrera Hematoencefálica
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Fármacos Neuroprotectores
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Ginkgólidos
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Vía de Señalización Wnt
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Accidente Cerebrovascular Isquémico
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Lactonas
Límite:
Animals
Idioma:
En
Revista:
Brain Res Bull
Año:
2020
Tipo del documento:
Article