Lithium attenuates blood-brain barrier damage and brain edema following intracerebral hemorrhage via an endothelial Wnt/β-catenin signaling-dependent mechanism in mice.
Wnt/β-catenin signaling
blood-brain barrier
intracerebral hemorrhage
lithium
tight junction
Journal
CNS neuroscience & therapeutics
ISSN: 1755-5949
Titre abrégé: CNS Neurosci Ther
Pays: England
ID NLM: 101473265
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
revised:
18
12
2021
received:
28
07
2021
accepted:
22
12
2021
pubmed:
29
3
2022
medline:
6
5
2022
entrez:
28
3
2022
Statut:
ppublish
Résumé
Vasogenic cerebral edema resulting from blood-brain barrier (BBB) damage aggravates the devastating consequences of intracerebral hemorrhage (ICH). Although augmentation of endothelial Wnt/β-catenin signaling substantially alleviates BBB breakdown in animals, no agents based on this mechanism are clinically available. Lithium is a medication used to treat bipolar mood disorders and can upregulate Wnt/β-catenin signaling. We evaluated the protective effect of lithium on the BBB in a mouse model of collagenase IV-induced ICH. Furthermore, we assessed the effect and dependency of lithium on Wnt/β-catenin signaling in mice with endothelial deletion of the Wnt7 coactivator Gpr124. Lithium treatment (3 mmol/kg) significantly decreased the hematoma volume (11.15 ± 3.89 mm Our findings indicate that lithium may serve as a therapeutic candidate for treating BBB breakdown and brain edema following ICH.
Sections du résumé
BACKGROUND
Vasogenic cerebral edema resulting from blood-brain barrier (BBB) damage aggravates the devastating consequences of intracerebral hemorrhage (ICH). Although augmentation of endothelial Wnt/β-catenin signaling substantially alleviates BBB breakdown in animals, no agents based on this mechanism are clinically available. Lithium is a medication used to treat bipolar mood disorders and can upregulate Wnt/β-catenin signaling.
METHODS
We evaluated the protective effect of lithium on the BBB in a mouse model of collagenase IV-induced ICH. Furthermore, we assessed the effect and dependency of lithium on Wnt/β-catenin signaling in mice with endothelial deletion of the Wnt7 coactivator Gpr124.
RESULTS
Lithium treatment (3 mmol/kg) significantly decreased the hematoma volume (11.15 ± 3.89 mm
CONCLUSION
Our findings indicate that lithium may serve as a therapeutic candidate for treating BBB breakdown and brain edema following ICH.
Identifiants
pubmed: 35343071
doi: 10.1111/cns.13832
pmc: PMC9062576
doi:
Substances chimiques
beta Catenin
0
Lithium
9FN79X2M3F
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
862-872Informations de copyright
© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.
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