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Cannabidiol Ameliorates Blood-Brain Barrier Dysfunction and Inhibits Memory Astrocytes Activation in Mice With Sickness-Like Behaviors.

Created on 16 Sep 2026

Authors

Yue Chen, Hui Ma, Qian Long, Xuan Fang, Xiaotong Li, Wenhui Xiao, Xinzhou Deng, Fuze Du, Yifei Tan, Yan Wang, Xiaoxia Jiang, Bo Gao, Xin Qiao

Published in

CNS neuroscience & therapeutics. Volume 32. Issue 9. Pages e71168.

Abstract

Blood-brain barrier (BBB) dysfunction has been increasingly implicated in the pathophysiology of depression; however, effective therapeutic strategies targeting this pathology remain limited. This study aimed to investigate the effect of cannabidiol (CBD) on improving depressive-like behaviors and BBB impairment, as well as its underlying mechanism.
Depressive-like behaviors in mice were assessed via exploratory and despair-like tests. BBB integrity was evaluated by examining tight junction protein expression in endothelial cells and AQP4 reduction from the perivascular membrane. Astrocyte activation and neuroinflammation were also measured. The therapeutic effects of a single CBD dose were examined.
Mice with depressive-like phenotypes showed reduced exploratory behavior and increased despair-like behavior. In the BBB, the expression of tight junction proteins in endothelial cells was downregulated; in astrocytes, decreased AQP4 expression was observed, abnormal activation was enhanced, and neuroinflammation was elevated. A single dose of CBD alleviated all the above pathological changes. Further studies demonstrated that CBD exerted its effects by inhibiting memory astrocyte-associated secondary neuroinflammation, thereby alleviating depressive-like behaviors in mice with depressive-like phenotypes.
Experimental results show that CBD treatment can improve BBB dysfunction in depression and further indicates that targeted inhibition of memory astrocytes-mediated neuroinflammation may promote the treatment of depression.

PMID:
42747207
Bibliographic data and abstract were imported from PubMed on 16 Sep 2026.

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