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This study aimed to investigate the effect of cannabidiol (CBD) on improving depressive\u2010like behaviors and BBB impairment, as well as its underlying mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Depressive\u2010like behaviors in mice were assessed via exploratory and despair\u2010like 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Mice with depressive\u2010like phenotypes showed reduced exploratory behavior and increased despair\u2010like 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\u2013associated secondary neuroinflammation, thereby alleviating depressive\u2010like behaviors in mice with depressive\u2010like phenotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Experimental results show that CBD treatment can improve BBB dysfunction in depression and further indicates that targeted inhibition of memory astrocytes\u2010mediated neuroinflammation may promote the treatment of depression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71168","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:01:34Z","timestamp":1789563694000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cannabidiol Ameliorates Blood\u2013Brain Barrier Dysfunction and 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