{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T14:14:00Z","timestamp":1779804840398,"version":"3.53.1"},"reference-count":60,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Sleep disturbances are a potential risk factor for stroke. Our clinical cohort shows that insomnia is associated with a higher 90\u2010day stroke recurrence rate, prompting an investigation into the underlying mechanisms, particularly the role of the gut microbiota.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We utilized a rat MCAO model of sleep deprivation (SD) combined with antibiotic (ABX)\u2010induced gut dysbiosis. Neurological deficits were assessed through behavioral tests, and cerebral infarct volume was measured using TTC staining. Structural changes in brain and intestinal tissues were observed by H&amp;E staining, while the expression of blood\u2013brain barrier (BBB)\u2010related proteins was detected by immunofluorescence and Western blot. Gut microbial composition was analyzed by 16S rRNA sequencing, and metabolomic analysis was performed using an untargeted LC\u2013MS approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In rats with an intact microbiota, SD had a limited effect on MCAO\u2010induced ischemic injury. Strikingly, in ABX\u2010induced dysbiosis, SD\u2010exposed rats subjected to MCAO displayed more severe motor deficits, larger infarct volumes, heightened inflammation, and decreased expression of key intestinal and BBB proteins. Microbiota analysis identified\n                      <jats:italic>Akkermansia<\/jats:italic>\n                      as a potential key mediator, whose abundance was significantly decreased in the ABX\u2009+\u2009SD\u2009+\u2009MCAO group and negatively correlated with infarct size. Subsequent metabolomics profiling revealed a distinct dysregulation of\n                      <jats:italic>Akkermansia<\/jats:italic>\n                      \u2010associated metabolites (including PG(14:0\/15:0), 3\u2010Methylbutylamine, N\u2010Acetylcytidine, and N\u2010Methylisoleucine).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      In conclusion, our study proposes a mechanism whereby SD worsens stroke outcomes by depleting\n                      <jats:italic>Akkermansia<\/jats:italic>\n                      and disrupting metabolic homeostasis.\n                    <\/jats:p>\n                  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