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Silibinin possesses antioxidant, anti-inflammatory, and neuroprotective properties; however, its potential to facilitate recovery following prolonged SD remains unclear. This study investigated the effects of silibinin on cognitive dysfunction and hippocampal alterations induced by 5\u00a0days of SD, with or without a subsequent 24-h recovery period, in rats. Forty-eight adult male rats were allocated to control (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200916), SD (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098), SD\u2009+\u2009recovery (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098), SD\u2009+\u2009silibinin (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098), and SD\u2009+\u2009silibinin\u2009+\u2009recovery (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098) groups. Cognitive performance was assessed using the Open Field Test, Morris Water Maze, and Y-Maze. Serum oxidative stress (MDA and SOD), inflammatory (TNF-\u03b1 and IL-6), and hormonal biomarkers were evaluated. Hippocampal BDNF and CaMKII levels, histopathological changes, and the immunohistochemical expression of PCNA, synaptophysin, and GFAP were also assessed. SD significantly impaired cognitive performance (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05), increased oxidative stress and inflammatory cytokines (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.01), altered stress-related hormones (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05), decreased hippocampal BDNF and CaMKII levels (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001) and induced marked histopathological and immunohistochemical changes. A 24-h recovery period partially ameliorated these alterations. Silibinin treatment significantly attenuated the SD-induced behavioral, biochemical, hormonal, histopathological, and immunohistochemical alterations (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05), with further improvement following recovery sleep (\n                    <jats:italic>P\u2009<\/jats:italic>\n                    &lt;\u20090.05), restoring most parameters to levels comparable to those of the control group. These findings suggest that silibinin protects against SD-induced cognitive dysfunction and hippocampal injury by attenuating oxidative stress, neuroinflammation, and neuroendocrine disturbances while enhancing recovery during subsequent recovery sleep.\n                  <\/jats:p>","DOI":"10.1007\/s12035-026-06195-y","type":"journal-article","created":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T06:16:35Z","timestamp":1791008195000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Silibinin Alleviates Cognitive Dysfunction, Biochemical Alterations, and Hippocampal Structural Changes Induced by 5 days of Sleep Deprivation with or Without a Subsequent 24-H Recovery in Rats"],"prefix":"10.1007","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8832-854X","authenticated-orcid":false,"given":"Dalia Fathy","family":"El Agamy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman Shehata","family":"El-Roghy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esam Omar","family":"Hendia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omnia. 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