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This study investigated the effects of Dex on microglial activation, neuroinflammation, and apoptosis, and the role of Api in hippocampal neurogenesis, along with its combined effects via the miR\u201015a\/ROCK\u20101\/ERK1\/2\/CREB\/BDNF signaling cascade. Male Sprague Dawley rats were randomly assigned into: a normal control group, Dex and Api\u2010control groups, which received Dex or Api daily for 30 days, an MTX\u2010only group that received MTX and leucovorin (LCV), Dex or Api cotreated groups received either Dex or Api with MTX and LCV, and a Dex\u2009+\u2009Api cotreated group received both drugs with MTX and LCV. Dex improved cognitive function by attenuating microglial activation. Api mitigated hippocampal neurogenesis, as shown by decreased Ki\u201067 and doublecortin (DCX) expression. Compared with Dex or Api alone, the combined treatment had more favorable effects on novel object recognition (NOR), miR\u201015a, ROCK\u20101, ERK1\/2, histopathological changes, and Ki\u201067 neurogenesis marker over Api or Dex monotherapy, and improved CREB\/BDNF signaling over Dex alone. However, no additional favorable effects on microglial activation, redox balance, IL\u20101\u03b2, or apoptosis were observed. The combination of Dex and Api exhibits more pronounced neuroprotective effects by potentiating modulation of the miR\u201015a\/ROCK\u20101\/ERK1\/2\/CREB\/BDNF signaling cascade, improving cognitive behavior, and enhancing hippocampal neurogenesis.<\/jats:p>","DOI":"10.1155\/np\/9434180","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T10:56:16Z","timestamp":1778496976000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dexmedetomidine and Apigenin Combination Mitigates Memory Deficits Caused by Microglial Activation and Hippocampal Neurogenesis Impairment in Methotrexate\u2010Induced Chemo\u2010Brain in Rats"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8935-0183","authenticated-orcid":false,"given":"Einas M.","family":"Yousef","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0475-7388","authenticated-orcid":false,"given":"Omar Mohsen","family":"Eldemerdash","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3942-0275","authenticated-orcid":false,"given":"Mahmoud A.","family":"Senousy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9806-826X","authenticated-orcid":false,"given":"Mohamed","family":"Taha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6776-4644","authenticated-orcid":false,"given":"Haidy","family":"Mohammed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7736-8469","authenticated-orcid":false,"given":"Ismail Mohamed","family":"Elshaffei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"e_1_2_14_1_2","doi-asserted-by":"publisher","DOI":"10.1177\/2055102919832234"},{"key":"e_1_2_14_2_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.76.4696"},{"key":"e_1_2_14_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13081939"},{"key":"e_1_2_14_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14211"},{"key":"e_1_2_14_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/NHH.0000000000000203"},{"key":"e_1_2_14_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms16011772"},{"key":"e_1_2_14_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-021-05977-7"},{"key":"e_1_2_14_8_2","volume-title":"PDQ Cancer Information Summaries","author":"PPTE Board","year":"2022"},{"key":"e_1_2_14_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000001374"},{"key":"e_1_2_14_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2019.02.010"},{"key":"e_1_2_14_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu11040936"},{"key":"e_1_2_14_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03299-7"},{"key":"e_1_2_14_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010766"},{"key":"e_1_2_14_14_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.06-10-02950.1986"},{"key":"e_1_2_14_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2012.09.003"},{"key":"e_1_2_14_16_2","doi-asserted-by":"publisher","DOI":"10.1155\/sci\/8440764"},{"key":"e_1_2_14_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.10.049"},{"key":"e_1_2_14_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2005.02.003"},{"key":"e_1_2_14_19_2","doi-asserted-by":"crossref","unstructured":"Ortega-Mart\u00ednezS. 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