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Lipopolysaccharide (LPS) stimulates innate immune reactions and is used as an in vivo animal model for the investigation of inflammation. Meclizine (MCLZ) is a histamine antagonist with potential neuroprotective qualities. Forty adult male Swiss albino mice were divided into four groups (n\u2009=\u200910). Group 1 served as a control negative group. Groups 2\u20134 were injected with LPS (5\u00a0mg\/kg; i.p). Group 2 served as LPS-control. Groups 3 &amp; 4 were given MCLZ (12.5 &amp; 25\u00a0mg\/kg; p.o) respectively for 14 days. LPS administration resulted in significant neuroinflammation in mice as was revealed by significant inflammatory histopathological changes and positive immunohistochemical staining of glial fibrillary acidic proteins (GFAP) accompanied by significant elevations of brain tissue contents of interleukin-1-beta (IL-1\u03b2), tumor necrosis factor-alpha (TNF-\u03b1), nuclear factor kappa-beta (NF-\u03ba\u03b2), protein kinase B (AKT), extracellular signal-regulated kinase (ERK) and C-Jun N-Terminal Kinases (JNK). MCLZ treatment significantly down-regulated all the aforementioned parameters in mice brains. Moreover, MCLZ treatment ameliorated the inflammatory histopathological changes and GFAP immunostaining in brain tissues. The current study identifies for the first time the protective anti-neuroinflammatory effects of MCLZ against LPS-induced neuroinflammation in mice. MCLZ protected against neuroinflammation via the amelioration of inflammatory histopathological changes as well as neuronal GFAP immunostaining and down-regulated the AKT\/NF-\u03ba\u03b2\/ERK\/JNK signaling pathway. MCLZ is anticipated as a potential protective candidate for the addition to the treatment protocol of neuroinflammation.<\/jats:p>","DOI":"10.1007\/s11011-023-01295-3","type":"journal-article","created":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T09:02:23Z","timestamp":1695286943000},"page":"2797-2806","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Meclizine moderates lipopolysaccharide-induced neuroinflammation in mice through the regulation of AKT\/ NF-\u03ba\u03b2\/ERK\/JNK signaling pathway"],"prefix":"10.1007","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5765-350X","authenticated-orcid":false,"given":"Rasha E.","family":"Mostafa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7679-5968","authenticated-orcid":false,"given":"Gihan F.","family":"Asaad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,21]]},"reference":[{"key":"1295_CR1","doi-asserted-by":"crossref","unstructured":"Anfinogenova ND, Quinn MT, Schepetkin IA, Atochin DN (2020) Alarmins and c-Jun N-terminal kinase (JNK) signaling in neuroinflammation cells. 9:2350","DOI":"10.3390\/cells9112350"},{"key":"1295_CR2","first-page":"1522","volume":"25","author":"GF Asaad","year":"2022","unstructured":"Asaad GF, Mostafa RE (2022) Lactoferrin mitigates ethanol-induced gastric ulcer via modulation of ROS\/ICAM-1\/Nrf2 signaling pathway in Wistar rats. 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