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This study looked at the potential neuroprotective benefits of cilostazol, a phosphodiesterase inhibitor, against LPS\u2010induced hippocampus damage in rodents and the principal molecular involvement of AKT\/GSK3<jats:italic>\u03b2<\/jats:italic>\/CREB signaling pathways. Behavioral tests revealed that cilostazol successfully corrected LPS\u2010induced neurobehavioral impairments. Furthermore, cilostazol therapy lowered hippocampal levels of amyloid beta 1\u201342 (A<jats:italic>\u03b2<\/jats:italic>1\u201042) and p\u2010tau protein, both of which are critical pathological indicators of neurodegenerative disorders. Furthermore, cilostazol administration suppressed LPS\u2010induced rises in hippocampus caspase\u20103 and NF\u2010<jats:italic>\u03ba<\/jats:italic>B levels while elevating rat B\u2010cell\/lymphoma 2 (BCL2) and brain\u2010derived neurotrophic factor (BDNF) levels, which are implicated in neuronal survival and synaptic plasticity. Cilostazol treatment also restored the decreased phosphorylation of protein kinase B (p\u2010AKT) and reduced the elevated levels of phosphorylated glycogen synthase kinase\u20103 beta (p\u2010GSK3<jats:italic>\u03b2<\/jats:italic>) and cAMP response element\u2010binding protein (CREB) in the hippocampus of LPS\u2010treated rats. Histopathological examination revealed that cilostazol ameliorated LPS\u2010induced brain damage with reduced neuronal loss and gliosis. Immunohistochemistry analysis showed a decrease in Iba\u20101 expression, indicating a reduction in microglial activation in the cilostazol\u2010treated group compared to the LPS group. The findings advocate that cilostazol exerts neuroprotective effects against LPS\u2010induced hippocampal injury by modulating the AKT\/GSK3<jats:italic>\u03b2<\/jats:italic>\/CREB pathway and curbing neuroinflammation. Cilostazol may hold promise as a therapeutic agent for neuroinflammatory conditions associated with neurodegenerative diseases.<\/jats:p>","DOI":"10.1155\/2024\/3465757","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T12:18:57Z","timestamp":1727353137000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cilostazol Combats Lipopolysaccharide\u2010Induced Hippocampal Injury in Rats: Role of AKT\/GSK3<i>\u03b2<\/i>\/CREB Curbing Neuroinflammation"],"prefix":"10.1155","volume":"2024","author":[{"given":"Doaa 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