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Cortistatin-14 is a neuropeptide structurally resembling somastostatin, which has been proven to play a crucial role in sepsis. The present study aimed to explore the neuroprotective role of cortistatin-14 in sepsis-associated encephalopathy and its underlying mechanisms in a mouse model. A septic mice model was established using the cecal ligation and puncture (CLP) method. The novel object recognition test (NORT), open field test (OFT), elevated plus maze test (EPMT), and tail suspension test (TST) were used to explore the behavioral performance of the mice. Transmission electron microscopy was used to observe the microstructure of the blood-brain barrier (BBB). Evans Blue staining was used to examine the integrity of the BBB. Immunofluorescence was used to examine the morphology and infiltration of microglia. A multiplex cytokine bead array assay was used to determine cytokine and chemokine levels in mouse serum and brain tissues. NORT revealed that cortistatin treatment improved cognitive impairment in septic mice. OFT, EPMT, and TST indicated that cortistatin-14 relieved the anxiety-related behaviors of CLP mice. In addition, cortistatin-14 treatment decreased the levels of various inflammatory cytokines, including interleukin-1\u03b2, interleukin-6, interferon-\u03b3, and tumor necrosis factor-\u03b1 in both the serum and brain of septic mice. Cortistatin reduced sepsis-induced blood-brain barrier disruption and inhibited microglial activation after the onset of sepsis. Cortistatin exerts neuroprotective effects against SAE and cognitive dysfunction in a CLP-induced mouse model of sepsis.<\/jats:p>","DOI":"10.1155\/2022\/3334145","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T21:05:08Z","timestamp":1663103108000},"page":"1-10","source":"Crossref","is-referenced-by-count":19,"title":["Cortistatin-14 Exerts Neuroprotective Effect Against Microglial Activation, Blood-brain Barrier Disruption, and Cognitive Impairment in Sepsis-associated Encephalopathy"],"prefix":"10.1155","volume":"2022","author":[{"given":"Qiang","family":"Wen","sequence":"first","affiliation":[{"name":"Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong First Medical University, Jinan 250021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong First Medical University, Jinan 250021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinchao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong First Medical University, Jinan 250021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Taian Hospital of Traditional Chinese Medicine, Tai'an 271000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangchen","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong First Medical University, Jinan 250021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanrong","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong First Medical University, Jinan 250021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongsheng","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong First Medical University, Jinan 250021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8852-6602","authenticated-orcid":true,"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong First Medical University, Jinan 250021, China"},{"name":"School of Medicine, Shandong University, Jinan 250012, China"},{"name":"Shandong University of Traditional Chinese Medicine, Jinan 250011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"issue":"5","key":"1","first-page":"828","article-title":"Epidemiological features and risk factors of sepsis-associated encephalopathy in intensive care unit patients: 2008-2011","volume":"125","author":"L. 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