{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T16:37:45Z","timestamp":1764175065772,"version":"3.40.5"},"reference-count":93,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T00:00:00Z","timestamp":1624320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81371195","81870851"],"award-info":[{"award-number":["81371195","81870851"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Postoperative delirium (POD) is a common post\u2010operative complication in elderly patients that is associated with increased morbidity and mortality. However, the neuropathogenesis of this complication remains unknown. The blood\u2013cerebrospinal fluid barrier (BCB) and brain\u2013blood barrier (BBB) are composed of tight junctions between cells that form physical barriers, and BBB damage plays an important role in the neuropathogenesis of POD. Nevertheless, the role of BCB in POD remains to be elucidated. Herein, we investigated the effect of adenosine A<jats:sub>2A<\/jats:sub>receptor (A<jats:sub>2A<\/jats:sub>R), a key regulator of the permeability of barriers, on surgery\u2010induced increased permeability of BCB and POD\u2010like behaviors. Open field, buried food, and Y maze tests were used to evaluate behavioral changes in rats after surgery. Levels of tight junction proteins, adherens junction proteins, A<jats:sub>2A<\/jats:sub>R, GTP\u2010RhoA, and ROCK2 in the choroid plexus were assessed by western blotting. The concentrations of NaFI and FITC\u2010dextran in the cerebrospinal fluid (CSF) were detected by fluorescence spectrophotometry. Transmission electron microscopy was applied to observe the ultrastructure of the choroid plexus. Surgery\/anesthesia decreased the levels of tight junction (e.g., ZO\u20101, occludin, and claudin1) proteins, increased concentrations of NaFI and FITC\u2010dextran in CSF, damaged the ultrastructure of choroid plexus, and induced POD\u2010like behaviors in rats. An A<jats:sub>2A<\/jats:sub>R antagonist alleviated POD\u2010like behaviors in rats. Furthermore, the A<jats:sub>2A<\/jats:sub>R antagonist increased the levels of tight junction proteins and restored the permeability of BCB in rats with POD. Fasudil, a selective Rho\u2010associated protein kinase 2 (ROCK2) inhibitor, ameliorated POD\u2010like behaviors induced by A<jats:sub>2A<\/jats:sub>R activation. Moreover, fasudil also abolished the increased levels of GTP\u2010RhoA\/ROCK2, decreased levels of tight junction proteins, and increased permeability of BCB caused by A<jats:sub>2A<\/jats:sub>R activation. Our findings demonstrate that A<jats:sub>2A<\/jats:sub>R might participate in regulating BCB permeability in rats with POD via the RhoA\/ROCK2 signaling pathway, which suggests the potential of A<jats:sub>2A<\/jats:sub>R as a therapeutic target for POD.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15436-fig-0010-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.15436","type":"journal-article","created":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T15:39:31Z","timestamp":1621957171000},"page":"980-996","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The adenosine A<sub>2A<\/sub>receptor alleviates postoperative delirium\u2010like behaviors by restoring blood cerebrospinal barrier permeability in rats"],"prefix":"10.1111","volume":"158","author":[{"given":"Lei","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Zhongnan Hospital of Wuhan University Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Zhongnan Hospital of Wuhan University Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Zhongnan Hospital of Wuhan University Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Zhongnan Hospital of Wuhan University Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zongze","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Zhongnan Hospital of Wuhan University Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5265-1142","authenticated-orcid":false,"given":"Mian","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Zhongnan Hospital of Wuhan University Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,6,22]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/EJA.0000000000000594"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cm.20472"},{"key":"e_1_2_12_4_1","first-page":"Ff01\u201005","article-title":"An experimental study to evaluate the effect of memantine in animal models of anxiety in swiss albino mice","volume":"9","author":"Bagewadi H. 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