{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T14:33:45Z","timestamp":1793025225608,"version":"4.5.0"},"reference-count":58,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T00:00:00Z","timestamp":1697155200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82001166"],"award-info":[{"award-number":["82001166"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171186"],"award-info":[{"award-number":["82171186"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2021J01385"],"award-info":[{"award-number":["2021J01385"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2021J01366"],"award-info":[{"award-number":["2021J01366"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Dexmedetomidine (DEX) has been reported to alleviate hypoxic\u2013ischemic brain damage (HIBD) in neonates. This study aimed to investigate whether DEX improves cognitive impairment by promoting hippocampal neurogenesis via the BDNF\/TrkB\/CREB signaling pathway in neonatal rats with HIBD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>HIBD was induced in postnatal day 7 rats using the Rice\u2010Vannucci method, and DEX (25\u2009\u03bcg\/kg) was administered intraperitoneally immediately after the HIBD induction. The BDNF\/TrkB\/CREB pathway was regulated by administering the TrkB receptor antagonist ANA\u201012 through intraperitoneal injection or by delivering adeno\u2010associated virus (AAV)\u2010shRNA\u2010BDNF via intrahippocampal injection. Western blot was performed to measure the levels of BDNF, TrkB, and CREB. Immunofluorescence staining was utilized to identify the polarization of astrocytes and evaluate the levels of neurogenesis in the dentate gyrus of the hippocampus. Nissl and TTC staining were performed to evaluate the extent of neuronal damage. The MWM test was conducted to evaluate spatial learning and memory ability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The levels of BDNF and neurogenesis exhibited a notable decrease in the hippocampus of neonatal rats after HIBD, as determined by RNA\u2010sequencing technology. Our results demonstrated that treatment with DEX effectively increased the protein expression of BDNF and the phosphorylation of TrkB and CREB, promoting neurogenesis in the dentate gyrus of the hippocampus in neonatal rats with HIBD. Specifically, DEX treatment significantly augmented the expression of BDNF in hippocampal astrocytes, while decreasing the proportion of detrimental A1 astrocytes and increasing the proportion of beneficial A2 astrocytes in neonatal rats with HIBD. Furthermore, inhibiting the BDNF\/TrkB\/CREB pathway using either ANA\u201012 or AAV\u2010shRNA\u2010BDNF significantly counteracted the advantageous outcomes of DEX on hippocampal neurogenesis, neuronal survival, and cognitive improvement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>DEX promoted neurogenesis in the hippocampus by activating the BDNF\/TrkB\/CREB pathway through the induction of polarization of A1 astrocytes toward A2 astrocytes, subsequently mitigating neuronal damage and cognitive impairment in neonates with HIBD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.14486","type":"journal-article","created":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T04:53:22Z","timestamp":1697172802000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Dexmedetomidine alleviates cognitive impairment by promoting hippocampal neurogenesis via BDNF\/TrkB\/CREB signaling pathway in hypoxic\u2013ischemic neonatal rats"],"prefix":"10.1111","volume":"30","author":[{"given":"Xiaohui","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjie","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital  Fuzhou 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Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxue","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiuyun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Fujian Provincial Key Laboratory of Emergency Medicine  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of 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