{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:56:05Z","timestamp":1791266165080,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Developmental Neurobiology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Neonatal hypoxic\u2010ischemic brain damage (HIBD) is the leading cause of neonatal death and long\u2010term neurological dysfunction. Dexmedetomidine (DEX) has been shown to have neuroprotective effects, but its mechanisms in HIBD remain incompletely understood. This study aimed to explore whether DEX inhibits neuroinflammation and pyroptosis via activating adenosine monophosphate\u2010activated protein kinase (AMPK)\/sirtuin 1 (SIRT1) axis, thereby reducing HIBD. A HIBD model was established. Histological staining observed the pathological changes and neuronal survival. Primary cortical neurons were cultured to establish an oxygen\u2013glucose deprivation\/reoxygenation (OGD\/R) model. DEX was used for intervene, and siAMPK was transfected to knock down AMPK expression. Inflammatory and oxidative stress indicators within brain tissue and neuronal cells were measured using enzyme\u2010linked immunosorbent assay (ELISA) and biochemical kits. The AMPK\/SIRT1 pathway and pyroptosis protein expressions were evaluated using fluorescence staining and Western blot. DEX dose\u2010dependently reduced cerebral infarction volume, improved cerebral cortex pathological damage, enhanced neuronal nuclei (NeuN) positive neurons, decreased interleukin (IL)\u20106 and malondialdehyde (MDA) contents, enhanced superoxide dismutase (SOD) activity, and inhibited terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)\/cleaved Caspase\u20101 double positive cells and N\u2010terminal domain of Gasdermin D (GSDMD\u2010N) protein expressions. DEX significantly upregulated p\u2010AMPK and SIRT1 expression, whereas the AMPK inhibitor Compound C reversed the neuroprotective effect of DEX. In vitro experiments confirmed that DEX increased neuronal cell viability, reduced lactate dehydrogenase (LDH) release and propidium iodide (PI)\u2010positive cell rate, reduced oxidative stress, and inhibited inflammatory factor release and pyroptosis\u2010related protein expression. AMPK knockdown significantly reversed this axis activation by DEX and attenuated the neuroprotective effect of DEX. In conclusion, DEX improved neurological function in HIBD rats via the activating AMPK\/SIRT1 pathway, reducing neuroinflammation and inhibiting neuronal pyroptosis.<\/jats:p>","DOI":"10.1002\/dneu.70067","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:34:18Z","timestamp":1791264858000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dexmedetomidine Activates AMPK\/SIRT1 Pathway to Reduce Inflammatory Levels and Neuronal Pyroptosis to Alleviate Neonatal Hypoxic\u2010Ischemic Brain Damage"],"prefix":"10.1002","volume":"86","author":[{"given":"Jinping","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Neonatology Hangzhou Women's Hospital (Hangzhou Maternity and Child Health Care Hospital)  Hangzhou Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Neonatology Hangzhou Women's Hospital (Hangzhou Maternity and Child Health Care Hospital)  Hangzhou Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yejun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neonatology Hangzhou Women's Hospital (Hangzhou Maternity and Child Health Care Hospital)  Hangzhou Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minzhi","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neonatology Hangzhou Women's Hospital (Hangzhou Maternity and Child Health Care Hospital)  Hangzhou Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weinong","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Neonatology Hangzhou Women's Hospital (Hangzhou Maternity and Child Health Care Hospital)  Hangzhou Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhong","family":"Li","sequence":"additional","affiliation":[{"name":"Hangzhou Zunxiang Biotechnology Co., Ltd  Hangzhou Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengzao","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neonatology Hangzhou Women's Hospital (Hangzhou Maternity and Child Health Care Hospital)  Hangzhou Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.64229\/ps9nz775","article-title":"Intranasal Herbal Neurotherapeutics in Neurodegenerative Disorders: Preclinical Advances and Translational Implications","volume":"1","author":"Gangadharan T.","year":"2026","journal-title":"Neuroscience Research and Clinical Practice"},{"key":"e_1_2_14_3_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.62382\/jcbt.v3i3.121","article-title":"Apoptosis Dysregulation in Prostate Cancer: The BAX\/BCL\u20102 Dynamics and Caspase Cascade Activation Networks","volume":"3","author":"Ali A. 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