¹Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Department of Anesthesiology and Pain Medicine, 430030 Wuhan, CHINA
²The Third Affiliated Hospital of Xinjiang Medical University, Department of Anesthesiology, 830000 Urumqi, CHINA
³Jiangxi Maternal and Child Health Hospital, Department of Anesthesiology, 330003 Nanchang, CHINA DOI : 10.9775/kvfd.2025.35579 We aimed to investigate whether dexmedetomidine (Dex) alleviates hypoxic-ischemic brain damage (HIBD) in neonatal mice and to explore the potential involvement of AMPK-related mechanisms. C57BL/6 neonatal mice were randomly assigned into a sham group, an HIBD group, an HIBD + Dex group, and an HIBD + Dex + Compound C (CC) group. Neurological deficits were scored, brain water content was detected and cerebral infarction areas were determined via 2,3,5-triphenyltetrazolium chloride staining. Hematoxylin-eosin staining was performed to detect the pathological changes in brain tissues. Compared with the sham group, HIBD mice showed markedly increased neurological deficit scores, brain water content, infarct area, ROS, and MDA levels, accompanied by reduced GSH-Px, SOD activity, a lower p-AMPK/AMPK ratio, and decreased UCP2 expression (p<0.05). Dex treatment significantly improved neurological function, reduced cerebral edema and infarction, decreased oxidative stress markers, and enhanced antioxidant enzyme activity, together with increased AMPK phosphorylation and UCP2 expression compared with HIBD (p<0.05). Notably, co-administration of Compound C partially attenuated the neuroprotective and antioxidative effects of Dex, supporting the involvement of AMPK-dependent mechanisms. Although UCP2 expression was altered in parallel with AMPK activity, the present data do not directly establish UCP2 as a causal mediator. Overall, these findings suggest that Dex mitigates oxidative stress and neuronal injury in neonatal HIBD, potentially through AMPK-associated pathways, with UCP2 representing a putative downstream component. Keywords : AMPK, Brain damage, Dexmedetomidine, Neonate, Oxidative stress