{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T10:59:30Z","timestamp":1792407570664,"version":"4.4.0"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T00:00:00Z","timestamp":1574812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["201703073000395"],"award-info":[{"award-number":["201703073000395"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81271205"],"award-info":[{"award-number":["81271205"]}],"id":[{"id":"10.13039\/501100001809","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":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Perioperative neurocognitive disorders have been widely recognized as common adverse events after surgical intervention. Aging is one of the most important independent risk factors for worsened cognitive outcome, and this deterioration is linked to exacerbated microglia\u2010mediated neuroinflammation in the aged brain. Under pathological stimulation, microglia are capable of polarizing toward proinflammatory M1 and anti\u2010inflammatory M2 phenotypes. In the present study, we examined how aging affects microglial responses and neuroinflammation following peripheral surgery. Adult (2\u20103\u00a0months) and aged (18\u00a0months old) male C57\/BL6 mice\u00a0were subjected to tibial fracture or sham surgery. Aged\u00a0mice exhibited\u00a0higher level of tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) and interleukin\u20101\u03b2 (IL\u20101\u03b2) in the hippocampus. The expression of synaptic protein synaptophysin (SYP) was also markedly reduced in the aged brain after the surgery. Both adult and aged mice showed significant increases in M1 microglial polarization (CD16\/32). In contrast, tibial fracture surgery induced a decreased M2 microglial polarization (CD206, Ym1\/2, Arg1) in aged brain but enhanced M2 microglial polarization in adult brain. Aged mice have upregulated voltage\u2010gated proton channel (Hv1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit expression compared with adult mice. The percentage of CD16\/32\u2010positive M1 microglia colabeling with Hv1 was higher in aged mice after tibial fracture surgery. Thus, Hv1\/NADPH oxidase upregulation in the aged brain may shift the dynamic equilibrium of microglial activation toward M1 polarization and exaggerate postoperative neuroinflammatory responses after peripheral surgical intervention.<\/jats:p>","DOI":"10.1111\/cns.13271","type":"journal-article","created":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T08:56:24Z","timestamp":1574844984000},"page":"374-384","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Aging alters Hv1\u2010mediated microglial polarization and enhances neuroinflammation after peripheral surgery"],"prefix":"10.1111","volume":"26","author":[{"given":"Zhi\u2010jing","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Peking University Shenzhen Hospital Shenzhen China"},{"name":"Shantou University Medical College Shantou 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