{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T04:14:34Z","timestamp":1776572074800,"version":"3.51.2"},"reference-count":66,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T00:00:00Z","timestamp":1649376000000},"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":["81571479"],"award-info":[{"award-number":["81571479"]}],"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":["82071688"],"award-info":[{"award-number":["82071688"]}],"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":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>White matter damage (WMD) is the main cause of cerebral palsy and cognitive impairment in premature infants. Although caffeine has been shown to possess neuroprotective effects in neonatal rats with hypoxic\u2010ischemic WMD, the mechanisms underlying these protective effects are unclear. Herein, proteins modulated by caffeine in neonatal rats with hypoxic\u2010ischemic WMD were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We identified differential proteins and performed functional enrichment analyses between the Sham, hypoxic\u2010ischemic WMD (HI), and HI+caffeine\u2010treated WMD (Caffeine) groups. Confirmed the changes and effect of proteins in animal models and determined cognitive impairment via water maze experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In paraventricular tissue, 47 differential proteins were identified between the Sham, HI, and Caffeine groups. Functional enrichment analyses showed that these proteins were related to myelination and axon formation. In particular, the myelin basic protein (MBP), proteolipid protein, myelin\u2010associated glycoprotein precursor, and sirtiun 2 (SIRT2) levels were reduced in the hypoxic\u2010ischemic WMD group, and this effect could be prevented by caffeine. Caffeine alleviated the hypoxic\u2010ischemic WMD\u2010induced cognitive impairment and improved MBP, synaptophysin, and postsynaptic density protein 95 protein levels after hypoxic\u2010ischemic WMD by preventing the HI\u2010induced downregulation of SIRT2; these effects were subsequently attenuated by the SIRT2 inhibitor AK\u20107.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Caffeine may have clinical applications in the management of prophylactic hypoxic\u2010ischemic WMD; its effects may be mediated by proteins related to myelin development and synapse formation through SIRT2.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13834","type":"journal-article","created":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T09:30:04Z","timestamp":1649410204000},"page":"1019-1032","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Proteomic analysis of the effects of caffeine in a neonatal rat 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