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We further correlated the levels of differential metabolites with severity\u2010related clinical parameters, including the normal pressure hydrocephalus grading scale (NPHGS). We then established kaolin\u2010induced hydrocephalus in mice and treated them using N\u2010acetylmannosamine (ManNAc), a precursor of Neu5Ac. We examined brain Neu5Ac, astrocyte polarization, demyelination, and neurobehavioral outcomes to explore its therapeutic effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three metabolites were significantly altered in NPH patients. Only decreased Neu5Ac levels were correlated with NPHGS scores. Decreased brain Neu5Ac levels have been observed in hydrocephalic mice. Increasing brain Neu5Ac by ManNAc suppressed the activation of astrocytes and promoted their transition from A1 to A2 polarization. ManNAc also attenuated the periventricular white matter demyelination and improved neurobehavioral outcomes in hydrocephalic mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Increasing brain Neu5Ac improved the neurological outcomes associated with the regulation of astrocyte polarization and the suppression of demyelination in hydrocephalic mice, which may be a potential therapeutic strategy for NPH.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14253","type":"journal-article","created":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T09:54:29Z","timestamp":1684922069000},"page":"3183-3198","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Increasing brain N\u2010acetylneuraminic acid alleviates hydrocephalus\u2010induced neurological deficits"],"prefix":"10.1111","volume":"29","author":[{"given":"Zhangyang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqun","family":"Nie","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences Chinese Academy of Sciences (CAS)  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Gao","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences Chinese Academy of Sciences (CAS)  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmin","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurology, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4915-9819","authenticated-orcid":false,"given":"Yanqin","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of the State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences Chinese Academy of Sciences (CAS)  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5135-4210","authenticated-orcid":false,"given":"Jing","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Neurology, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Zhongshan Hospital Fudan University  Shanghai China"},{"name":"Department of the State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2176\/nmc.st.2020-0292"},{"key":"e_1_2_9_3_1","unstructured":"DasJM BiagioniMC.Normal pressure hydrocephalus. 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