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Neural stem cell (NSC) engrafting is an emerging therapeutic strategy with considerable promise that, unfortunately, is severely compromised by limited cell functionality after in vivo transplantation. This groundbreaking report demonstrates that metabolic glycoengineering (MGE) using the \u201cAc<jats:sub>5<\/jats:sub>ManNTProp (TProp)\u201d monosaccharide analog stimulates the Wnt\/\u03b2\u2010catenin pathway, improves cell adhesion, and enhances neuronal differentiation in human NSCs in vitro thereby substantially increasing the therapeutic potential of these cells. For the first time, MGE significantly enhances NSC efficacy for treating ischemic brain injury after asphyxia CA in rats. In particular, neurological deficit scores and neurobehavioral tests experience greater improvements when the therapeutic cells are pretreated with TProp than with \u201cstand\u2010alone\u201d NSC therapy. Notably, the TProp\u2010NSC group exhibits significantly stronger neuroprotective functions including enhanced differentiation, synaptic plasticity, and reduced microglia recruitment; furthermore, Wnt pathway agonists and inhibitors demonstrate a pivotal role for Wnt signaling in the process. These findings help establish MGE as a promising avenue for addressing current limitations associated with NSC transplantation via beneficially influencing neural regeneration and synaptic plasticity, thereby offering enhanced therapeutic options to boost brain recovery following global ischemia.<\/jats:p>","DOI":"10.1002\/adfm.202309866","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T23:31:14Z","timestamp":1703287874000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Metabolically Glycoengineered Neural Stem Cells Boost Neural Repair After Cardiac Arrest"],"prefix":"10.1002","volume":"34","author":[{"given":"Jian","family":"Du","sequence":"first","affiliation":[{"name":"Department of Neurosurgery University of Maryland School of Medicine  Baltimore MD 21201 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery University of Maryland School of Medicine  Baltimore MD 21201 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subash","family":"Marasini","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery University of Maryland School of Medicine  Baltimore MD 21201 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuoran","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery University of Maryland School of Medicine  Baltimore MD 21201 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kris","family":"Dammen\u2010Brower","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering The Johns Hopkins School of Medicine  Baltimore MD 21205 USA"},{"name":"Translational Cell and Tissue Engineering Center The Johns Hopkins School of Medicine  Baltimore MD 21231 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin J.","family":"Yarema","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering The Johns Hopkins School of Medicine  Baltimore MD 21205 USA"},{"name":"Translational Cell and Tissue Engineering Center The Johns Hopkins School of Medicine  Baltimore MD 21231 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1445-8525","authenticated-orcid":false,"given":"Xiaofeng","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery University of Maryland School of Medicine  Baltimore MD 21201 USA"},{"name":"Department of Biomedical Engineering The Johns Hopkins School of Medicine  Baltimore MD 21205 USA"},{"name":"Department of Orthopedics University of Maryland School of Medicine  Baltimore MD 21201 USA"},{"name":"Department of Anatomy and Neurobiology University of Maryland School of Medicine  Baltimore MD 21201 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,12,22]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001013"},{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCOUTCOMES.119.005580"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resplu.2022.100229"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.7809"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCC.0000000000001023"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975\u2010023\u201001163\u20103"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-022-01047-y"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-021-06548-2"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.5853\/jos.2019.03048"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-020-10067-w"},{"key":"e_1_2_10_7_2","author":"Wang Z.","year":"2019","journal-title":"Annu. 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