{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:29:54Z","timestamp":1791433794968,"version":"4.3.3"},"reference-count":83,"publisher":"Georg Thieme Verlag KG","issue":"16","license":[{"start":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T00:00:00Z","timestamp":1618358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Perinatol"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:p>Neonatal hypoxic\u2013ischemic encephalopathy (HIE) causes permanent motor deficit \u201ccerebral palsy (CP),\u201d and may result in significant disability and death. Therapeutic hypothermia (TH) had been established as the first effective therapy for neonates with HIE; however, TH must be initiated within the first 6\u2009hours after birth, and the number needed to treat is from 9 to 11 to prevent brain damage from HIE. Therefore, additional therapies for HIE are highly needed. In this review, we provide an introduction on the mechanisms of HIE cascade and how TH and cell therapies such as umbilical cord blood cells and mesenchymal stromal cells (MSCs), especially umbilical cord-derived MSCs (UC-MSCs), may protect the brain in newborns, and discuss recent progress in regenerative therapies using UC-MSCs for neurological disorders.<\/jats:p><jats:p>The brain damage process \u201cHIE cascade\u201d was divided into six stages: (1) energy depletion, (2) impairment of microglia, (3) inflammation, (4) excitotoxity, (5) oxidative stress, and (6) apoptosis in capillary, glia, synapse and\/or neuron. The authors showed recent 13 clinical trials using UC-MSCs for neurological disorders.<\/jats:p><jats:p>The authors suggest that the next step will include reaching a consensus on cell therapies for HIE and establishment of effective protocols for cell therapy for HIE.<\/jats:p><jats:p>Key Points<\/jats:p>","DOI":"10.1055\/s-0041-1726451","type":"journal-article","created":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T23:15:14Z","timestamp":1618442114000},"page":"1754-1763","source":"Crossref","is-referenced-by-count":17,"title":["Preventing Brain Damage from Hypoxic\u2013Ischemic Encephalopathy in Neonates: Update on Mesenchymal Stromal Cells and Umbilical Cord Blood Cells"],"prefix":"10.1055","volume":"39","author":[{"given":"Makoto","family":"Nabetani","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Yodogawa Christian Hospital, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6648-1271","authenticated-orcid":false,"given":"Takeo","family":"Mukai","sequence":"additional","affiliation":[{"name":"Department of Cell Processing and Transfusion, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruo","family":"Shintaku","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Osaka City University, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2021,4,14]]},"reference":[{"issue":"04","key":"ref1","first-page":"CD003311","article-title":"Cooling for newborns with hypoxic ischaemic encephalopathy","author":"S Jacobs","year":"2007","journal-title":"Cochrane Database Syst 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