{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:14:46Z","timestamp":1791400486864,"version":"4.3.3"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Neonatal hypoxic\u2010ischemic brain injury (HIBI) caused by perinatal asphyxia is a primary cause of long\u2010term neurological morbidity. Hypothermia is the sole available clinical intervention despite its limited efficacy. Intranasal mesenchymal stem cells (MSCs) show promise for the treatment of HIBI. This study explores the efficacy, migration, treatment window, and therapeutic mechanisms of intranasally applied Wharton's jelly\u2010derived MSCs (WJ\u2010MSCs) in a neonatal HIBI mouse model, and assesses its therapeutic benefit in conjunction with hypothermia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Nine\u2010day\u2010old C57BL\/6 mice underwent hypoxia\u2010ischemia (HI), with or without hypothermia, and were intranasally dosed with 0.1 to 2.0\u2009\u00d7\u200910\n                      <jats:sup>6<\/jats:sup>\n                      WJ\u2010MSCs, at 3 or 10\u2009days post\u2010HI. WJ\u2010MSCs were traced using different techniques. Neurogenesis was examined 2\u2009days post\u2010treatment. Neuroinflammation, sensorimqotor outcome, and neuronal tissue loss was assessed 28\u2009days post\u2010HI. Additionally, anti\u2010inflammatory and neuroregenerative properties of WJ\u2010MSCs were investigated in non\u2010contact co\u2010cultures with microglia and neural stem cells, and by secretome profiling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Intranasally delivered WJ\u2010MSCs reduced HI\u2010induced lesion size and sensorimotor impairments. WJ\u2010MSCs expressed multiple receptors for upregulated chemokines in the HI\u2010lesion, and migrated from the nasal cavity into the meninges and brain parenchyma. WJ\u2010MSCs secreted a broad spectrum of immunomodulatory and neuroregenerative proteins, and inhibited neuroinflammation and boosted neuroregeneration\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      . WJ\u2010MSC potency was sustained across different donors. Importantly, intranasal WJ\u2010MSCs augmented the therapeutic benefits of hypothermia following neonatal HIBI in mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>This study provides new translational evidence that intranasal WJ\u2010MSCs, either alone or in combination with hypothermia, mitigate the consequences of neonatal HIBI by resolving inflammation and boosting neurorepair through their secretome. ANN NEUROL 2025;98:1380\u20131394<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78000","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T09:43:53Z","timestamp":1756201433000},"page":"1380-1394","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Intranasal Wharton's Jelly\u2010Derived Mesenchymal Stem Cell Therapy, Alone or in Conjunction With Therapeutic Hypothermia, Alleviates Neonatal Hypoxic\u2010Ischemic Brain Injury in Mice"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1265-7897","authenticated-orcid":false,"given":"Caroline G. 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