{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:41:43Z","timestamp":1792204903286,"version":"4.4.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82160126"],"award-info":[{"award-number":["82160126"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Joint Project of Guizhou Medical University and Guizhong Biotechnology Co., Ltd","award":["HY2402"],"award-info":[{"award-number":["HY2402"]}],"id":[{"id":"https:\/\/ror.org\/035y7a716","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Science and Technology Fund of Guizhou Provincial Health Commission","award":["gzwkj2026-062"],"award-info":[{"award-number":["gzwkj2026-062"]}],"id":[{"id":"https:\/\/ror.org\/027yzwq33","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Science and Technology Fund of Guizhou Provincial Health Commission","award":["gzwkj2023-093"],"award-info":[{"award-number":["gzwkj2023-093"]}],"id":[{"id":"https:\/\/ror.org\/027yzwq33","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To explore the neuroprotective effect and molecular mechanism of human umbilical cord mesenchymal stem cells (hUC-MSCs) in preterm rats with intraventricular hemorrhage (IVH), and provide experimental basis for clinical treatment of neonatal IVH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Tissue block adherence method was used to isolate and culture hUC-MSCs, and P4 Sprague-Dawley premature rats were divided into sham, IVH model, and hUC-MSC treatment groups. Collagenase VIIS was injected to establish IVH model, and hUC-MSCs were injected into lateral ventricles. Cell colonization, body weight, neurobehavior, brain histology, apoptosis, and related molecular indicators were detected via fluorescence tracking, behavioral tests, staining, RT-PCR, Western blot (WB), and ELISA. Bioinformatics combined with ANA12 blocking assay verified core pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>hUC-MSCs survived in rat brain for at least 7\u2009days. Compared with the model group, the treatment group gained weight faster, neurobehavioral function was markedly improved, neuronal apoptosis decreased sharply, and brain tissue damage was alleviated. hUC-MSCs up-regulated anti-apoptotic, anti-inflammatory, antioxidant and neurogenesis-related molecules and activated BDNF\/TrkB\/CREB\/PI3K-Akt pathway; TrkB blockade reversed all protective effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>hUC-MSCs exert multi-target neuroprotection by activating BDNF\/TrkB\/CREB\/PI3K-Akt pathway, which offers a novel strategy for IVH treatment in preterm infants.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/stcltm\/szag086","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:48:47Z","timestamp":1790855327000},"source":"Crossref","is-referenced-by-count":0,"title":["Human umbilical cord mesenchymal stem cells alleviate brain injury and promote neuroregeneration via BDNF\/TrkB\/CREB\/PI3K-Akt pathway in preterm rats with intraventricular hemorrhage"],"prefix":"10.1093","volume":"15","author":[{"given":"Mingyou","family":"Yu","sequence":"first","affiliation":[{"name":"Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University , Guiyang 550000, Guizhou,","place":["China"]},{"name":"Department of Neonatology, Affiliated Hospital of Guizhou Medical University , Guiyang 550000, Guizhou,","place":["China"]},{"name":"Department of Neonatology, Tongren People\u2019s Hospital , Tongren 554300, Guizhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University , Guiyang 550000, Guizhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7565-2486","authenticated-orcid":false,"given":"Xuxian","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University , Guiyang 550000, Guizhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University , Guiyang 550000, Guizhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Hu","sequence":"additional","affiliation":[{"name":"Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University , Guiyang 550000, Guizhou,","place":["China"]},{"name":"Department of Neonatology, Affiliated Hospital of Guizhou Medical University , Guiyang 550000, Guizhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changge","family":"Wei","sequence":"additional","affiliation":[{"name":"Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University , Guiyang 550000, Guizhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Ran","sequence":"additional","affiliation":[{"name":"Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University , Guiyang 550000, Guizhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manni","family":"Cao","sequence":"additional","affiliation":[{"name":"Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University , Guiyang 550000, Guizhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University , Guiyang 550000, Guizhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueli","family":"Ding","sequence":"additional","affiliation":[{"name":"Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University , Guiyang 550000, Guizhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University , Guiyang 550000, Guizhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Liu","sequence":"additional","affiliation":[{"name":"Guizhou Guizhong Biotechnology Co., Ltd. , Guiyang 550000, Guizhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maoqiong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Affiliated Hospital of Guizhou Medical University , Guiyang 550000, Guizhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwei","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University , Guiyang 550000, Guizhou,","place":["China"]},{"name":"Department of Neonatology, Affiliated Hospital of Guizhou Medical University , Guiyang 550000, Guizhou,","place":["China"]},{"name":"Department of Pharmacology, School of Basic Medical Sciences, Guizhou Medical University , Guiyang 550000, Guizhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,16]]},"reference":[{"key":"2026101621570590900_szag086-B1","doi-asserted-by":"crossref","first-page":"151595","DOI":"10.1016\/j.semperi.2022.151595","article-title":"Cerebral gray matter injuries in infants with intraventricular hemorrhage","volume":"46","author":"Sharma","year":"2022","journal-title":"Semin Perinatol"},{"key":"2026101621570590900_szag086-B2","doi-asserted-by":"crossref","first-page":"114472","DOI":"10.1016\/j.expneurol.2023.114472","article-title":"Innate immune activation and white matter injury in a rat model of neonatal intraventricular hemorrhage are dependent on developmental stage","volume":"367","author":"Zamorano","year":"2023","journal-title":"Exp Neurol"},{"key":"2026101621570590900_szag086-B3","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1055\/s-0043-1770358","article-title":"Neuroendoscopic lavage and third ventriculostomy for the treatment of intraventricular hemorrhage and hydrocephalus in neonates. A prospective study with 18 months of follow-up","volume":"85","author":"Islas-Aguilar","year":"2024","journal-title":"J Neurol Surg A Cent Eur Neurosurg"},{"key":"2026101621570590900_szag086-B4","doi-asserted-by":"crossref","first-page":"e01756","DOI":"10.1002\/brb3.1756","article-title":"Efficacy and safety profile of neuroendoscopic hematoma evacuation combined with intraventricular lavage in severe intraventricular hemorrhage patients","volume":"10","author":"Ding","year":"2020","journal-title":"Brain Behav"},{"key":"2026101621570590900_szag086-B5","doi-asserted-by":"crossref","first-page":"101224","DOI":"10.1016\/j.siny.2021.101224","article-title":"Recovery of the brain after intraventricular hemorrhage","volume":"27","author":"Cheng","year":"2022","journal-title":"Semin Fetal Neonatal Med"},{"key":"2026101621570590900_szag086-B6","first-page":"Cd013201","article-title":"Stem cell-based interventions for the prevention and treatment of intraventricular haemorrhage and encephalopathy of prematurity in preterm infants","volume":"2","author":"Romantsik","year":"2023","journal-title":"Cochrane Database Syst Rev"},{"key":"2026101621570590900_szag086-B7","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1007\/s00381-024-06703-2","article-title":"The role of stem cells in the management of neonatal posthemorrhagic hydrocephalus","volume":"41","author":"Komiotis","year":"2024","journal-title":"Childs Nerv Syst"},{"key":"2026101621570590900_szag086-B8","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1093\/stmcls\/sxac062","article-title":"Mesenchymal stromal\/stem cell extracellular vesicles and perinatal injury: one formula for many diseases","volume":"40","author":"Delavogia","year":"2022","journal-title":"Stem Cells (Dayton, Ohio)"},{"key":"2026101621570590900_szag086-B9","first-page":"419","article-title":"Pathophysiology and clinical management of intraventricular hemorrhage and post-hemorrhagic hydrocephalus","volume":"50","author":"Yamamoto","year":"2022","journal-title":"No Shinkei Geka"},{"key":"2026101621570590900_szag086-B10","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.neuroscience.2025.03.007","article-title":"Histopathological and functional characterization of a neonatal mouse model of intraventricular hemorrhage","volume":"572","author":"Mishra","year":"2025","journal-title":"Neuroscience"},{"key":"2026101621570590900_szag086-B11","doi-asserted-by":"crossref","first-page":"115607","DOI":"10.1016\/j.expneurol.2025.115607","article-title":"Mechanism of human umbilical cord mesenchymal stem cells in the treatment of germinal matrix hemorrhage-intraventricular hemorrhage","volume":"398","author":"Xu","year":"2026","journal-title":"Exp Neurol"},{"key":"2026101621570590900_szag086-B12","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1159\/000505311","article-title":"Protective effects of transforming growth factor-\u03b21 knockdown in human umbilical cord mesenchymal stem cells against subarachnoid hemorrhage in a rat model","volume":"49","author":"Chen","year":"2020","journal-title":"Cerebrovascular Diseases (Basel, Switzerland)"},{"key":"2026101621570590900_szag086-B13","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1007\/s11064-024-04212-x","article-title":"Neuroprotection of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in alleviating ischemic stroke-induced brain injury by regulating inflammation and oxidative stress","volume":"49","author":"Liu","year":"2024","journal-title":"Neurochem Res"},{"key":"2026101621570590900_szag086-B14","doi-asserted-by":"crossref","first-page":"1323678","DOI":"10.3389\/fcell.2023.1323678","article-title":"Cellular microenvironment: a key for tuning mesenchymal stem cell senescence","volume":"11","author":"Sun","year":"2023","journal-title":"Front Cell Dev Biol"},{"key":"2026101621570590900_szag086-B15","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41423-023-01034-9","article-title":"Mesenchymal stem\/stromal cells (MSCs): origin, immune regulation, and clinical applications","volume":"20","author":"Zhou","year":"2023","journal-title":"Cell Mol Immunol"},{"key":"2026101621570590900_szag086-B16","doi-asserted-by":"crossref","first-page":"109633","DOI":"10.1016\/j.neuropharm.2023.109633","article-title":"HDAC3 inhibitor (BRD3308) modulates microglial pyroptosis and neuroinflammation through PPAR\u03b3\/NLRP3\/GSDMD to improve neurological function after intraventricular hemorrhage in mice","volume":"237","author":"Li","year":"2023","journal-title":"Neuropharmacology"},{"key":"2026101621570590900_szag086-B17","doi-asserted-by":"crossref","first-page":"149321","DOI":"10.1016\/j.bbrc.2023.149321","article-title":"HGF secreted by hUC-MSCs mitigates neuronal apoptosis to repair the injured spinal cord via phosphorylation of Akt\/FoxO3a pathway","volume":"692","author":"Cai","year":"2024","journal-title":"Biochem Biophys Res Commun"},{"key":"2026101621570590900_szag086-B18","doi-asserted-by":"crossref","first-page":"3021750","DOI":"10.1155\/2020\/3021750","article-title":"Ultrashort wave combined with human umbilical cord mesenchymal stem cell (HUC-MSC) transplantation inhibits NLRP3 inflammasome and improves spinal cord injury via MK2\/TTP signalling pathway","volume":"2020","author":"Na","year":"2020","journal-title":"Biomed Res Int"},{"key":"2026101621570590900_szag086-B19","doi-asserted-by":"crossref","DOI":"10.3390\/brainsci12050631","article-title":"Preconditioned MSCs alleviate cerebral ischemia-reperfusion injury in rats by improving the neurological function and the inhibition of apoptosis","volume":"12","author":"Zheng","year":"2022","journal-title":"Brain Sci"},{"key":"2026101621570590900_szag086-B20","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.freeradbiomed.2025.02.045","article-title":"Human umbilical cord-derived mesenchymal stem cells attenuate liver fibrosis by inhibiting hepatocyte ferroptosis through mitochondrial transfer","volume":"231","author":"Xiong","year":"2025","journal-title":"Free Radic Biol Med"},{"key":"2026101621570590900_szag086-B21","doi-asserted-by":"crossref","first-page":"911","DOI":"10.17219\/acem\/192773","article-title":"Human umbilical cord mesenchymal stem cell-derived exosomes combined with mouse nerve growth factor can more effectively ameliorate the motor disorder and brain pathological injury in mice with cerebral palsy","volume":"34","author":"Chen","year":"2025","journal-title":"Adv Clin Exp Med"},{"key":"2026101621570590900_szag086-B22","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41536-024-00349-z","article-title":"hUC-MSCs-derived MFGE8 ameliorates locomotor dysfunction via inhibition of ITGB3\/ NF-\u03baB signaling in an NMO mouse model","volume":"9","author":"Xu","year":"2024","journal-title":"NPJ Regen Med"},{"key":"2026101621570590900_szag086-B23","doi-asserted-by":"crossref","first-page":"483","DOI":"10.21037\/atm-22-1578","article-title":"Effect of acellular nerve scaffold containing human umbilical cord-derived mesenchymal stem cells on nerve repair and regeneration in rats with sciatic nerve defect","volume":"10","author":"Qian","year":"2022","journal-title":"Ann Transl Med"},{"key":"2026101621570590900_szag086-B24","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.131355","article-title":"STAT6\/Arg1 promotes microglia\/macrophage efferocytosis and inflammation resolution in stroke mice","volume":"4","author":"Cai","year":"2019","journal-title":"JCI Insight"},{"key":"2026101621570590900_szag086-B25","doi-asserted-by":"crossref","first-page":"117400","DOI":"10.1016\/j.jep.2023.117400","article-title":"Periplaneta americana (L.) extract activates the ERK\/CREB\/BDNF pathway to promote post-stroke neuroregeneration and recovery of neurological functions in rats","volume":"321","author":"Rao","year":"2024","journal-title":"J Ethnopharmacol"},{"key":"2026101621570590900_szag086-B26","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1186\/s13287-023-03499-x","article-title":"Human umbilical cord-derived mesenchymal stem cells ameliorate perioperative neurocognitive disorder by inhibiting inflammatory responses and activating BDNF\/TrkB\/CREB signaling pathway in aged mice","volume":"14","author":"Wei","year":"2023","journal-title":"Stem Cell Res Ther"},{"key":"2026101621570590900_szag086-B27","doi-asserted-by":"crossref","first-page":"122282","DOI":"10.1016\/j.lfs.2023.122282","article-title":"TrkB\/BDNF signaling pathway and its small molecular agonists in CNS injury","volume":"336","author":"Wang","year":"2024","journal-title":"Life Sci"},{"key":"2026101621570590900_szag086-B28","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1007\/s12035-024-04357-4","article-title":"BDNF-TrkB signaling in mitochondria: implications for neurodegenerative diseases","volume":"62","author":"Ks","year":"2025","journal-title":"Mol Neurobiol"},{"key":"2026101621570590900_szag086-B29","doi-asserted-by":"crossref","first-page":"113881","DOI":"10.1016\/j.biopha.2022.113881","article-title":"The role of PI3K\/Akt signalling pathway in spinal cord injury","volume":"156","author":"Xiao","year":"2022","journal-title":"Biomed Pharmacother"}],"container-title":["Stem Cells Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/15\/11\/szag086\/72052507\/szag086.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/15\/11\/szag086\/72052507\/szag086.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:57:15Z","timestamp":1792202235000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stcltm\/article\/doi\/10.1093\/stcltm\/szag086\/8931813"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,16]]},"references-count":29,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,10,16]]}},"URL":"https:\/\/doi.org\/10.1093\/stcltm\/szag086","relation":{},"ISSN":["2157-6564","2157-6580"],"issn-type":[{"value":"2157-6564","type":"print"},{"value":"2157-6580","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,11]]},"published":{"date-parts":[[2026,10,16]]},"article-number":"szag086"}}