{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:16:47Z","timestamp":1791400607778,"version":"4.3.3"},"reference-count":34,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,5,17]],"date-time":"2019-05-17T00:00:00Z","timestamp":1558051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012256","name":"Cerebral Palsy Alliance Research Foundation","doi-asserted-by":"publisher","award":["PG07917"],"award-info":[{"award-number":["PG07917"]}],"id":[{"id":"10.13039\/100012256","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cerebral palsy (CP) is a permanent motor disorder that results from brain injury and neuroinflammation during the perinatal period. Mesenchymal stromal cells (MSCs) have been explored as a therapy in multiple adult neuroinflammatory conditions. Our study examined the therapeutic benefits of intranasal delivery of human umbilical cord tissue (UC) derived-MSCs in a rat model of neonatal hypoxic\u2013ischemic (HI) brain injury. To do this, HI was performed on postnatal day 10 Sprague-Dawley rat pups via permanent ligation of the left carotid artery, followed by a hypoxic challenge of 8% oxygen for 90 min. A total of 200,000 UC-MSCs (10 million\/kg) were administered intranasally 24 h post-HI. Motor control was assessed after seven days, followed by post-mortem. Analysis included brain immunohistochemistry, gene analysis and serum cytokine measurement. Neonatal HI resulted in brain injury with significant loss of neurons, particularly in the hippocampus. Intranasal administration of UC-MSCs significantly reduced the loss of brain tissue and increased the number of hippocampal neurons. HI significantly upregulated brain inflammation and expression of pro-inflammatory cytokines, while intranasal UC-MSCs significantly reduced markers of neuroinflammation. This study demonstrated that a clinically relevant dose (10 million\/kg) of UC-MSCs was neuroprotective following HI by restoring neuronal cell numbers and reducing brain inflammation. Therefore, intranasal delivery of UC-MSCs may be an effective therapy for neonatal brain injury.<\/jats:p>","DOI":"10.3390\/ijms20102449","type":"journal-article","created":{"date-parts":[[2019,5,17]],"date-time":"2019-05-17T11:06:46Z","timestamp":1558091206000},"page":"2449","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Intranasal Delivery of Mesenchymal Stromal Cells Protects against Neonatal Hypoxic\u2013Ischemic Brain Injury"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8421-461X","authenticated-orcid":false,"given":"Courtney A.","family":"McDonald","sequence":"first","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Clayton 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6031-9035","authenticated-orcid":false,"given":"Zlatikha","family":"Djuliannisaa","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Clayton 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Petraki","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Clayton 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2780-1193","authenticated-orcid":false,"given":"Madison C. B.","family":"Paton","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Clayton 3168, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tayla R.","family":"Penny","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Clayton 3168, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy E.","family":"Sutherland","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Clayton 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margie","family":"Castillo-Melendez","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Clayton 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iona","family":"Novak","sequence":"additional","affiliation":[{"name":"Cerebral Palsy Alliance Research Institute, University of Sydney, Camperdown 2086, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham","family":"Jenkin","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Clayton 3168, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Fahey","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Monash University, Clayton 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne L.","family":"Miller","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Clayton 3168, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.ridd.2011.12.001","article-title":"Medical expenditures attributable to cerebral palsy and intellectual disability among Medicaid-enrolled children","volume":"33","author":"Kancherla","year":"2012","journal-title":"Res. 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