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This study aimed to elucidate the role of IL-8 in the therapeutic effects of hUCBCs in a mouse model of hypoxic-ischaemic brain injury (HI). In P7 HI mouse brains, hUCBC administration at day 7 after HI upregulated the gene expression of Cxcl2, the mouse IL-8 homologue and increased the expression of its receptor, CXCR2. hUCBC administration restored the sequential downstream signalling axis of p-p38\/p-MAPKAPK2, NF\u03baB, and angiogenic factors, which were downregulated by HI. An<jats:italic>in vitro<\/jats:italic>assay revealed the downregulation of the angiogenic pathway by CXCR2 knockdown and p38 inhibition.<jats:italic>In vivo<\/jats:italic>p38 inhibition prior to hUCBC administration in HI mouse brains produced identical results. Behavioural outcomes revealed a therapeutic effect (<jats:italic>ps<\/jats:italic>\u2009&lt;\u20090.01) of hUCBC or IL-8 administration, which was correlated with decreases in infarct size and angiogenic findings in the striatum. In conclusion, the response of the host to hUCBC administration in mice upregulated Cxcl2, which led to the activation of the IL-8-mediated p-p38 signalling pathway. The upregulation of the downstream pathway and angiogenic growth factors via NF\u03baB can be inferred to be the potential therapeutic mechanism of hUCBCs.<\/jats:p>","DOI":"10.1038\/s41598-020-61441-0","type":"journal-article","created":{"date-parts":[[2020,3,10]],"date-time":"2020-03-10T11:03:11Z","timestamp":1583838191000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Therapeutic mechanism of cord blood mononuclear cells via the IL-8-mediated angiogenic pathway in neonatal hypoxic-ischaemic brain injury"],"prefix":"10.1038","volume":"10","author":[{"given":"Kye Hee","family":"Cho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jee In","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Ock","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Eun","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Wook","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MinYoung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,10]]},"reference":[{"key":"61441_CR1","first-page":"1","volume":"49","author":"P Baxter","year":"2007","unstructured":"Baxter, P. et al. 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