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Data on mechanisms involved in <jats:italic>Ureaplasma<\/jats:italic>-driven neuroinflammation are scarce. The present study addressed brain inflammatory responses in preterm lambs exposed to <jats:italic>Ureaplasma parvum<\/jats:italic> (UP) in utero. 7\u00a0days after intra-amniotic injection of UP (<jats:italic>n<\/jats:italic>\u2009=\u200910) or saline (<jats:italic>n<\/jats:italic>\u2009=\u200911), lambs were surgically delivered at gestational day 128\u2013129. Expression of inflammatory markers was assessed in different brain regions using qRT-PCR and in cerebrospinal fluid (CSF) by multiplex immunoassay. CSF was analyzed for UP presence using <jats:italic>ure<\/jats:italic>B-based real-time PCR, and MRI scans documented cerebral white matter area and cortical folding. Cerebral tissue levels of atypical chemokine receptor (ACKR) 3, caspases 1-like, 2, 7, and C\u2013X\u2013C chemokine receptor (CXCR) 4 mRNA, as well as CSF interleukin-8 protein concentrations were significantly increased in UP-exposed lambs. UP presence in CSF was confirmed in one animal. Cortical folding and white matter area did not differ among groups. The present study confirms a role of caspases and the transmembrane receptors ACKR3 and CXCR4 in <jats:italic>Ureaplasma<\/jats:italic>-driven neuroinflammation. Enhanced caspase 1-like, 2, and 7 expression may reflect cell death. Increased ACKR3 and CXCR4 expression has been associated with inflammatory central nervous system (CNS) diseases and impaired blood\u2013brain barrier function. According to these data and previous in vitro findings from our group, we speculate that <jats:italic>Ureaplasma<\/jats:italic>-induced caspase and receptor responses affect CNS barrier properties and thus facilitate neuroinflammation.<\/jats:p>","DOI":"10.1007\/s10571-022-01213-8","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T09:03:02Z","timestamp":1648198982000},"page":"785-795","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Ureaplasma-Driven Neonatal Neuroinflammation: Novel Insights from an Ovine Model"],"prefix":"10.1007","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9678-326X","authenticated-orcid":false,"given":"Christine","family":"Silwedel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4870-5782","authenticated-orcid":false,"given":"Matthias C.","family":"H\u00fctten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian P.","family":"Speer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2181-7322","authenticated-orcid":false,"given":"Christoph","family":"H\u00e4rtel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5597-6225","authenticated-orcid":false,"given":"Axel","family":"Haarmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0565-5773","authenticated-orcid":false,"given":"Birgit","family":"Henrich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7071-0329","authenticated-orcid":false,"given":"Maud P. 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