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Ureaplasma-driven neonatal neuroinflammation: novel insights from an ovine model

Silwedel, Christine, Hütten, Matthias C., Speer, Christian P., Härtel, Christoph, Haarmann, Axel, Henrich, Birgit, Tijssen, Maud P. M., Alnakhli, Abdullah Ahmed, Spiller, Owen B., Schlegel, Nicolas, Seidenspinner, Silvia, Kramer, Boris W. and Glaser, Kirsten 2022. Ureaplasma-driven neonatal neuroinflammation: novel insights from an ovine model. Cellular and Molecular Neurobiology 10.1007/s10571-022-01213-8

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Abstract

Ureaplasma species (spp.) are considered commensals of the adult genitourinary tract, but have been associated with chorioamnionitis, preterm birth, and invasive infections in neonates, including meningitis. Data on mechanisms involved in Ureaplasma-driven neuroinflammation are scarce. The present study addressed brain inflammatory responses in preterm lambs exposed to Ureaplasma parvum (UP) in utero. 7 days after intra-amniotic injection of UP (n = 10) or saline (n = 11), lambs were surgically delivered at gestational day 128–129. 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 ureB-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–X–C 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 Ureaplasma-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–brain barrier function. According to these data and previous in vitro findings from our group, we speculate that Ureaplasma-induced caspase and receptor responses affect CNS barrier properties and thus facilitate neuroinflammation.

Item Type: Article
Date Type: Publication
Status: In Press
Schools: Medicine
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher: Springer
ISSN: 0272-4340
Date of First Compliant Deposit: 25 March 2022
Date of Acceptance: 14 March 2022
Last Modified: 30 Mar 2022 09:45
URI: https://orca.cardiff.ac.uk/id/eprint/148647

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