Ureaplasma-Driven Neonatal Neuroinflammation : Novel Insights from an Ovine Model

© 2022. The Author(s)..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:43

Enthalten in:

Cellular and molecular neurobiology - 43(2023), 2 vom: 25. März, Seite 785-795

Sprache:

Englisch

Beteiligte Personen:

Silwedel, Christine [VerfasserIn]
Hütten, Matthias C [VerfasserIn]
Speer, Christian P [VerfasserIn]
Härtel, Christoph [VerfasserIn]
Haarmann, Axel [VerfasserIn]
Henrich, Birgit [VerfasserIn]
Tijssen, Maud P M [VerfasserIn]
Alnakhli, Abdullah Ahmed [VerfasserIn]
Spiller, Owen B [VerfasserIn]
Schlegel, Nicolas [VerfasserIn]
Seidenspinner, Silvia [VerfasserIn]
Kramer, Boris W [VerfasserIn]
Glaser, Kirsten [VerfasserIn]

Links:

Volltext

Themen:

Animal model
CNS Integrity
Caspases
EC 3.4.22.-
Immaturity
Journal Article
Neonatal meningitis
Preterm birth
Ureaplasma parvum

Anmerkungen:

Date Completed 28.02.2023

Date Revised 28.02.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1007/s10571-022-01213-8

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM338642579