Ureaplasma-Driven Neonatal Neuroinflammation: Novel Insights from an Ovine Model
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...
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Published in | Cellular and molecular neurobiology Vol. 43; no. 2; pp. 785 - 795 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Springer US
01.03.2023
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | 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
ure
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–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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0272-4340 1573-6830 |
DOI: | 10.1007/s10571-022-01213-8 |