Ureaplasma-Driven Neonatal Neuroinflammation: Novel Insights from an Ovine Model.
Christine SilwedelMatthias Christian HüttenChristian P SpeerChristoph HärtelAxel HaarmannBirgit HenrichMaud P M TijssenAbdullah Ahmed AlnakhliOwen B SpillerNicolas SchlegelSilvia SeidenspinnerBoris W KramerKirsten GlaserPublished in: Cellular and molecular neurobiology (2022)
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.
Keyphrases
- white matter
- cerebrospinal fluid
- cerebral ischemia
- preterm birth
- cell death
- binding protein
- real time pcr
- poor prognosis
- subarachnoid hemorrhage
- traumatic brain injury
- low birth weight
- lipopolysaccharide induced
- multiple sclerosis
- blood brain barrier
- lps induced
- cognitive impairment
- resting state
- computed tomography
- brain injury
- big data
- weight gain
- long non coding rna
- inflammatory response
- magnetic resonance
- oxidative stress
- contrast enhanced
- single molecule
- preterm infants
- induced apoptosis
- molecular dynamics simulations
- drug induced
- cell migration
- small molecule
- artificial intelligence
- high glucose
- cell cycle arrest
- young adults
- sensitive detection
- mesenchymal stem cells
- amino acid
- pregnancy outcomes
- diffusion weighted imaging