Chorioamnionitis in Rats Precipitates Extended Postnatal Inflammatory Lymphocyte Hyperreactivity

Area of Science:

• Neuroscience
• Immunology
• Developmental Biology

Background:

• Preterm birth is a major cause of perinatal brain injury (PBI).
• In utero inflammation, such as chorioamnionitis (CHORIO), and placental insufficiency contribute to PBI.
• Altered immune responses are observed in preterm infants with cerebral palsy (CP).

Purpose of the Study:

• To investigate if peripheral immune responses are altered in a rat model of CP induced by in utero inflammation.
• To determine if peripheral blood mononuclear cells (PBMCs) exhibit hyperresponsiveness to inflammatory stimuli postnatally.

Main Methods:

• A rat model was established using lipopolysaccharide (LPS) and uterine artery occlusion to simulate in utero injury.
• PBMCs were isolated from pups at postnatal days 7 (P7) and P21.
• PBMCs were stimulated with LPS in vitro, and inflammatory profiles and cell composition were analyzed using multiplex immunoassays and flow cytometry (FC).

Main Results:

• CHORIO-exposed PBMCs showed hyperreactivity, secreting significantly more tumor necrosis factor α (TNFα) and C-X-C chemokine ligand 1 at P7.
• FC confirmed increased intracellular TNFα and myeloid cells in CHORIO pups post-LPS stimulation at P7.
• Sustained TNFα secretion until P21, with increased interleukin 6 and integrin β1 expression, indicated persistent immune hyperreactivity.

Conclusions:

• In utero injury primes the peripheral immune system, leading to augmented inflammatory signaling.
• Primed peripheral immune cells may exacerbate PBI and increase susceptibility to chronic neurological disease.
• Understanding these inflammatory mechanisms could lead to biomarkers and individualized treatments for PBI.