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Modeling Ascending Vaginal Infection, Preterm Birth, and Neonatal Morbidity in Mice
Published on: October 10, 2025
A Critical Review of Models of Perinatal Infection
Justin M Dean1, Zhongjie Shi, Bobbi Fleiss
1Department of Physiology, University of Auckland, Auckland, New Zealand.
Insights
Preterm infants face poor neurodevelopmental outcomes, potentially linked to fetal and early postnatal infection and inflammation. Understanding these inflammatory responses is key to developing neuroprotective strategies.
Area of Science:
- Perinatology
- Neuroscience
- Immunology
Background:
- Preterm infants exhibit poor long-term neurodevelopmental, cognitive, and learning outcomes.
- Severe brain injury is now uncommon in these infants, suggesting other factors contribute to disability.
- Clinical evidence points to infection and inflammation during fetal and early postnatal life as potential underlying causes.
Purpose of the Study:
- To review experimental evidence linking infection/inflammation with perinatal brain injury.
- To explore experimental determinants such as microglia response and immune maturity.
- To emphasize the role of lipopolysaccharide (LPS) and its origin.
Main Methods:
- Review of experimental studies on acute and chronic infection/inflammation in perinatal brain injury models.
- Analysis of factors influencing the brain's response to infection, including microglia activation.
- Examination of the impact of exposure patterns and specific inflammatory triggers like lipopolysaccharide.
Main Results:
- Experimental evidence supports a link between infection/inflammation and perinatal brain injury.
- Microglia response, brain/immune maturity, and exposure patterns are critical determinants.
- The origin and structure of lipopolysaccharide are important considerations in the inflammatory cascade.
Conclusions:
- Infection and inflammation are significant contributors to poor neurodevelopmental outcomes in preterm infants.
- Understanding the precise inflammatory reaction timeline is crucial.
- Targeted neuroprotective strategies are needed to safeguard the perinatal brain from inflammatory damage.
Abstract:
One of the central, unanswered questions in perinatology is why preterm infants continue to have such poor long-term neurodevelopmental, cognitive and learning outcomes, even though severe brain injury is now rare. There is now strong clinical evidence that one factor underlying disability may be infection, as well as nonspecific inflammation, during fetal and early postnatal life. In this review, we examine the experimental evidence linking both acute and chronic infection/inflammation with perinatal brain injury and consider key experimental determinants, including the microglia response, relative brain and immune maturity and the pattern of exposure to infection. We highlight the importance of the origin and derivation of the bacterial cell wall component lipopolysaccharide. Such experimental paradigms are essential to determine the precise time course of the inflammatory reaction and to design targeted neuroprotective strategies to protect the perinatal brain from infection and inflammation.
