Necrotizing enterocolitis is associated with acute brain responses in preterm pigs

Area of Science:

• Neonatal research
• Neuroscience
• Gastroenterology

Background:

• Necrotizing enterocolitis (NEC) is a severe intestinal inflammatory condition in preterm infants.
• Infants surviving NEC often exhibit impaired neurodevelopmental outcomes.
• The link between NEC and neurodevelopment is poorly understood, potentially involving brain inflammation.

Purpose of the Study:

• To investigate the acute effects of intestinal NEC lesions on the developing hippocampus in preterm pigs.
• To explore the association between NEC severity and hippocampal gene expression, neuroinflammation, and neural plasticity.

Main Methods:

• Preterm pigs were used as a model for human infants with NEC.
• Researchers analyzed neonatal arousal, physical activity, and cerebrospinal fluid (CSF) effects.
• Hippocampal transcriptome analysis, qPCR, and microglia activation quantification were performed.

Main Results:

• NEC rapidly reduced physical activity, particularly with small intestine lesions.
• Significant changes in hippocampal gene expression related to neuroinflammation and hypoxia were observed in NEC pigs.
• CSF from NEC pigs promoted neurite outgrowth in vitro, mediated by S100A8/S100A9 proteins.

Conclusions:

• Intestinal NEC lesions, especially in the small intestine, alter hippocampal gene expression, potentially driving neuroinflammation and affecting neural circuit formation.
• These findings suggest a mechanism linking gut inflammation to brain development.
• Early brain-protective interventions are recommended for preterm infants with NEC to mitigate neurological deficits.