Neuropathological and behavioral consequences of systemic LPS-induced infection in preterm mice: insights into neuroimmune interactions
Neonatal sepsis is a significant cause of neonatal death and brain injury, but the characteristics of neuroimmune changes caused by infection remain unclear. This study aimed to clarify the neuropathological and behavioral consequences of systemic LPS-induced sepsis in neonatal mice, with a focus on the neuroimmune interactions that contribute to brain injury. We found that LPS exposure in early life leads to long-term behavioral and developmental disorders, as evidenced by anxiety-like behaviors and impairments in social interactions. Transcriptome profiling of microglial cells after LPS exposure revealed critical changes, including the downregulation of homeostatic genes and a decrease in CD11c+ expression. Extensive neutrophil infiltration into the brain and the formation of neutrophil extracellular traps were observed, and these events might play significant roles in LPS-induced brain injury in preterm models. In support of this, we documented the dynamic shifts in chemokine expression in the brain, and this suggests a potential therapeutic target for modulating neutrophil infiltration. In addition, we used RNA-seq and Olink proteomics analysis on blood samples from preterm infants with sepsis to further validate the significant role of neutrophils. In conclusion, our study highlights the activation of microglia and the infiltration of neutrophils into the brain in our LPS-induced sepsis brain injury model, leading to abnormal white matter development and persistent behavioral changes. These insights offer a more comprehensive understanding of the impact of bacterial infections on the developing brain in preterm infants and suggest avenues for therapeutic interventions to reduce infection-induced brain injury.