Liver-gut axis in neonatal anemia and its role in transfusion associated with gut mucosal injury
Anemia is a nearly universal diagnosis in preterm infants and is associated with increased morbidity and mortality worldwide. When severe enough to be treated with RBC transfusion, critical adverse effects can be seen; one such consequence is necrotizing enterocolitis (NEC), an inflammatory bowel necrosis of preterm infants characterized by monocyte infiltration and activation. In this project, Dr. Krishnan’s team investigating the ontogeny of implicated monocytes, the mechanism(s) involved in their recruitment, and potential strategies to prevent their activation in the progression to NEC.
RBC transfusion exacerbates brain inflammation in anemic murine neonates and causes long term neurodevelopment impairment
Preterm neonates comprise one of the most heavily transfused populations, as 50-94% of very low birth weight (VLBW) infants receive at least one RBC transfusion during their stay in the neonatal intensive care unit (NICU) to correct anemia, which is associated with increased morbidity and mortality worldwide. Though repletion with packed RBC transfusion has obvious benefits, transfusion in the setting of severe anemia has also been implicated in the subsequent development of necrotizing enterocolitis (NEC) and impaired neurocognitive outcomes. In this project, the investigator proposes sequential studies to investigate the role of anemia and/or RBC transfusion in anemic-transfused brain inflammation (ATBI), the mechanism(s) of NEC-causing monocytes in ATBI, and potential strategies to prevent their inflammation in the progression to ATBI.
RBC transfusion in anemic neonates leads to systemic inflammatory response syndrome
Transfusions of Red Blood Cells (RBCT) are necessary and lifesaving in premature and critically ill infants, who experience severe anemia due to both physiologic and iatrogenic factors. The risks of experiencing severe anemia during critical developmental periods must be balanced with the risks of transfusions, which can lead to Systemic Inflammatory Response Syndrome (SIRS) and potentially Multi Organ Dysfunction Syndrome (MODS). In this project, we design sequential studies to investigate the mechanisms and potential strategies to prevent SIRS in neonatal infants during severe anemia and transfusion by using a well-established preclinical mouse model.
Effect of Platelet Transfusions on Neonatal Intestinal Injury
Thrombocytopenia and platelet activation are well-documented hematological abnormalities in infants with necrotizing enterocolitis (NEC), which is an inflammatory bowel necrosis of premature infants and is a leading cause of mortality in neonates born at <32 week’s gestation. This project generates important insights into the role of activated platelets in the development of gut mucosal injury, and the relative contribution of changes in platelet conformation and the release of granule contents that occur during the process of activation. These studies will also inform about the mechanisms of platelet production, activation, development of platelet-monocyte aggregates, role of microparticles, and the role of platelet-derived inflammatory mediators during NEC.