Fiona M O'Hare1, William Watson2, Amanda O'Neill2, Tim Grant2, Chike Onwuneme1, Veronica Donoghue3, Eoghan Mooney4, Paul Downey4, John Murphy5, Anne Twomey5, Eleanor J Molloy6. 1. 1] Department of Paediatrics, National Maternity Hospital, Dublin 2, Ireland [2] University College Dublin School of Medicine and Medical Sciences, Dublin, Ireland [3] University College Dublin Conway Institute of Biomolecular and Biomedical Sciences, Dublin, Ireland [4] National Children's Research Centre, Dublin, Ireland. 2. 1] University College Dublin School of Medicine and Medical Sciences, Dublin, Ireland [2] University College Dublin Conway Institute of Biomolecular and Biomedical Sciences, Dublin, Ireland. 3. 1] Department of Paediatrics, National Maternity Hospital, Dublin 2, Ireland [2] Department of Radiology, Children's University Hospital, Dublin, Ireland. 4. Department of Pathology, National Maternity Hospital, Dublin 2, Ireland. 5. Department of Paediatrics, National Maternity Hospital, Dublin 2, Ireland. 6. 1] Department of Paediatrics, National Maternity Hospital, Dublin 2, Ireland [2] University College Dublin School of Medicine and Medical Sciences, Dublin, Ireland [3] University College Dublin Conway Institute of Biomolecular and Biomedical Sciences, Dublin, Ireland [4] Department of Neonatology, Our Lady's Children's Hospital, Dublin, Ireland [5] Department of Paediatrics, Royal College of Surgeons in Ireland, Dublin, Ireland [6] Department of Paediatrics, Trinity College Dublin, University of Dublin, Dublin, Ireland.
Abstract
BACKGROUND: Activated leukocytes and infection are implicated in neonatal brain injury. Leukocyte surface receptors are increased in stroke models and may be targets for future adjunctive therapies. METHODS: Serial blood samples were analyzed from preterm infants (n = 51; <32 wk gestation) on days 0, 1, 2, and 7 of life. Monocyte and neutrophil activation were evaluated via flow cytometry at baseline and following endotoxin stimulation ex vivo by measuring CD11b (activation), toll-like receptor 4 (TLR-4; endotoxin recognition) expression, and intracellular reactive oxygen intermediate (ROI) production (function). RESULTS: Control preterm infants with normal neuroimaging had elevated baseline CD11b and TLR-4 expression and ROI production compared with adults as well as a robust immune response following endotoxin stimulation. Preterm infants with abnormal neuroimaging had increased neutrophil TLR-4 and ROI compared with all controls. CONCLUSION: Preterm infants have a robust immune response compared with adults. Increased TLR-4 expression in preterm infants with abnormal neuroimaging is similar to findings in adult stroke. In addition, ROI production may cause tissue injury. The modulation of these responses may be beneficial in preterm inflammatory disorders.
BACKGROUND: Activated leukocytes and infection are implicated in neonatal brain injury. Leukocyte surface receptors are increased in stroke models and may be targets for future adjunctive therapies. METHODS: Serial blood samples were analyzed from preterm infants (n = 51; <32 wk gestation) on days 0, 1, 2, and 7 of life. Monocyte and neutrophil activation were evaluated via flow cytometry at baseline and following endotoxin stimulation ex vivo by measuring CD11b (activation), toll-like receptor 4 (TLR-4; endotoxin recognition) expression, and intracellular reactive oxygen intermediate (ROI) production (function). RESULTS: Control preterm infants with normal neuroimaging had elevated baseline CD11b and TLR-4 expression and ROI production compared with adults as well as a robust immune response following endotoxin stimulation. Preterm infants with abnormal neuroimaging had increased neutrophil TLR-4 and ROI compared with all controls. CONCLUSION: Preterm infants have a robust immune response compared with adults. Increased TLR-4 expression in preterm infants with abnormal neuroimaging is similar to findings in adult stroke. In addition, ROI production may cause tissue injury. The modulation of these responses may be beneficial in preterm inflammatory disorders.
Authors: Hassan O Eliwan; William R G Watson; Irene Regan; Brian Philbin; Fiona M O'Hare; Tammy Strickland; Amanda O'Neill; Michelle O'Rourke; Alfonso Blanco; Martina Healy; Beatrice Nolan; Owen Smith; Eleanor J Molloy Journal: Front Pediatr Date: 2019-09-27 Impact factor: 3.418
Authors: Yuma Kitase; Eric M Chin; Sindhu Ramachandra; Christopher Burkhardt; Nethra K Madurai; Colleen Lenz; Alexander H Hoon; Shenandoah Robinson; Lauren L Jantzie Journal: J Neuroinflammation Date: 2021-10-19 Impact factor: 8.322