Transfusion. 2025 Dec 3. doi: 10.1111/trf.70018. Online ahead of print.
ABSTRACT
BACKGROUND: Red blood cell transfusions (RBCT) are essential and lifesaving for preterm infants who suffer from physiological and iatrogenic anemia. Phlebotomy-induced anemia (PIA) in neonatal murine pups has been linked to hippocampal inflammation; however, the impact of repletion with packed RBCT has not been evaluated despite its known advantages in relieving anemia and restoring oxygen-carrying capacity.
STUDY DESIGN AND METHODS: C57BL/6 pups underwent PIA, and FVB-donor-derived packed RBCs were administered retro-orbitally on postnatal(P) day 11. On P12, whole-brain protein lysate was analyzed for cytokines and chemokines using a Multiplex array. Endotoxin was measured using the LAL test. Immunofluorescence and flow cytometry were performed to characterize microglia and recruited myeloid cells. The key inflammatory functional genes were measured by qRT-PCR.
RESULTS: Inflammatory cytokines and chemokines were significantly elevated in the anemic brains compared to naïve controls and markedly higher in anemic-transfused brains compared to transfused controls, resulting in anemia-transfusion-associated brain inflammation (ATBI). Anemic and anemic-transfused mouse groups had increased BBB permeability, and brain tissue had elevated levels of endotoxin with a loss of ramified-structured microglia. ATBI was associated with the recruitment of CD11bhiCD45+Ly6C+ monocytes in the brains of anemic-transfused pups and showed a hyperinflammatory phenotype compared to tissue-resident microglial cells (CD45–CD11bhi) and revealed suppression of genes involved in myelination, neuronal cell proliferation, and developmental processes.
CONCLUSION: We report that PIA causes early brain inflammation and RBCT leads to the recruitment of circulating monocytes to the anemic brain, thus contributing to a chronic hyperinflammatory response with transcriptional changes in genes associated with brain function.
PMID:41334989 | DOI:10.1111/trf.70018
