Transfusion of Old RBCs Induces Neuroinflammation and Cognitive Impairment

Abstract

Objectives Transfusing red blood cells (RBC) stored for longer than 14 days (old RBC) in humans is common. This transfusion can injure organs, such as lungs and kidneys. We determined whether transfusion with old RBC injured brain. Design Prospective, controlled, animal study Setting University research laboratory Subjects Adult male Sprague–Dawley rats Interventions Six-month old Sprague–Dawley rats lost 20% total blood volume and then received RBC prepared from equal volume of the lost blood. RBC was stored for 1 day (fresh RBC) or 7 days (old RBC, storage lesions similar to those of human RBC stored for 28 days). Some rats received intravenous cell-free hemoglobin. These rats were not subjected to hemorrhage and RBC transfusion. Measurements and Main Results Rats were subjected to Barnes maze and fear conditioning tests from one week after blood transfusion. Rats transfused with old RBC but not fresh RBC took a longer time to identify the target hole in the Barnes maze and had less context-related fear conditioning behavior than control rats. Old RBC significantly increased interleukin 6 and ionized calcium-binding adapter molecule 1 in the hippocampus at 24 h after the transfusion. These effects were attenuated by sulforaphane and minocycline, an antibiotic with anti-inflammatory property. Old RBC solution had a higher concentration of cell-free hemoglobin. Sulforaphane increased haptoglobin, a chelator of cell-free hemoglobin. Rats received cell-free hemoglobin had a pattern of neuroinflammation and impairment of learning and memory similar to that of rats received old RBC. Conclusions These results provide initial evidence to suggest that transfusion of old RBC induces neuroinflammation and impairment of learning and memory. These effects may be mediated by cell-free hemoglobin.

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