title: Transfusion of Old RBCs Induces Neuroinflammation and Cognitive Impairment.
abstract: OBJECTIVE
  Transfusing RBCs 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.
  
  
  METHODS
  Prospective, controlled animal study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Adult male Sprague-Dawley rats.
  
  
  METHODS
  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 d). Some rats received IV cell-free hemoglobin. These rats were not subjected to hemorrhage and RBC transfusion.
  
  
  RESULTS
  Rats were subjected to Barnes maze and fear conditioning tests from 1 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 hours 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 that received cell-free hemoglobin had a pattern of neuroinflammation and impairment of learning and memory similar to that of rats that 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.
authors: 1Department of Anesthesiology, University of Virginia, Charlottesville, VA. 2Department of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China. 3Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China. 4Department of Anesthesiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. 5Department of Anesthesiology, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors: Hongying
authors: H
authors: Tan
authors: Jiangjiang
authors: J
authors: Bi
authors: Yunzhen
authors: Y
authors: Wang
authors: Junfeng
authors: J
authors: Zhang
authors: Zhiyi
authors: Z
authors: Zuo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000032:analysis; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology*; D003072:Cognition Disorders / Q000209:etiology* / Q000503:physiopathology; D017707:Erythrocyte Transfusion / Q000009:adverse effects* / Q000379:methods*; D006242:Haptoglobins / Q000032:analysis; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D007858:Learning; D008297:Male; D008568:Memory; D008840:Microfilament Proteins / Q000032:analysis; D011446:Prospective Studies; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: C100745:Aif1 protein, rat; D000893:Anti-Inflammatory Agents; D002135:Calcium-Binding Proteins; D006242:Haptoglobins; D053583:Interleukin-1beta; D015850:Interleukin-6; D008840:Microfilament Proteins