Deferoxamine pre-treatment protects against postoperative cognitive dysfunction of aged rats by depressing microglial activation via ameliorating iron accumulation in hippocampus.
Postoperative cognitive dysfunction (POCD) is a common complication of elderly patients after surgery. The mechanisms of POCD have not been clarified. Iron accumulation is a feature of neurodegeneration. Recent reports showed that iron content was increased with impaired cognition induced by surgery. We sought to investigate whether iron chelation would attenuate POCD. In this study, male aged (18 months) Sprague-Dawley rats received 100 mg/kg deferoxamine or saline solution (0.9%) for 6 days before exploratory laparotomy. Cognition was evaluated by Morris water maze before and after surgery. Additional rats received deferoxamine or saline were used to determine hippocampal iron content, iron transport-related proteins (transferrin receptor, divalent metal transporter 1, ferroportin 1 and hepcidin), oxidative stress, microglial activation and brain cell apoptosis. It was found that deferoxamine improved postoperative spatial memory in aged rats. Deferoxamine significantly reduced hippocampal iron concentration and ferritin. Surgery increased divalent metal transporter 1 and hepcidin, decreased transferrin receptor and ferroportin 1, and enhanced ferroportin 1 mRNA. However, deferoxamine reversed the changes of these proteins. Furthermore, deferoxamine sharply reduced the hippocampal reactive oxygen species, malondialdehyde concentration and OX-42 that is a marker of microglia, which might reduce postoperative brain cell apoptosis. This study showed that deferoxamine may improve postoperative cognition of aged rats by ameliorating oxidative stress induced by hippocampal iron accumulation, microglial activation and brain cell apoptosis. This study suggests a potential therapeutic method for reducing POCD.
Department of Anesthesiology, Southwest Hospital, The Third Military Medical University, Chongqing, China; Department of Anesthesiology, No. 281 Hospital of People's Liberation Army, Hebei, China.
Ke
K
Pan
Department of Anesthesiology, Southwest Hospital, The Third Military Medical University, Chongqing, China.
Xiaojun
X
Li
Department of Anesthesiology, Southwest Hospital, The Third Military Medical University, Chongqing, China.
Yan
Y
Chen
Department of Anesthesiology, Southwest Hospital, The Third Military Medical University, Chongqing, China.
Dan
D
Zhu
Department of Anesthesiology, Southwest Hospital, The Third Military Medical University, Chongqing, China.
Yuping
Y
Li
Department of Anesthesiology, Southwest Hospital, The Third Military Medical University, Chongqing, China. Electronic address: 13908393339@vip.163.com.
Guocai
G
Tao
Department of Anesthesiology, University of Virginia, Charlottesville, VA, USA. Electronic address: zz3c@virginia.edu.
Zhiyi
Z
Zuo
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D027682:Cation Transport Proteins / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D003676:Deferoxamine / Q000008:administration & dosage*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects; D011183:Postoperative Complications / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011990:Receptors, Transferrin / Q000378:metabolism; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
D027682:Cation Transport Proteins; D003676:Deferoxamine; D007501:Iron; D018696:Neuroprotective Agents; D011990:Receptors, Transferrin; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
Aging; Deferoxamine; Hippocampus; Iron accumulation; Postoperative cognitive dysfunction