title: Surgical trauma induces iron accumulation and oxidative stress in a rodent model of postoperative cognitive dysfunction.
abstract: Postoperative cognitive dysfunction (POCD) is recognized as a complication after surgery in the elderly. The exact pathogenic mechanisms of POCD are still unknown. In this study, we investigated the role of iron accumulation within the central nervous system in the development of cognitive dysfunction in rats following splenectomy. Cognitive function was assessed using a Morris water maze on postoperative days 1, 3, and 7. Impaired cognitive function was observed on days 1 and 3 after splenectomy, while an anesthesia-alone group showed no significant difference from the control. Serum iron levels decreased and brain iron content increased on days 1 and 3 after surgery, which was in parallel with the impairment of cognitive function. Furthermore, the levels of proteins involved in the maintenance of brain iron homeostasis, including ferritin, transferrin receptor 1, and iron regulatory protein 2, were significantly different at postoperative days 1 and 3 in the hippocampus of splenectomized animals when compared with those of the control. The alterations in iron homeostasis were accompanied by intensified oxidative stress as measured by increases in the lipid peroxidation product, malondialdehyde, and a decrease in the levels of superoxide dismutase activity. Overall, these findings suggest that the impaired cognitive function was primarily due to surgical trauma rather than anesthesia. Increased iron accumulation and oxidative stress in the brain, especially in the hippocampus, may be involved in the pathogenesis of POCD.
authors.affiliation: Anesthesia and Operation Center, Chinese PLA General Hospital, Haidian District, Beijing, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: An
authors.forename: Yang
authors.initials: Y
authors.lastname: Yue
authors.forename: Wen-Zhi
authors.initials: WZ
authors.lastname: Guo
authors.forename: Yu-Liang
authors.initials: YL
authors.lastname: Miao
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Mi
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Zhi-Li
authors.initials: ZL
authors.lastname: Lei
authors.forename: Shu-Jun
authors.initials: SJ
authors.lastname: Han
authors.forename: Lan
authors.initials: L
authors.lastname: Dong
mesh_terms: D000818:Animals; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000473:pathology*; D004789:Enzyme Activation; D057075:Enzyme Assays; D005293:Ferritins / Q000097:blood; D006706:Homeostasis; D007501:Iron / Q000097:blood / Q000378:metabolism*; D035942:Iron Regulatory Protein 2 / Q000378:metabolism; D007858:Learning / Q000502:physiology; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D018782:Maze Learning; D018384:Oxidative Stress; D011183:Postoperative Complications / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011990:Receptors, Transferrin / Q000378:metabolism; D013156:Splenectomy / Q000009:adverse effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D011990:Receptors, Transferrin; C545564:Tfrc protein, rat; D008315:Malondialdehyde; D005293:Ferritins; D007501:Iron; D013482:Superoxide Dismutase; D035942:Iron Regulatory Protein 2