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.

Difficulties in Understanding Postoperative Cognitive Dysfunction

“…However, it's frustrating to say that after all these years of research, maybe the only risk factor of POCD we have known for sure is the increasing age (13). Tim Johnson et al (14) reported that the incidences of POCD among middleaged (40-60 years old) patients at 7 days and three months after surgery were 19.5% and 6.2% , respectively, a little lower than those of the elderly patients.…”

“…Jiang et al (30) found that oxidative stress can lead to neural injuries and was widely studied in various neurodegenerative diseases. Compared with non-POCD rats, the malondialdehyde (MDA) level was significantly higher and the activity of superoxide dismutase (SOD) was significantly lower in rats developing POCD (13), which were both the markers of oxidative status. Using proteomic analysis, Li et al (31) reported that the expression levels of four oxidative stress related proteins including SOD1, glutathione S-transferase P (GSTP1), peroxiredoxin 2 (PRDX2) and aldose reductase (ADR), were significantly changed in POCD rats.…”

Dementia With Lew Body

“…81 The diagnosis of POCD is difficult because there is no recognized diagnostic criteria of POCD. However, it is usually diagnosed based on the performance of neuropsychological testing administered before and after the surgery.…”

“…[83][84][85] Possible causes of POCD are the type and duration of anesthesia/surgery, inflammation, hypoxemia, hypotension, neurodegeneration, and patient vulnerability 82 including old age, severity of coexisting illness, postoperative infections, respiratory complications, and a second operation. 86,87 The POCD is the most frequently reported following cardiac surgery and is also known to occur in other surgical procedures 81 The molecular mechanism underlying POCD is not clearly understood yet. Research has shown that the POCD is primarily associated with synaptic dysfunction and loss.…”

Protective effects of parecoxib on rat primary astrocytes from oxidative stress induced by hydrogen peroxide

“…Supporting the involvement of oxidative stress in POCD, Li et al (2015) performed protein expression profiling analysis of the hippocampus to explore the different proteins between normal control aged rats and aged rats with POCD, and found that oxidative stressrelated pathways were dysregulated in POCD. An et al (2013) also reported that oxidative stress, as well as increased iron accumulation, might be involved in the pathogenesis of POCD. However, the underlying molecular pathways associated with oxidative stress in POCD remain largely unknown.…”