Immune-Mediated Metabolic Kynurenine Pathways Are Involved in the Postoperative Cognitive Dysfunction after Cardiopulmonary Bypass

Abstract

Postoperative cognitive dysfunction (POCD) after cardiopulmonary bypass is a serious complication that can lead to personality changes, memory loss, reduction in the ability to learn, and other central nervous system dysfunctions. In recent years, there have been improvements in measures to protect the brain during surgery, although the incidence of cognitive dysfunction after cardiac surgery remains high (33 to 83% short-term and 20 to 60% long-term cognitive dysfunction). Despite the large amount of basic and clinical research on the incidence of POCD, its exact pathogenesis and complexity are not clear. Many studies have shown that the kynurenine pathway (KP) and cognitive function in humans are closely related. Some reports also show that the imbalance of some metabolites of the KP such as kynurenic acid and quinolinic acid (QUIN), which act in dynamic equilibrium under physiologic conditions, have effects on the central nervous system and can significantly affect cognitive function. Further studies have shown that inflammatory mediators may act on key enzymes of the KP causing KP-induced disorders. Severe inflammatory reaction occurs in patients undergoing cardiopulmonary bypass, which triggers metabolic pathways that are closely related to changes in cognitive function. In this review, we summarize that inflammation-induced metabolic kynurenine (KYN) pathway disorders are likely to have an important role in incidence of POCD after CPB surgery.

Activated Α7nachr Improves Postoperative Cognitive Dysfunction and Intestinal Injury Induced by Cardiopulmonary Bypass in Rats: Inhibition of the Proinflammatory Response Through the Th17 Immune Response

“…2E and F). This is consistent with the clinical cognitive impairment seen 24 to 48 h after cardiac surgery in most patients undergoing CPB [17-19]. …”

“…At 24 h after CPB, S-100β and NSE secretion was noticeably increased and apoptotic protein expression markedly increased. This is consistent with the POCD induced by CPB in most patients 24-48 h after cardiac surgery [17-19]. …”

“…Despite the continuous improvement in different cardiac surgical techniques, the incidence of postoperative complications remains high. Such complications, which include POCD [19], acute lung injury [20], kidney injury [21], and intestinal injury [22], have become an important obstacle to the development of cardiac surgery. In this study, 6% hydroxyethyl starch was injected into Sprague-Dawley rats through the right venous drainage and right femoral artery fusion to establish a CPB model.…”

Microarray Expression Profiles of lncRNAs and mRNAs in Postoperative Cognitive Dysfunction

“…Histone deacetylase is translated from HDAC gene, which is regulated by lncRNAs that was identified as differentially transcripted RNA in our study, indicating that lncRNAs exert their functions through regulating histone deacetylase activity in POCD pathogenesis. Yi et al (2015) reported the close relatedness of inflammatory response with the changes in cognitive function in cardiopulmonary bypass patients ( Yi et al, 2015 ). In a similar manner, interleukin-12 and its receptor were demonstrated to influence cognitive function ( Johansson et al, 2017 ; Vonder Haar et al, 2017 ; Wu et al, 2017 ).…”

“…The other moderately enriched-pathways like Jak-STAT signaling pathway, MAPK signaling pathway, and metabolic pathways in our study were also recorded to be involved in occurrence and development of POCD in rats’ model ( Wei et al, 2017 ). Inflammatory reaction can trigger several metabolic pathways, which are closely related to the changes in cognitive function in patients undergoing cardiopulmonary bypass ( Yi et al, 2015 ). It has been confirmed the phosphoinositide 3-kinase (PI3K)/AKT/glycogen synthase kinase-3β (GSK-3β) pathway are induced due to isoflurane anesthesia induced-inflammation, stress, and apoptosis, thus resulting to cognitive impairment ( Zhang Y. et al, 2016 ).…”