Emerging Roles of Immune Cells in Postoperative Cognitive Dysfunction

Abstract

Postoperative cognitive dysfunction (POCD), a long-lasting cognitive decline after surgery, is currently a major clinical problem with no clear pathophysiological mechanism or effective therapy. Accumulating evidence suggests that neuroinflammation plays a critical role in POCD. After surgery, alarmins are leaked from the injury sites and proinflammatory cytokines are increased in the peripheral circulation. Neurons in the hippocampus, which is responsible for learning and memory, can be damaged by cytokines transmitted to the brain parenchyma. Microglia, bone marrow-derived macrophages, mast cells, and T cells in the central nervous system (CNS) can be activated to secrete more cytokines, further aggravating neuroinflammation after surgery. Conversely, blocking the inflammation network between these immune cells and related cytokines alleviates POCD in experimental animals. Thus, a deeper understanding of the roles of immune cells and the crosstalk between them in POCD may uncover promising therapeutic targets for POCD treatment and prevention. Here, we reviewed several major immune cells and discussed their functional roles in POCD.

Rosa caninaL. methanolic extract prevents heat stress‐induced memory dysfunction in rats

“…*** P < 0.001 versus control group. # P < 0.05, ## P < 0.01 and ### P < 0.001 versus normal saline (NS) group impairment and neuronal death (Castanon, Luheshi, & Layé, 2015;Fabrègue, Butkowski, Voigt, & de Jong, 2016;Liu & Yin, 2018). In the present study, treatment with RC reduced heat stress-induced protein expression of the pro-inflammatory cytokine TNF-in the hippocampus, which was associated with attenuation of HS-triggered cognitive deficits.…”

“…According to evidence, heat stress also affects systemic inflammatory responses, increasing levels of pro‐inflammatory cytokines, such as IL‐6 and TNF‐α, in the brain and blood (Chauhan et al., ; Lee et al., ; Moon et al., ; Starkie et al., ). Furthermore, excessive inflammation in the brain is linked to cognitive impairment and neuronal death (Castanon, Luheshi, & Layé, ; Fabrègue, Butkowski, Voigt, & de Jong, ; Liu & Yin, ). In the present study, treatment with RC reduced heat stress‐induced protein expression of the pro‐inflammatory cytokine TNF‐α in the hippocampus, which was associated with attenuation of HS‐triggered cognitive deficits.…”

Sevoflurane anesthesia impairs metabotropic glutamate receptor‐dependent long‐term depression and cognitive functions in senile mice

“…However, a wealth of literature has described the link between sevoflurane and postoperative complications, including POCD . A number of molecular mechanisms have been proposed to account for the cognitive decline induced by sevoflurane, among which the neuroinflammation induced by anesthesia combined with surgery is generally believed to serve as the trigger and is supported by several reports . For instance, Yang et al reported that anesthesia/surgery impaired the permeability of the blood–brain barrier, and caused an elevated production of interleukin‐6 in an age‐associated manner, accompanied by the prominent deficits in cognitive functions .…”

Observational study of long-term persistent elevation of neurodegeneration markers after cardiac surgery

“…Some emphasized the effect of hypotension/hypoxia, hypercarbia, and anesthetic toxicity as contributing factors. However, neuroinflammation occupies the most dominant place in a discussion of postoperative cognitive decline 3,11,18 . Post-cardiac surgery inflammation leads to an elevation in free radicals, acute phase proteins, complement abnormalities, and cellular abnormalities 3,18,19 .…”