Neuroinflammation as the Underlying Mechanism of Postoperative Cognitive Dysfunction and Therapeutic Strategies

Abstract

Postoperative cognitive dysfunction (POCD) is a common neurological complication following surgery and general anesthesia, especially in elderly patients. Severe cases delay patient discharge, affect the patient’s quality of life after surgery, and are heavy burdens to society. In addition, as the population ages, surgery is increasingly used for older patients and those with higher prevalences of complications. This trend presents a huge challenge to the current healthcare system. Although studies on POCD are ongoing, the underlying pathogenesis is still unclear due to conflicting results and lack of evidence. According to existing studies, the occurrence and development of POCD are related to multiple factors. Among them, the pathogenesis of neuroinflammation in POCD has become a focus of research in recent years, and many clinical and preclinical studies have confirmed the correlation between neuroinflammation and POCD. In this article, we reviewed how central nervous system inflammation occurred, and how it could lead to POCD with changes in peripheral circulation and the pathological pathways between peripheral circulation and the central nervous system (CNS). Furthermore, we proposed some potential therapeutic targets, diagnosis and treatment strategies at the cellular and molecular levels, and clinical applications. The goal of this article was to provide a better perspective for understanding the occurrence of POCD, its development, and preventive strategies to help manage these vulnerable geriatric patients.

Plasma microRNA-221-3p as a biomarker for POCD after non-cardiac surgery

“…Presently, there are several hypotheses about the pathogenesis of POCD, which are related to inflammation of the central nervous system, nerve cell apoptosis, dysfunction of the cholinergic nervous system, and oxidative stress injury. However, inflammation of the nervous system still plays an important role in the development of POCD [ 16 , 32 , 33 ]. According to our previous study, microRNA-221-3p could target IRF2 of astrocytes to increase IFN-α expression and regulate nervous system inflammation [ 9 ].…”

The Ferroptosis Inhibitor Liproxstatin-1 Ameliorates LPS-Induced Cognitive Impairment in Mice

“…Massive evidence showed that major surgeries could induce a widespread systemic inflammatory response, and multiple biomarkers of neuro-inflammatory response were widely observed to have an association to the pathophysiological changes underpinning POCD and cognitive deficits in clinical studies [ 4 , 5 ]. This conclusion was verified in multiple surgery rodent models in terms of its mechanism, showing that the upregulation of pro-inflammatory cytokines and inflammatory mediators in the central nervous system (CNS) could cause obvious cognitive impairment in animals, and that it could be blocked by anti-inflammatory agents [ 6 , 7 , 8 ]. Inflammation leads to oxidative stress, contributes to mitochondrial dysfunction [ 9 , 10 , 11 , 12 ], and induces a variety of metabolic disorders, such as iron metabolism disorders.…”

Molecular Mechanism of Xingnao Kaiqiao Pill for Perioperative Neurocognitive Disorder and Its Correlation With Immune and Inflammatory Signaling Pathways Based on Network Pharmacology and Molecular Docking

“…In this study, we used molecular docking stimulation to identify the binding ability between bioactive components of Xingnao Kaiqiao Pill and key targets encoded by hub genes. According to Figure 9 and According to the universally recognized pathogenesis, PND can be considered as a neuroinflammation disease (Subramaniyan and Terrando, 2019;Li et al, 2022). It has been found that there is a close connection between the nervous system and the immune system, and inhibiting the expression level of inflammatory factors or suppressing the immune response can reduce the symptoms of PND or the occurrence of PND (Mu et al, 2015).…”