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Review
. 2022 Mar 28:16:843069.
doi: 10.3389/fncel.2022.843069. eCollection 2022.

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

Zhichao Li  1 , Youzhuang Zhu  2 , Yihan Kang  1 , Shangyuan Qin  1 , Jun Chai  1
Affiliations
Review

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

Zhichao Li et al. Front Cell Neurosci. .

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.

Keywords: general anesthesia; neuroinflammation; peripheral inflammation; postoperative cognitive dysfunction; preventive strategies; surgical trauma.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Surgical trauma stimulates the peripheral inflammatory response and immune activation. Injury-related pattern molecules dominated by HMGB1 recruit and activate peripheral immune cells and also promote the synthesis and release of a variety of inflammatory factors. Many inflammatory factors can be positively fed back to the secretion pathway for HMGB1 to induce and maintain the peripheral inflammatory response. Peripheral inflammation can spread to the central nervous system through several pathways [(1) Periventricular area; (2) Specific transporter; (3) TNF-α; (4) Homoreceptor; (5) Vagal nerve; and (6) Gut-brain axis], leading to central neuroinflammation and ultimately cognitive dysfunction. The two-way communication between the gut microbiome and the brain, termed the “gut-brain axis,” is involved in brain function and cognitive regulation.
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