Microglial Modulation as a Therapeutic Avenue for Perioperative Neurocognitive Disorders: Unveiling Pathophysiological Mechanisms and Clinical Implications

Xuesheng Liu; Aobo Zhang

doi:10.1111/cns.70481

journal article Open Access Jul 01, 2025

Microglial Modulation as a Therapeutic Avenue for Perioperative Neurocognitive Disorders: Unveiling Pathophysiological Mechanisms and Clinical Implications

Xuesheng Liu

Aobo Zhang

CNS Neuroscience & Therapeutics Vol. 31 No. 7 · Wiley

View at Publisher Save 10.1111/cns.70481

Abstract

ABSTRACTBackgroundPerioperative neurocognitive disorders (PND) encompass a spectrum of cognitive impairments that arise from the preoperative phase and can persist for months after surgery, with a prevalence of up to 50% in elderly patients. These disorders, including postoperative delirium and sustained cognitive decline, significantly reduce patient quality of life and impose substantial burdens on healthcare systems. Despite extensive research, the underlying pathophysiological mechanisms remain inadequately understood, limiting the development of effective treatments. Increasing evidence highlights neuroinflammation as a central factor in PND, with microglia—the resident immune cells of the central nervous system—playing a key role in mediating inflammatory responses that lead to cognitive dysfunction.MethodsThis review comprehensively analyzes the role of microglia in the pathogenesis of PND. It details key perioperative triggers of microglial activation, such as surgical stress, anesthesia, and systemic inflammation. The review further examines preclinical interventions aimed at modulating microglial function, including depletion strategies, polarization toward anti‐inflammatory phenotypes, and inhibition of inflammatory pathways like NF‐κB and NLRP3.ResultsPreclinical studies demonstrate that dysregulated microglial activation results in excessive production of pro‐inflammatory cytokines, oxidative stress, and synaptic disruptions, which collectively contribute to neuronal injury and cognitive impairment. Interventions targeting microglial activation have shown efficacy in reducing neuroinflammation and preserving cognitive function in animal models.ConclusionsTargeting microglial activation represents a promising strategy for alleviating PND. However, challenges remain in clinical translation, necessitating advanced drug delivery platforms, personalized therapeutic approaches, and rigorous clinical validation. Advances in microglial modulation hold potential for improving postoperative cognitive outcomes and enhancing patient recovery.

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Details

Published: Jul 01, 2025
Vol/Issue: 31(7)
License: View

Authors

X

Xuesheng Liu

Department of Anesthesiology The Affiliated People's Hospital of Ningbo University Ningbo China

A

Aobo Zhang

Department of Neurosurgery The Second Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou China

Funding

National Natural Science Foundation of China Award: 82401598

Cite This Article

Xuesheng Liu, Aobo Zhang (2025). Microglial Modulation as a Therapeutic Avenue for Perioperative Neurocognitive Disorders: Unveiling Pathophysiological Mechanisms and Clinical Implications. CNS Neuroscience & Therapeutics, 31(7). https://doi.org/10.1111/cns.70481

Microglial Modulation as a Therapeutic Avenue for Perioperative Neurocognitive Disorders: Unveiling Pathophysiological Mechanisms and Clinical Implications

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