Perioperative neurocognitive disorders (PNDs) are common postoperative complications, particularly in elderly patients undergoing general anesthesia. While sevoflurane and isoflurane are widely used inhalational anesthetics, their association with PNDs requires deeper mechanistic investigation. Although apoptosis was traditionally considered the primary mechanism, recent evidence implicates non-apoptotic programmed cell death (PCD) pathways-necroptosis, ferroptosis, and pyroptosis-in PND pathogenesis. These pathways amplify neuroinflammation and neuronal damage through distinct molecular mechanisms. This review synthesizes current understanding of these PCD pathways in inhalational anesthetic-induced neurotoxicity, evaluating their molecular signatures and interactions. We identify critical knowledge gaps and propose research directions focusing on pathway dominance, crosstalk, and multi-target therapeutic strategies. These insights advance PND pathophysiology understanding and inform novel treatment development.

Anesthetic-induced developmental neurotoxicity (AIDN) can arise due to various factors, among which aberrant nerve cell death is a prominent risk factor. Animal studies have reported that repeated or prolonged anesthetic exposure can cause significant neuroapoptosis in the developing brain. Lately, non-apoptotic programmed cell deaths (PCDs), characterized by inflammation and oxidative stress, have gained increasing attention. Substantial evidence suggests that non-apoptotic PCDs are essential for neuronal cell death in AIDN compared to apoptosis. This article examines relevant publications in the PubMed database until April 2024. Only original articles in English that investigated the potential manifestations of non-apoptotic PCD in AIDN were analysed. Specifically, it investigates necroptosis, pyroptosis, ferroptosis, and parthanatos, elucidating the signaling mechanisms associated with each form. Furthermore, this study explores the potential relevance of these non-apoptotic PCDs pathways to the pathological mechanisms underlying AIDN, drawing upon their distinctive characteristics. Despite the considerable challenges involved in translating fundamental scientific knowledge into clinical therapeutic interventions, this comprehensive review offers a theoretical foundation for developing innovative preventive and treatment strategies targeting non-apoptotic PCDs in the context of AIDN.

Introduction: Age‐related neurodegenerative diseases (NDDs) and stroke represent significant public health challenges due to their high morbidity, mortality, and associated cognitive decline. Current therapeutic strategies often fall short in addressing the complex underlying pathological mechanisms, underscoring the urgent need for innovative treatment approaches. Ferroptosis, an iron‐dependent form of regulated cell death driven by lipid peroxidation, has emerged as a critical factor contributing to neuronal damage in NDDs and stroke. Methods: To explore how acupuncture‐related therapies may modulate ferroptosis and contribute to neuroprotection, we conducted a comprehensive narrative review. A systematic search was performed in PubMed using targeted keywords including “ferroptosis,” “interventions” (such as acupuncture, electroacupuncture, and moxibustion), and “diseases” (including age‐related neurodegenerative diseases and stroke). The search was restricted to articles published before April 2025 with full‐text availability in English. Results: This review consolidates recent findings on the potential of acupuncture‐related therapies to target ferroptosis in NDDs and stroke. Traditional acupuncture, electroacupuncture (EA), and moxibustion have shown promising neuroprotective effects through multiple mechanisms. Emerging evidence suggests that these interventions can regulate ferroptosis by modulating key molecular pathways involved in iron metabolism, lipid peroxidation, and oxidative stress. These actions are thought to alleviate synaptic dysfunction and slow cognitive decline—processes where ferroptosis plays a central role. Such insights enhance our understanding of how traditional Chinese medicine could influence cognitive outcomes in age‐related NDDs and stroke. Conclusion: Understanding the role of ferroptosis in NDDs and stroke is essential for developing novel therapeutics. Based on current findings, this review proposes future research directions aimed at integrating acupuncture into modern neurotherapeutic frameworks. Combining traditional medicine with contemporary medical approaches offers new opportunities for promoting brain health and improving patient outcomes.