# Unveiling the hidden dangers: a review of non-apoptotic programmed cell death in anesthetic-induced developmental neurotoxicity

## TL;DR

This review explores how non-apoptotic cell death types contribute to brain damage from anesthesia in developing brains.

## Contribution

It systematically analyzes non-apoptotic programmed cell death mechanisms in anesthetic-induced developmental neurotoxicity.

## Key findings

- Non-apoptotic PCDs like necroptosis and pyroptosis are key in AIDN.
- These pathways involve inflammation and oxidative stress.
- They offer new targets for preventing AIDN.

## Abstract

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.