Xenon shows strongest evidence for neuroprotection against ischemic stroke and hypoxic-ischemic brain injuryNoble gases show promise in protecting brains after stroke

Noble gases were chemically inert elements that have attracted increasing interest because of their potential neuroprotective properties. Among them, xenon had long been used as an inhalational anesthetic, while xenon, argon, and helium had also been investigated for possible neuroprotective effects. This narrative review focused on acquired brain injury, particularly ischemic stroke, post-cardiac arrest hypoxic-ischemic brain injury, and traumatic brain injury. Preclinical studies had suggested that several noble gases might reduce secondary neuronal injury, although the strength and consistency of evidence varied across gases and experimental models. Proposed mechanisms included attenuation of excitotoxicity, apoptosis, oxidative stress, and neuroinflammation, although these pathways had not been fully clarified for all gases. This review summarizes and compares the available preclinical and early clinical evidence on xenon, argon, and helium in acquired brain injury. Among these gases, xenon currently had the strongest and most consistent evidence base, whereas evidence for argon remained heterogeneous and evidence for helium was limited. Although the preclinical findings were promising, clinical translation remains limited, and further standardized studies were needed to define efficacy, safety, timing of administration, and feasible delivery strategies.