Evaluating the efficacy of Xenon gas as a neuroprotective treatment in traumatic brain injury: a narrative review

Abstract Traumatic brain injury (TBI) is a primary global health concern, leading to long-term cognitive, neurological, and functional impairments. Secondary injury mechanisms, including excitotoxicity, oxidative stress, apoptosis, and neuroinflammation, contribute substantially to poor outcomes. Neuroprotective interventions that target these mechanisms are urgently needed. Xenon gas has emerged as a promising candidate due to its unique neuroprotective properties, including modulation of the N-methyl-D-aspartate (NMDA) receptor, anti-apoptotic effects, and anti-inflammatory actions. This narrative review critically evaluates Xenon gas as a neuroprotective intervention in TBI. A narrative review was conducted using PubMed, Scopus, Web of Science, and Google Scholar to identify studies evaluating Xenon gas as a neuroprotective agent in TBI. Search terms included “Xenon,” “neuroprotection,” and “traumatic brain injury,” including both in vivo and in vitro studies. Articles published in English without date restrictions were considered. Data were synthesized qualitatively, emphasizing experimental outcomes, mechanisms, and innovative delivery approaches. Preclinical studies consistently demonstrate that Xenon gas reduces neuronal injury, mitigates neuroinflammation, preserves cognitive and motor function, and improves survival in animal and in vitro models of TBI. Innovative delivery strategies, such as microbubbles and ultrasound-mediated delivery, allow for targeted cerebral administration and enhance therapeutic efficacy. Across studies, Xenon was generally well-tolerated, with minimal adverse effects reported. No clinical trials in human TBI patients were identified, highlighting a significant translational gap. Xenon gas exhibits multifaceted neuroprotective effects in preclinical TBI models, suggesting significant therapeutic potential. Its mechanisms of action, safety profile, and innovative delivery strategies support further investigation. However, rigorous clinical trials are needed to evaluate efficacy, optimize dosing and administration, and determine real-world applicability in human TBI patients. Addressing these gaps is crucial for translating Xenon therapy from the bench to the bedside.