Is xenon a Future Neuroprotectant?

Abstract

ReviewXenon, a noble gas discovered more than a century ago, has been known to exhibit anesthetic properties since 1946. Its effects are comparable to the commonly used anesthetic gas, nitrous oxide, and have been well defined (Table 1). Recently, its notable safety and efficacy as an inhalational anesthetic have been studied in various clinical settings [1,2]. However, high manufacturing costs owing to its rarity in the atmosphere remain the limiting factor in its widespread clinical application.As an antagonist of the NMDA subtype of the glutamate receptor [3], xenon has been extensively investigated for its molecular action in neuroprotection against acute neuronal injury. In this review, we aim to briefly describe the NMDA receptor-related mechanisms of ischemic brain injury and focus chiefly on the research progress into xenon's neuroprotective effects and paradigms. NMDA receptor & glutamate excitotoxicityGlutamate is a predominant excitatory neurotransmitter in the mammalian CNS [4]. When intensely activated, it can be toxic to neurons in a range of acute CNS injury conditions [5], including stroke [6], hypoglycemia [7], trauma [8] and status epilepticus [9]. Excess glutamate is also implicated in neurodegenerative conditions [10] with involvement of the NMDA subtype [11,12].Neuronal function and survival relies on a constant supply of oxygen and glucose to produce ATP through glycolysis and mitochondrial respiration. In ischemia and hypoglycemia, energy deficiency results in the dysfunction of the presynaptic neurotransmitter release and leads to a net increase in extracellular glutamate, causing neurotoxicity [13]. Excess glutamate activates its postsynaptic receptors, namely NMDA, a-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and kainate (KA). The activation of AMPA receptors depolarizes the cell and simultaneously unblocks the NMDA channels (by the removal of the Mg 2+ block), thus permitting Ca 2+ entry. Depolarization opens voltageactivated calcium channels, allowing an influx of Ca 2+ ions, as well as H 2 O molecules, down the osmotic gradient into the cell [14][15][16], subjecting the cells to cytotoxicity.The endoplasmic reticulum and mitochondria act as vast storage and regulators for Ca 2+ ions. Beyond a critical point, calcium overload disrupts mitochondrial function. It promotes intracellular enzyme activation systems including lipases, proteases and endonucleases, which cause an overwhelming production of free oxygen radicals, synthesis of nitric oxide [17], mitogen-activated protein kinase (MAPK) [18] and related toxic reaction products, leading to acute neuronal death [11,[19][20][21]. The inner mitochondrial membrane is also disrupted and causes the oxidation of the proteins involved in ATP production [22], reducing energy available for membrane pumps and resulting in apoptosis.Apoptosis is often associated with excitotoxicity, although the link is not well established. A multistep mechanism regulates apoptosis [23], involving the presence of at least two distinct checkpoints -on...

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“…Monoatomic noble gases are constituted by Helium (He), Neon (Ne), Argon (Ar), Krypton (Kr), Xenon (Xe) and Radon (Rd) and act as oxygen depletants. Xenon also shows aesthetical properties through an antagonism of glycine-site N-methyl-D-aspartate (NMDA) receptor [5] and was recently added on the list of substances banned by the World Anti-doping Agency (WADA) because of its performance-enhancing properties [6]. Radon is also classified as noble gas but shows radioactivity and carcinogenicity properties [7].…”

The Place of Gas Analysis in Forensic Toxicology

“…Xenon also shows aesthetical properties through an antagonism of glycine-site N-methyl-D-aspartate (NMDA) receptor [5] and was recently added on the list of substances banned by the World Anti-doping Agency (WADA) because of its performance-enhancing properties [6]. Radon is also classified as noble gas but shows radioactivity and carcinogenicity properties [7].…”