Neuroprotective and neurorestorative potential of xenon

Abstract

International audienceXenon is a monatomic gas that belongs to the family of noble gases. Like other noble gases, it is characterized by a filled valence shell and therefore exhibits low chemical reactivity. Paradoxically, xenon possesses a remarkable spectrum of biological effects that are of potential clinical interest. Xenon is an approved anesthetic drug with analgesic properties. In addition to that xenon is neuroprotective in preclinical models of focal and global brain ischemia, spinal cord ischemia and traumatic brain injury. These neuroprotective effects are generally observed at concentrations of xenon ranging from 35 to 75%. Although the activation of ATP-sensitive potassium channels or of two-pore potassium channels may explain some of the neuroprotective effects of xenon, the noble gas appears to work primarily by limiting the overstimulation of N-methyl-D-aspartate (NMDA) glutamate receptors under excitotoxic stress conditions. More specifically, xenon has been reported to compete with glycine, a co-agonist for NMDA receptor activation. Excitotoxic stress mediated through NMDA receptors is most generally associated to acute central nervous system insults such as ischemia and traumatic brain injury, but chronic, low-level overexcitation of these receptors is also a possible contributor to neuronal death in a number of chronic neurodegenerative conditions, including amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease (AD). The implication of excitotoxic stress in AD-mediated neurodegeneration is specifically supported by studies reporting the benefits of treatments with NMDA receptor antagonists in preclinical models of the disease. Of interest, one of these antagonists memantine has also a small beneficial effect on cognitive impairment in AD patients

The noble gas xenon provides protection and trophic stimulation to midbrain dopamine neurons

“…Interestingly, we found that xenon also worked as a trophic factor toward basal forebrain cholinergic neurons, a neuronal population at risk in this disorder (Lavaur et al . ,b).…”

Xenon Exerts Neuroprotective Effects on Kainic Acid-Induced Acute Generalized Seizures in Rats via Increased Autophagy

“…Previous studies have demonstrated the strong xenon neuroprotective effects (Metaxa et al, 2014 ; Lavaur et al, 2016a , b ; Zhang et al, 2019a , b ); however, the possible xenon neuroprotective effects and the underlying mechanisms in seizure-induced neuronal injury remain clear. In this study, we assessed the effects of xenon treatment on neuronal injury; moreover, we evaluated the role of autophagy in KA-induced acute generalized seizures and the involved xenon neuroprotective effects.…”

“…Excessive excitation of the N-methyl-D-aspartate receptor, which results from extracellular glutamate accumulation, causes acute nerve injury or even death, by activating calpain and the caspase-3 pathway in patients with epilepsy and in animal models of epilepsy (Baudry and Bi, 2016 ; Hoque et al, 2016 ; Ceccanti et al, 2018 ). Xenon treatment regulates the glutamate level by suppressing its uptake and efflux (Lavaur et al, 2016a ). This results in the upregulation of the anti-apoptotic protein Bcl-2 and downregulation of the pro-apoptosis protein Bax.…”

“…Xenon is clinically used as a safe anesthetic agent and is popular due to having almost no side effects. It has been recently receiving increased attention due to its superior neuroprotective effects, which have been confirmed in Alzheimer’s disease (Lavaur et al, 2016a , b ) and in ischemia/reperfusion injury (Cattano et al, 2011 ; Yang T. et al, 2012 ; Yang et al, 2014 ; Metaxa et al, 2014 ). Moreover, xenon treatment has been shown to exert similar neuroprotective effects and ameliorate cognitive impairment in intrauterine (Yang Y. W. et al, 2012 ) and neonatal asphyxia (Luo et al, 2008 ).…”

“…Xenon can attenuate over-excitation by the regulation of glutamate metabolism, through inhibiting glutamate uptake and efflux (Lavaur et al, 2016a , b ). Given the initiating role of over-excitation in neuronal injury and autophagy, as well as the effect of autophagy on the seizure-induced neuronal injury, we hypothesized that autophagy is closely related to the neuroprotective effects of xenon.…”