Is Xenon a Future Neuroprotectant?

Table 1.  Physical and anesthetic properties of nitrous oxide and xenon.

	Nitrous oxide	Xenon
Molecular weight	44	131
Melting point (°C)	−90.8	−111.9
Boiling point (°C)	−88.5	−108.1
Blood/gas partition coefficient	0.47	0.115
MAC
• Human	1.04	0.71
• Dog	1.88	1.19
• Rat	2.22	1.61
• Mouse	1.54	0.95

MAC: Minimum alveolar concentration of inhalational anesthetics at steady state that prevents reaction to a standard surgical stimulus (skin incision) in 50 % of patients at 1 atmosphere.

Authors and Disclosures

Pamela Sun
Department of Anaesthetics, Pain Medicine & Intensive Care, Imperial College London, Chelsea and Westminster Hospital, London, UK Tel.: +44 208 746 8495 Fax: +44 208 237 5104 pamela.sun@imperial.ac.uk

Jianteng Gu
Department of Anaesthetics, Pain Medicine & Intensive Care, Imperial College London, Chelsea and Westminster Hospital, London, UK and, Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China Tel.: +44 208 746 8495 Fax: +44 208 237 5109 jianteng@hotmail.com

Mervyn Maze
Department of Anaesthetics, Pain Medicine & Intensive Care, Imperial College London, Chelsea & Westminster Hospital, London, UK Tel.: +44 208 746 8816 Fax: +44 208 237 5109 m.maze@imperial.ac.uk

Daqing Ma ^†
Department of Anaesthetics, Pain Medicine & Intensive Care, Imperial College London, London SW10 9NH, UK Tel.: +44 208 746 8495 Fax: +44 208 237 5109 d.ma@imperial.ac.uk

^†Author for correspondence
Department of Anaesthetics, Pain Medicine & Intensive Care, Imperial College London, London, SW10 9NH, UK Tel.: +44 208 746 8495 Fax: +44 208 237 5109 d.ma@imperial.ac.uk

Sidebar

Executive Summary

Background

• Acute neuronal injury has devastating consequences with increased risks of morbidity and mortality. Currently, there is a distinct lack of effective clinical strategies to obviate this problem.

• Xenon, a noble gas with anesthetic properties, exhibits neuroprotective effects. It is reliable, efficacious and nontoxic, and has been used safely in clinical settings in patients of all ages.

• Xenon blocks the NMDA subtype of the glutamate receptor, a pivotal step in the pathway towards neuronal death. The preclinical data obtained from animal models of stroke, neonatal asphyxia, global ischemia induced by cardiac arrest and traumatic brain injury reveal that xenon may be an ideal candidate as a neuroprotectant. It may also prevent anesthetic-induced neurodegeneration in the developing brain. Clinical translation may result in a new therapeutic avenue for patients suffering from acute neuronal injury.

• This review aims to briefly describe the NMDA receptor-related mechanisms of ischemic brain injury and focusing chiefly on the research progress of xenon's neuroprotective effects and paradigms.

Neuroprotection

• Stroke – subanesthetic concentration of xenon provided neuroprotection in in vivo rodent models of stroke.

• Perinatal hypoxia–ischemia injury – combination of xenon and hypothermia, synchronous or asynchronous, provided long-term neuroprotection in in vivo rodent neonates.

• Cardiac arrest – administration of xenon reduced neurohistopathological and apoptotic damage to preserve neurocognitive function, and compared favorably with total intravenous anesthesia during cerebral reperfusion after cardiac arrest in porcine models.

• Preventing neurotoxic effects induced by other anesthetics – xenon mitigated the neurotoxic effects caused by the commonly used anesthetics nitrous oxide and isoflurane in rodent neonates.

• Traumatic brain injury – postinjury administration of xenon significantly reduced secondary injury following initial trauma in an in vitro murine model.

Future perspective

• Development of technologies in refinement, economic delivery and recycling of xenon will be the next step forward in allowing large clinical trials to investigate the application of xenon as a neuroprotectant.