Noble gas could protect stroke victims from brain damage

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Ezine

  • Published: Jan 12, 2017
  • Author: Ryan De Vooght-Johnson
  • Channels: Gas Chromatography
thumbnail image: Noble gas could protect stroke victims from brain damage

Surviving a stroke

During a stroke, a clot cuts off the blood supply to the brain, causing cells to be starved of nutrients and oxygen, and ultimately die. This happens to somebody approximately once every two seconds, and one in four of those cases the stroke will be fatal within a year.

During a stroke, a clot cuts off the blood supply to the brain, causing cells to be starved of nutrients and oxygen, and ultimately die. This happens to somebody approximately once every two seconds, and one in four of those cases the stroke will be fatal within a year. Those who survive may be left with irreversible brain damage that makes them dependent on others for their care.

Neuroprotective therapies aim to prevent these consequences, and have shown huge potential in early studies. One potential neuroprotective agent is xenon, a noble gas with well-characterised anaesthetic properties. By the same mechanism that xenon generates anaesthesia, it can also protect the brain by stopping cells from dying.

Xenon is a particularly promising neuroprotective drug because it can easily cross the blood–brain barrier and has very few side effects. However, there is a problem in delivering it to patients. On the operating table xenon is usually inhaled, but to achieve neuroprotective effects in this way requires unfeasibly high concentrations of the gas.

A new route to the brain

As xenon can’t deliver its neuroprotective effects by inhalation, there is a need for a new way to deliver the gas to the brain. In a paper recently published in Rapid Communications in Mass Spectrometry, researchers from the University of Texas Health Science Center describe such a way, using what they call ‘intrinsically echogenic liposomes’ or ELIPs. These balls of lipid are loaded with xenon gas, which can be released using ultrasound waves.

Although the researchers had already shown that these xenon-loaded particles prevent brain damage in rat models of stroke, they needed a way to measure the levels of xenon in blood to determine the precise amount needed for neuroprotection, and to control the quality of the liposomes.

The researchers used headspace analysis, whereby gas chromatography/mass spectrometry (GC-MS) is used to measure a gas in the space above a solution. They used this technique to measure concentrations of xenon in water, reconstituted Xe-ELIPs, and rat blood samples.

The xenon concentrations measured in the particles agreed well with those previously determined, confirming the accuracy of the method. The approach also provided flexibility as it could be used to measure a wide range of xenon levels in many different samples. It also has a low limit of detection (0.022% dissolved xenon, roughly 3 micromoles per millilitre of blood).

In rats, the authors showed that an injection of 6 milligrams of Xe-ELIP over just 6 minutes produced neuroprotective effects, including reduced brain cell death and improved function. Measurement of xenon in the rats’ bloodstream showed an average concentration of 14 micromoles—less than 15% of the previously estimated neuroprotective level.

Surprisingly potent

The study not only describes an innovative means of administering xenon but also a reproducible means of measuring the amount dissolved in a variety of fluids, including blood. “Our work enables quality control of xenon-loaded liposomes manufactured as a neuroprotective agent for the treatment of ischemic and haemorrhagic stroke,” summarises lead author Professor Melvin Klegerman.

The method can also accurately measure levels of xenon in blood, which is necessary to determine the concentrations needed for clinical effect. “Measurement of xenon in blood enables assessment of the pharmacokinetics of xenon release from the liposomes after injection,” adds Klegerman. And, promisingly, the findings suggest that xenon can have protective effects at concentrations much lower than previously thought. The technique could also be used for other biologically active noble gases, such as helium, which has been used to treat asthma and also has neuroprotective properties.

Related Links

Rapid Commun. Mass Spectrom., 2017, Early View paper. Klegerman et al. Gas chromatography/mass spectrometry measurement of xenon in gas-loaded liposomes for neuroprotective applications.

Critical Care, 2015, 19, 186. Stocchetti et al. Neuroprotection in acute brain injury: an up-to-date review.

Article by Ryan De Vooght-Johnson

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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