In the Russian Federation, ischemic cerebral infarction is recorded annually in more than
450,000 people. It is the second most common cause of death after coronary heart disease.
The 30-day mortality rate after an ischemic cerebral infarction is more than 25%, and
during the following year about half of the patients die, which is more than 200,000
people. The consequences of stroke belong to the first place among the causes of primary
disability. No more than 15% of those who have suffered a stroke return to work or fully
perform their previous household duties, and the rest, due to disability, need lifelong
medical and social rehabilitation. To date, all candidate neuroprotective drugs tested in
various clinical trials have demonstrated insufficient efficacy . Therefore, the
development of new approaches to the treatment of severe brain injuries of various
etiologies is one of the most important tasks of critical condition medicine.
Brain damage due to stroke triggers a number of pathophysiological reactions, which are
based on the accumulation of glutamate with the development of excitotoxicity. The effect
of glutamate on NMDA receptors is one of the main factors of neurodegenerative disorders.
Xenon is an anesthetic whose neuroprotective properties have been shown in many
experimental studies. However, the clinical part is still presented rather modestly.
After it was discovered that xenon is an inhibitor of NMDA receptors, it was shown that
xenon can protect neuronal cell cultures from damage caused by NMDA, glutamate, or
oxygen-glucose deprivation. It has been experimentally established that xenon is an
inhibitor of tissue plasminogen activator (tPA) and dose-dependent inhibits tPA-induced
thrombolysis; xenon inhalation after ischemia and reperfusion suppresses ischemic brain
damage and tPA-induced cerebral hemorrhages, and damage to the blood-brain barrier.
Exposure to xenon after transient ischemia in rats leads to a decrease in the volume of
infarction, depending on the concentration, exposure time and improvement of neurological
function 7 days after ischemia. To date, a role has been discovered in the implementation
of molecular mechanisms of xenon neuroprotection of double-pore potassium channels
(TREK-1), which provide a basic ion current that weakens neuronal excitability, thereby
protecting neurons from damage. The role of adenosine triphosphate (ATP)-sensitive
potassium channels of the plasmalemma in the realization of the protective properties of
xenon is also discussed in the scientific literature. It was shown that under in vitro
conditions in the culture of neurons, xenon protected them from damage caused by glucose
and oxygen deprivation by activating ATP-sensitive potassium channels in the plasmalemma.
There is evidence of the effect of xenon inhalation on the phosphorylation of glycogen
synthase-3ß, a key enzyme of the anti-apoptotic neuronal cascade, and an increase in the
pool of enzymes involved in the antioxidant protection of the brain. An experimental
study showed a distinct anti-inflammatory effect of this anesthetic, which consisted in
an increase in the ability of neutrophils to spontaneous apoptosis and a decrease in the
expression of adhesion molecules CD11b and CD66b on their surface after modeling an
inflammatory reaction. Also, the anti-inflammatory properties of xenon were shown when
modeling traumatic brain injury in vivo, when its exposure for 60 minutes caused a
significant decrease in the expression of pro-inflammatory genes NF-kB1 and NF-kB2,
responsible for the synthesis of cytokines and other molecules involved in inflammation.
Considering that the inflammatory reaction that forms in the first hours of ischemic
brain damage largely determines the severity of its further course, such an effect on
neutrophils can reduce the severity of damage to nervous tissue.
The most interesting is a randomized controlled trial performed by R. Laitio et al.
(2016), in which the use of xenon in combination with hypothermia in clinical practice
was studied for the first time. In patients who have undergone community-acquired cardiac
arrest, xenon inhalation at a concentration of 40 vol.% within 24 hours in combination
with hypothermia, led to less damage to the white matter of the brain than with patients
using hypothermia alone. The 6-month mortality rate was 27% in the xenon and hypothermia
group and 35% in the hypothermia group. However, the study was not powerful enough.
It is important to note that today, despite a large pool of convincing preclinical
studies proving the neuroprotective properties of xenon, there is not a single clinical
study of its use in ischemic stroke.
Therefore, the research objectives is to determine whether the strategy of using
xenon-oxygen mixture inhalation is better than oxygen-air mixture inhalation with respect
to the change in scores on the NIHSS, Rankin and Glasgow coma scales on day 7, the
duration of stay in the ICU and the frequency of nosocomial pneumonia.
