The main objective of the research is to study of permissible limits and conditions as well as effect of radon inhalation on convulsive seizures and development of epilepsy in experimental animal models (kindling, self-sustained status epilepticus, audiogenic seizures) and in a translational pilot study in adults with drugresistant (pharmacoresistand) epilepsy.
To achieve this goal the following tasks will be conducted:· To establish current chemical and radionuclide composition of Tskhaltubo mineral water, which has not been studied for the last 50 years;
· To study influence of different doses radon inhalation on development and manifestation of seizure activity in conditions of the already developed epileptogenic focus (in the kindling model);
· To study effect of different doses radon inhalation on the spontaneous seizures manifestation in the amygdala stimulation-induced self-sustained status epilepticus;
· To assess changes of the mechanisms of the various neurotransmitter systems (serotonin, noradrenalin and DOPA) in the limbic structures (hypoxemia, amygdala complex) as a result of radon inhalation before and after the development of convulsive reactions on rats models;
· To study influence of radon inhalation on the development and manifestation of the audiogenic seizures;
· To ascertain NO effect on neuronal activity and its influence on convulsive reactions after radon inhalation in the experimental rats’ hippocampus and amygdala by the changes of the levels of Glutamine Acid and GABA;
· To establish the 2nd phase of prospective clinical trial on effectiveness of radon inhalation with low doses during the 14 days as add-on therapy to the conventional anticonvulsive treatment in patients with pharmacoresistand focal epilepsy.
Radon is a radioactive inert gas which mainly produces a radiation that is widely used in cases of hypertension and brain disorders in aging. Among the well-known positive effect of radon therapeutic spas are the intensification of activity of such perfuse agents as increasing of adrenalin level in blood plasma.
Resort Tskaltubo, located in Georgia, has long been used for improving health in various disorders. Tskaltubo is rich with natural springs that are regarded as chloride-hydrocarbonate-sulfate-magnesium-calcium-sodium water. In the 70th of the 20th century important microelements such as iodine, bromine, magnesium, lithium, zinc, strontium and copper were detected in Tskaltubo mineral water. Analysis also showed that springs contain low concentration of radioactive radon (40 to 100 Bq/ M3) that could be considered as one of the cause of healing effect. Despite of the fact, that radon can damage human health in high concentration, even in those cases development of lung cancer were most strongly associated with cigarette smoking. Resort Tskhaltubo has long been used for improving health in various disorders. It is situated of 70 km from black sea, altitude 90-120 meter from sea level. Tskhaltubo is located in western Georgia and is regarded as chloride-hydrocarbonate-sulfate-magnesium-calcium-sodium water. It is characterized as stable and unchangeable by time. In the 70th of the 20th century important microelements such as iodine, bromine, magnesium, lithium, zinc, strontium and copper were detected in Tskhaltubo mineral water. Analysis also showed that springs contain low concentration of radioactive radon [40 to 100 Becquerel (Bq)] that could be considered as one of the cause of healing effect.
Numerous experimental studies have been provided in animal models to prove the positive effect of radioactive radon on various disorders. In recent previous experimental studies they were performed in rabbits to investigate the curative effects of radon hormesis (the effect of the substance through the impact on hormonal regulation) the changes of levels the lipid peroxide, the oxidative stress’s formative Nitrogen Oxide (NO) and the indicators of membrane conductivity of different organs were performed). The data of this studies indicate that the effect of radon hormesis (R-Ho) happens by the activation of NO and formation of hydrogen peroxide (H2O2) that activate of excessive NO production in microphages under the effect of interferon gamma and beta (INF-aa). As a result the increased production of NO activates peripheral microcirculation and central hemodynamic. In this reason NO can be considered as homeostatic modulator as well.
It is established that macrophage-killers are the important source of NO. By NO activation they suppress DNA synthesis of tumor cells and suppression of new tumor cells, anti-inflammatory, desensibility and sedative mechanisms. NO effects on activation of DOFA, DOFA-cines and DOFA-amino formation in blood; it is involved in regulation of the Na+, K+ and Ca++ ion changes, and play one of the main role in suppression of specific autoimmune and in activation of non-specific immune systems of the body.
One of the most important properties of radon is its analgesic, reparative-regenerative, immunomodulative, stress- inductive action. In our previous experimental studies radon inhalations within 7 days of 5-minute inhalations in aggressive rats decrease aggressiveness and they became non-aggressive, decrease the ratio of Glutamine Acid to GABA and increase the noradrenaline level. Hence, these studies proved that radon inhalations might cause physiological changes which impede the activity of some neurotransmitters in the brain.
Findings of previous studies clearly indicate possible benefit of therapeutic radon use on brain functioning. More profound and scientifically systematized approach is needed to determine uniqueness of Tskhaltubo water springs, investigation the mechanisms of radon effects on the excitatory and inhibitory functioning of CNS and further clinical studies to establish its effectiveness on humans..
R-Ho could have significant beneficial effect in patients with epilepsy that is one of the most common chronic neurological diseases. Epilepsy affects more than 50 million people in the world (1% of general population) and there are leaving more than 35 000 persons with active epilepsy in Georgia (8.8 per 1000). Epilepsy is more often revealed among children and in aging people. In 60-65% of cases seizures are fully controlled on adequate anticonvulsive drug treatment regimen and patients maintain higher psycho-social wellbeing. Among 1/3 of patients with epileptic seizures it is impossible to become seizure free despite adequate treatment and in such drug-resistant cases surgical treatment is considered. However, that method, unfortunately, is not justified in all cases and alternative methods such as ketogenic diet or vagus nerve stimulation are recommended.
Epilepsy is a bio-psycho-social condition as stigma, anxiety and depression are frequently associated with epilepsy that significantly decrease quality of life (QOL) of patients and their family members. Latest studies indicate on higher level of stigma, frequent occurrence of depression (30%) and decreasing the health-related QOL in patients with epilepsy mainly in cases with ongoing seizurs.
Pharmacoresistand seizures lead to considerable medico-social and economic problem. According to the International League Against Epilepsy (ILAE) the data unexpected deaths among people with epilepsy is estimated to be up to 27-fold higher in those with ongoing seizures compared to the ones who are seizure free. Patients with uncontrolled seizures have significant cognitive and social impairment that adversely affects their quality of life, as well as places substantial stress on their family members and care-givers. Thus, the number of patients with restricted psycho-social activities and limited opportunities for employment are increased due to disease. These patients require permanent social assistance and expensive medical treatment. According to all above-mentioned, pharmacoresistand epilepsy imposes considerable economic burden on health care system and society. In this light, elaboration of novel, effective treatment opportunity for those patients is a matter of prominent importance.
Highly qualified personnel - neurochemists, nuclear physicist, neurophysiologists, neurologists, system engineers, programmers and technicians with great experience in the field of biology, medical practice, analytical chemistry, nuclear physical methods of analysis, instrumentation, as well as programmers in the field of data processing and modeling will be engaged. The four Project participants are weapons experts.
