What do transparent lymphatic vessels do in the brain? To answer this question, the world-class Smart Sleep Laboratory has been established at Saratov University.
The discovery of invisible vessels by American researchers was the first step. Who will do the next? Russia has this priority due to the prevailing ideal conditions that have united world-class scientists in the Smart Sleep Laboratory built in Saratov State University.
Mega-grant for smart technologies
The laboratory conducts the special research as a part of a mega-grant funded by the Ministry of Science and Higher Education of the Russian Federation. As Chair of the Department of Human and Animal Physiology, Deputy Head for the Commercialisation of Research Developments of the SSU Research Medical Centre Oksana Semyachkina-Glushkovskaya said, the strategy of megagrants is mainly aimed at developing smart technologies.
‘In our case these are portable neurorehabilitative smart technologies used to manage the restorative properties of sleep. It is no coincidence that our unit is called the Smart Sleep Laboratory. Today, researchers are finding new approaches to the development of brain function management systems. These opportunities have emerged not so long ago due to breakthrough discoveries in neurobiology.
Our American colleagues “re-discovered” these lymphatic vessels five years ago. And for the first time, an Italian anatomist Paolo Mascagni drew attention to them two centuries ago. He described them and created wax figures, which are still displayed in the Collection of Anatomical Pathology in Vienna. But such is the paradox of fate that no one could repeat that experiment after him. For about two centuries, there was a medical dogma about the absence of transparent lymphatic vessels in the brain which had purifying and protective functions in the body. And just today, when scientific concepts about the brain functions are changing, it has become possible to re-think Mascagni's discovery in terms of the development of fundamentally new technologies.
So in 2015 in the United States at the University of Virginia due to the progress in optical technology the investigators discovered invisible vessels for the first time, which were still “hiding” in the membranes of the brain and were invisible to researchers. It revolutionised science and made people reconsider their knowledge on how the brain functioned and on its regeneration. Scientists started talking about the fact that the brain had an immune system, it could actively defend itself against bacteria and viruses and also actively cleanse itself of toxins and metabolites. And if so then there are great prospects for the development of fundamentally new technologies we would not even dream of.
This upheaval event also captured the Saratov researchers, although it all started accidentally or rather as a random pattern. Oksana Semyachkina-Glushkovskaya went to a New York school on a completely different topic, where she listened to a lecture on the discovery of these vessels, and she became so inspired by the studies that after her return to Russia she re-wrote her project for Russian Science Foundation for three days and devoted it to a new topic about invisible vessels. After some time, she met a colleague from Hospital Charité, Thomas Penzel, who became the head of the mega-grant. Today, a unique team of performers includes world leaders in sleep research (Thomas Penzel, Interdisciplinary Center for Sleep Medicine at Hospital Charité, Berlin, Germany), meningeal lymphatic system (Jonathan Kipnis, the University of Virginia School of Medicine, Charlottesville, USA), and nonlinear methods for analysing complex biological signals (Jürgen Kurths, Humboldt University, Berlin, Germany). This is a young and strong team, the team where “one for all, and all for one”, they make discoveries using their intuition and at the borders of sciences, including medicine, physics, and biochemistry.’
Is it possible to control invisible vessels?
Today the team of Saratov scientists is studying invisible vessels during sleep. This unique phenomenon looks like this: when we fall asleep, the brain closes itself from the whole world in order to work for itself, to get rid of those products that have accumulated during the day, and the invisible lymphatic vessels function as vacuum cleaners. They are activated during sleep and cleanse brain tissues of toxic molecules accumulated during the day or during the development of diseases, for example, after intracranial haemorrhage.
Thus, the mega-grant combined the two discoveries into a new interdisciplinary research. SSU took the lead in this area and was the first in the world to start developing special technologies for studying invisible vessels in the brain, including unique portable smart technologies used to manage the restorative properties of sleep and aimed for neuroregeneration. These technologies detect characteristic slow waves of brain electrical activity during sleep, and these waves are associated with the activation of sleep cleansing properties and the stimulation of these processes due to the delivery of inaudible sound. Unique developments have shown the first results when the sleeping brain is effectively cleared of the toxic protein beta-amyloid or of blood after intracranial haemorrhages.
The search for lymphatic vessels in brain tissues and the study of their role was continued by the SSU scientists last year, now we are preparing several publications on this topic, and international experts are studying the results of the experiments.
The invisible vessels of the sleeping brain are a real breakthrough in medicine giving the prospects to cure such pathologies as Alzheimer disease, brain injuries, intracranial haemorrhages during sleep, without special drugs which in 90% of cases do not reach the brain due to the blood-brain barrier between blood and tissue.
Proven technologies will help stimulate the invisible lymphatic vessels to remove accumulated toxic protein. They can also be used to cleanse the brain of blood that is toxic to the brain. Indeed, with a stroke or aneurysm, blood from the brain tissue begins to flow to the periphery precisely through the lymphatic vessels, and in order to help a person, they must be stimulated. This is especially important for new-born babies. As it has turned out, in the first month of life, invisible vessels work most actively, while all other mechanisms for removing fluid from the brain do not work.
magic bonnet for new-born babies
This unique development of the Saratov scientists will allow new-born babies to effectively recover from brain microtraumas received during childbirth.
Even the most prosperous and natural childbirth sometimes turns out to be a difficult test for a small person striving to be born. When passing the birth canal, babies often experience superficial damage to the brain and sometimes even part of it. Such hematomas are very dangerous for the development of further functions – concentration of attention, speech, and logic. Therefore, it is necessary to diagnose such problem in time, to “pump out” the accumulated blood in a natural way – and only after that the positive development of the new-born is possible.
The current members of the research team, including neurologists and neonatologists of Saratov State Medical University, have carried out clinical trials of the new technologies. They are to be applied in neonatology this year. The portable equipment, which does not require special training and can be used even at home in the form of bonnets or headphones, will stimulate the brain vessels of babies during sleep.
As Oksana Semyachkina-Glushkovskaya said, two stimuli will be used: light and inaudible sound. The bonnet has EEG electrodes that record the stages of sleep. The programme developed by the scientists is embedded in it, and it allows them to detect the so-called sleeping therapeutic windows when the lymphatic system of the brain is activated. Through the light guides sewn into the bonnet a stimulating signal is sent into the lymphatic vessels which cleanse the brain tissue from toxins and metabolites.
For scientists 2021 will be a very busy year: they are going to get patents for new technologies, launch clinical trials, prepare articles for publication due to which they will be able to announce the results of the research at the international level. The article in the International Journal of Molecular Science presents the main ideas of the project, which will be implemented by the end of this year.
‘In Russia we are still the only ones who work in this field,’ stated Oksana Semyachkina-Glushkovskaya. ‘This is the first time such research is conducted and is of exceptional importance. It is associated with such important issues as a change in mentality and scientific concepts about brain functioning during sleep, the emergence of fundamentally new educational curricula as well as with the production of a creative impulse in the technological sector of the country, where highly competitive smart sleep gadgets are guaranteed to appear quickly on the world market, so that you will be able to manage brain regenerative properties even at home.
The mega-grant of the Government of the Russian Federation is a great honour for us, and we understand our responsibility for its results. This grant is a very important stimulating start for the development of research at Saratov University. We have spent more than half of its amount (85 million rubles) on the purchase of the only supermicroscope in our country with a special laser for the wide possibilities of multiphoton microscopy. It allows us to work with different organisms and harmlessly and thoroughly reveal the secrets of the living.’
Text by Tamara Korneva
Translated by Lyudmila Yefremova
Photos by Victoria Viktorova