SSU researchers were the first in the world to stimulate cerebral lymphatic vessels in brain tissues during sleep. New non-invasive technologies offer great opportunities to cleanse the brain of toxins
On the Day of Russian Science, this material opens a cycle about laboratories, research, development and projects of regional universities from the Priority 2030 list.
Night studies
The brain behavior during sleep is studied by the Smart Sleep laboratory of the Saratov National Research State University named after N.G. Chernyshevsky. Her work is focused on research in the field of neuroregenerative medicine and the creation of “smart devices”. Members of the scientific group are studying the rehabilitation possibilities of special lymphatic vessels of the brain.
Developing and, in fact, rediscovering the ideas of two hundred years ago by the Italian anatomist Paolo Mascagni about the lymphatic system of the meninges of the brain, modern researchers are learning to use the possibilities of “invisible vessels”. Seven years ago, American scientists successfully repeated the Italian experiment. It became clear that the brain is able to turn on immune defenses and regulate the removal of toxins and metabolites, that is, metabolic products of brain tissues. Saratov scientists asked themselves the question: how does this happen and how to influence it? The result of the painstaking and operational work of researchers was pioneering results on the discovery of transparent lymphatic vacuum cleaners in the human brain, which remove toxins from its tissues.
This discovery was the impetus for the expansion of scientific ideas about the restorative functions of the brain. The team of the Smart Sleep laboratory managed to attract foreign colleagues to the joint work, for example, Thomas Penzel, a leading researcher in the physiology of sleep, head of the interdisciplinary somnology center at the Charité clinic (Berlin), and academician Jurgen Kurtz (Humboldt University in Berlin), who founded a new direction on the study of sleep as a marker of the state of the blood-brain barrier responsible for maintaining brain health.
Oksana Semyachkina-Glushkovskaya, Head of the Department of Human and Animal Physiology, Faculty of Biology, SSU, Deputy Head for Commercialization of Scientific Developments of the Scientific Medical Center:
“Now there are 50 people in the team, half of them are young scientists. Since they are studying sleep, the research takes place both at night and during the day. The laboratory unfolded on 165 sq. m. There are special rooms for working with cell cultures, a vivarium with animals without pathogenic microbes, a surgical unit. Before entering these rooms, specialists must put on special suits every time. The work is carried out on a microscope with the function of multiphoton microscopy. In this configuration, it is the only one in our country. The device performs deep scanning of living objects in real time, allowing you to safely and harmlessly work with different organisms.”
From postpartum trauma to Alzheimer’s
Scientists themselves compare the night work of transparent cerebral lymphatic vessels with a vacuum cleaner. During sleep, the brain actively works to restore its functions and “get rid” of toxic molecules accumulated during the day. Figuratively speaking, he “takes a shower” to cleanse himself of metabolites. At this moment, invisible vessels are activated. They help to remove toxins of various origins from the brain, including those accumulated in the blood after an intracranial hemorrhage.
Understanding and controlling these processes can be widely applied in practice and become a successful example of personalized medicine. For example, in Alzheimer’s disease, such non-invasive technologies can be used to remove a toxic protein. In other cases, stimulation can help to remove blood from the brain, since in an aneurysm or stroke, it begins to flow out precisely through the lymphatic vessels.
Another example, which is now in the focus of attention of the Saratov team, is the restoration of the brain of newborns from postpartum microtraumas. In this case, the fact plays into the hands of scientists that in the first month of a baby’s life, cerebral lymphatic vessels are especially active: other mechanisms for removing fluid from the brain are not yet operating. Brain damage of various sizes that occurs during childbirth causes hematomas in babies. In the future, this can negatively affect various brain functions: from speech and logic to concentration. The ability to naturally “pump out” the accumulated blood significantly increases the chances for a positive development of the newborn.
Born in a hat
The practical application of new technologies is associated with the development of portable gadgets: caps or headphones that stimulate the work of transparent lymphatic vessels in newborns during sleep. They can be used not only in maternity hospitals and clinics, but also at home.
In such devices, light and inaudible sound act as stimuli. EEG electrodes on the cap record the stages of sleep. The program, developed by the scientists of the “Smart Sleep” laboratory and sewn into the device, determines the phase of deep sleep: the time when the lymphatic system of the brain is activated. At this moment, the light guides in the cap automatically give stimulating signals to the cerebral lymphatic vessels. The process of cleaning tissues from metabolites and harmful substances is launched.
Preclinical trials on mice are being carried out at the Saratov laboratory of the Saratov State University, clinical trials will begin in the coming months at the Volga Research Medical University. Partners from the Charité clinic will deal with the automated delivery of exposure. The project at the intersection of medicine, physics and biology shows the real possibilities of an interdisciplinary approach of modern universities and their partners.
Lymphatic drug delivery
In addition to studying invisible vessels, the Smart Sleep laboratory team is developing the Lymph Window project to deliver drugs to the brain to fight tumors.
Oksana Semyachkina-Glushkovskaya:
“We injected drugs into the cervical lymph nodes. It turned out that there is a retrograde current that flows not only down, but also up. When I worked in Korea, I was shown special points on the neck, which are supplied by lymph vessels. If microdoses of the drug are injected into these points, they accumulate, including in the tumor itself.
The uniqueness of our developments is that they are non-invasive and can be used in a hospital for the treatment, in particular, of brain tumors. We are the only ones who represent these developments in the international arena, so they are of great interest from well-known scientific foundations in our country, China and America. We received the first patent in our country for non-invasive drug delivery to the brain.”
The projects of the “Smart Sleep” laboratory served as the basis for one of the strategic projects of the SSU Development Program, won by the university within the “Priority 2030”. So in the coming years, Saratov researchers have something to do. Priority areas of work in 2022: “Drug delivery to the brain and treatment of glioma with loud music”, “New era in tissue transplantation: test-tube gabion scaffolds for the treatment of spinal cord injuries”, “Lymph window to the brain: new methods of delivery medicines”, “Night therapy for Alzheimer’s disease”, “Pioneer non-invasive phototechnology for the treatment of glioma”.