2017, Semyachkina-Glushkovskaya, Oxana, Abdurashitov, Arkady, Dubrovsky, Alexander, Bragin, Denis, Bragina, Olga, Shushunova, Natalia, Maslyakova, Galina, Navolokin, Nikita, Bucharskaya, Alla, Tuchind, Valery, Kurths, Jürgen, Shirokov, Alexander

The meningeal lymphatic vessels were discovered 2 years ago as the drainage system involved in the mechanisms underlying the clearance of waste products from the brain. The blood–brain barrier (BBB) is a gatekeeper that strongly controls the movement of different molecules from the blood into the brain. We know the scenarios during the opening of the BBB, but there is extremely limited information on how the brain clears the substances that cross the BBB. Here, using the model of sound-induced opening of the BBB, we clearly show how the brain clears dextran after it crosses the BBB via the meningeal lymphatic vessels. We first demonstrate successful application of optical coherence tomography (OCT) for imaging of the lymphatic vessels in the meninges after opening of the BBB, which might be a new useful strategy for noninvasive analysis of lymphatic drainage in daily clinical practice. Also, we give information about the depth and size of the meningeal lymphatic vessels in mice. These new fundamental data with the applied focus on the OCT shed light on the mechanisms of brain clearance and the role of lymphatic drainage in these processes that could serve as an informative platform for a development of therapy and diagnostics of diseases associated with injuries of the BBB such as stroke, brain trauma, glioma, depression, or Alzheimer disease.

2016, Semyachkina-Glushkovskaya, Oxana, Borisova, Ekaterina, Abakumov, Maxim, Gorin, Dmitry, Avramov, Latchezar, Fedosov, Ivan, Namykin, Anton, Abdurashitov, Arkady, Serov, Alexander, Pavlov, Alexey, Zinchenko, Ekaterina, Lychagov, Vlad, Navolokin, Nikita, Shirokov, Alexander, Maslyakova, Galina, Zhu, Dan, Luo, Qingming, Chekhonin, Vladimir, Tuchin, Valery, Kurths, Jürgen

In this study, we analyzed the time-depended scenario of stress response cascade preceding and accompanying brain hemorrhages in newborn rats using an interdisciplinary approach based on: a morphological analysis of brain tissues, coherent-domain optical technologies for visualization of the cerebral blood flow, monitoring of the cerebral oxygenation and the deformability of red blood cells (RBCs). Using a model of stress-induced brain hemorrhages (sound stress, 120 dB, 370 Hz), we studied changes in neonatal brain 2, 4, 6, 8 h after stress (the pre-hemorrhage, latent period) and 24 h after stress (the post-hemorrhage period). We found that latent period of brain hemorrhages is accompanied by gradual pathological changes in systemic, metabolic, and cellular levels of stress. The incidence of brain hemorrhages is characterized by a progression of these changes and the irreversible cell death in the brain areas involved in higher mental functions. These processes are realized via a time-depended reduction of cerebral venous blood flow and oxygenation that was accompanied by an increase in RBCs deformability. The significant depletion of the molecular layer of the prefrontal cortex and the pyramidal neurons, which are crucial for associative learning and attention, is developed as a consequence of homeostasis imbalance. Thus, stress-induced processes preceding and accompanying brain hemorrhages in neonatal period contribute to serious injuries of the brain blood circulation, cerebral metabolic activity and structural elements of cognitive function. These results are an informative platform for further studies of mechanisms underlying stress-induced brain hemorrhages during the first days of life that will improve the future generation's health.