Technology of the photobiostimulation of the brain's drainage system during sleep for improvement of learning and memory in male mice.

In this study on healthy male mice using confocal imaging of dye spreading in the brain and its further accumulation in the peripheral lymphatics, we demonstrate stronger effects of photobiomodulation (PBM) on the brain's drainage system in sleeping vs. awake animals. Using the Pavlovian instrumental transfer probe and the 2-objects-location test, we found that the 10-day course of PBM during sleep vs. wakefulness promotes improved learning and spatial memory in mice. For the first time, we present the technology for PBM under electroencephalographic (EEG) control that incorporates modern state of the art facilities of optoelectronics and biopotential detection and that can be built of relatively cheap and commercially available components. These findings open a new niche in the development of smart technologies for phototherapy of brain diseases during sleep.

Low-Level Laser Treatment Induces the Blood-Brain Barrier Opening and the Brain Drainage System Activation: Delivery of Liposomes into Mouse Glioblastoma.

The progress in brain diseases treatment is limited by the blood-brain barrier (BBB), which prevents delivery of the vast majority of drugs from the blood into the brain. In this study, we discover unknown phenomenon of opening of the BBBB (BBBO) by low-level laser treatment (LLLT, 1268 nm) in the mouse cortex. LLLT-BBBO is accompanied by activation of the brain drainage system contributing effective delivery of liposomes into glioblastoma (GBM). The LLLT induces the generation of singlet oxygen without photosensitizers (PSs) in the blood endothelial cells and astrocytes, which can be a trigger mechanism of BBBO. LLLT-BBBO causes activation of the ABC-transport system with a temporal decrease in the expression of tight junction proteins. The BBB recovery is accompanied by activation of neuronal metabolic activity and stabilization of the BBB permeability. LLLT-BBBO can be used as a new opportunity of interstitial PS-free photodynamic therapy (PDT) for modulation of brain tumor immunity and improvement of immuno-therapy for GBM in infants in whom PDT with PSs, radio- and chemotherapy are strongly limited, as well as in adults with a high allergic reaction to PSs.

GB20 Pharmacopuncture As a Potential Method for Brain Drug Delivery via the Perivascular Spaces.

Background: The development of new methods of drug brain delivery is a crucial step for the effective therapy of the brain diseases. Pharma- and acupuncture are the forms of alternative therapy of the brain pathology, including an increase in the permeability of blood-brain barrier. However, the mechanisms of pharma- and acupuncture-mediated effects on the brain physiology remain not fully understood. Results: This pilot study on healthy mice clearly demonstrates the Evans Blue spreading in the mouse head and in the brain via the perivascular spaces (PVSs) of the trigeminal structure and the cribriform plate after the dye injection into the Feng Chi point (Galbladder 20, GB20). Conclusion: These results suggest that pharmacopuncture at GB20 can be a perspective method for brain drug delivery via PVSs.

Night Photostimulation of Clearance of Beta-Amyloid from Mouse Brain: New Strategies in Preventing Alzheimer's Disease.

The deposition of amyloid-ß (Aß) in the brain is a risk factor for Alzheimer's disease (AD). Therefore, new strategies for the stimulation of Aß clearance from the brain can be useful in preventing AD. Transcranial photostimulation (PS) is considered a promising method for AD therapy. In our previous studies, we clearly demonstrated the PS-mediated stimulation of lymphatic clearing functions, including Aß removal from the brain. There is increasing evidence that sleep plays an important role in Aß clearance. Here, we tested our hypothesis that PS at night can stimulate Aß clearance from the brain more effectively than PS during the day. Our results on healthy mice show that Aß clearance from the brain occurs faster at night than during wakefulness. The PS course at night improves memory and reduces Aß accumulation in the brain of AD mice more effectively than the PS course during the day. Our results suggest that night PS is a more promising candidate as an effective method in preventing AD than daytime PS. These data are an important informative platform for the development of new noninvasive and nonpharmacological technologies for AD therapy as well as for preventing Aß accumulation in the brain of people with disorder of Aß metabolism, sleep deficit, elderly age, and jet lag.

Brain Mechanisms of COVID-19-Sleep Disorders.

2020 and 2021 have been unprecedented years due to the rapid spread of the modified severe acute respiratory syndrome coronavirus around the world. The coronavirus disease 2019 (COVID-19) causes atypical infiltrated pneumonia with many neurological symptoms, and major sleep changes. The exposure of people to stress, such as social confinement and changes in daily routines, is accompanied by various sleep disturbances, known as 'coronasomnia' phenomenon. Sleep disorders induce neuroinflammation, which promotes the blood-brain barrier (BBB) disruption and entry of antigens and inflammatory factors into the brain. Here, we review findings and trends in sleep research in 2020-2021, demonstrating how COVID-19 and sleep disorders can induce BBB leakage via neuroinflammation, which might contribute to the 'coronasomnia' phenomenon. The new studies suggest that the control of sleep hygiene and quality should be incorporated into the rehabilitation of COVID-19 patients. We also discuss perspective strategies for the prevention of COVID-19-related BBB disorders. We demonstrate that sleep might be a novel biomarker of BBB leakage, and the analysis of sleep EEG patterns can be a breakthrough non-invasive technology for diagnosis of the COVID-19-caused BBB disruption.