Oxana Semyachkina‐Glushkovskaya

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.

Cerebral small vessel disease (CSVD) is a leading cause of cognitive decline in elderly people and development of Alzheimer’s disease (AD). Blood–brain barrier (BBB) leakage is a key pathophysiological mechanism of amyloidal CSVD. Sleep plays a crucial role in keeping health of the central nervous system and in resistance to CSVD. The deficit of sleep contributes to accumulation of metabolites and toxins such as beta-amyloid in the brain and can lead to BBB disruption. Currently, sleep is considered as an important informative platform for diagnosis and therapy of AD. However, there are no effective methods for extracting of diagnostic information from sleep characteristics. In this review, we show strong evidence that slow wave activity (SWA) (0–0.5 Hz) during deep sleep reflects glymphatic pathology, the BBB leakage and memory deficit in AD. We also discuss that diagnostic and therapeutic targeting of SWA in AD might lead to be a novel era in effective therapy of AD. Moreover, we demonstrate that SWA can be pioneering non-invasive and bed–side technology for express diagnosis of the BBB permeability. Finally, we review the novel data about the methods of detection and enhancement of SWA that can be biomarker and a promising therapy of amyloidal CSVD and CSVD associated with the BBB disorders.

A new application of the photodynamic treatment (PDT) is presented for the opening of blood-brain barrier (BBB) and the brain clearing activation that is associated with it, including the use of gold nanoparticles as emerging photosensitizer carriers in PDT. The obtained results clearly demonstrate 2 pathways for the brain clearing: (1) using PDT-opening of BBB and intravenous injection of FITC-dextran we showed a clearance of this tracer via the meningeal lymphatic system in the subdural space; (2) using optical coherence tomography and intraparenchymal injection of gold nanorods, we observed their clearance through the exit gate of cerebral spinal fluid from the brain into the deep cervical lymph node, where the gold nanorods were accumulated. These data contribute to a better understanding of the cerebrovascular effects of PDT and shed light on mechanisms, underlying brain clearing after PDT-related opening of BBB, including clearance from nanoparticles as drug carriers.

Intraventricular hemorrhage is one of the most fatal forms of brain injury that is a common complication of premature infants. However, the therapy of this type of hemorrhage is limited, and new strategies are needed to reduce hematoma expansion. Here we show that the meningeal lymphatics is a pathway to remove red blood cells from the brain's ventricular system of male human, adult and newborn rodents and is a target for non-invasive transcranial near infrared photobiomodulation. Our results uncover the clinical significance of phototherapy of intraventricular hemorrhage in 4-day old male rat pups that have the brain similar to a preterm human brain. The course of phototherapy in newborn rats provides fast recovery after intraventricular hemorrhage due to photo-improvements of lymphatic drainage and clearing functions. These findings shed light on the mechanisms of phototherapy of intraventricular hemorrhage that can be a clinically relevant technology for treatment of neonatal intracerebral bleedings.

The deposition of amyloid-β (Aβ) in the brain is a risk factor for Alzheimer's disease (AD). Therefore, new strategies for the stimulation of Aβ 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 Aβ removal from the brain. There is increasing evidence that sleep plays an important role in Aβ clearance. Here, we tested our hypothesis that PS at night can stimulate Aβ clearance from the brain more effectively than PS during the day. Our results on healthy mice show that Aβ clearance from the brain occurs faster at night than during wakefulness. The PS course at night improves memory and reduces Aβ 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 Aβ accumulation in the brain of people with disorder of Aβ metabolism, sleep deficit, elderly age, and jet lag.