EEG biomarkers of activation of the lymphatic drainage system of the brain during sleep and opening of the blood-brain barrier.

The lymphatic drainage system of the brain (LDSB) is the removal of metabolites and wastes from its tissues. A dysfunction of LDSB is an important sign of aging, brain oncology, the Alzheimer's and Parkinson's diseases. The development of new strategies for diagnosis of LDSB injuries can improve prevention of age-related cerebral amyloid angiopathy, neurodegenerative and cerebrovascular diseases. There are two conditions, such as deep sleep and opening of the blood-brain-barrier (OBBB) associated with the LDSB activation. A promising candidate for measurement of LDSB could be electroencephalography (EEG). In this pilot study on rats, we tested the hypothesis, whether deep sleep and OBBB can be an informative platform for an effective extracting of information about the LDSB functions. Using the nonlinear analysis of EEG dynamics and machine learning technology, we discovered that the LDSB activation during OBBB and sleep is associated with similar changes in the EEG θ-activity. The OBBB causes the higher LDSB activation vs. sleep that is accompanied by specific changes in the low frequency EEG activity extracted by the power spectra analysis of the EEG dynamics combined with the coherence function. Thus, our findings demonstrate a link between neural activity associated with the LDSB activation during sleep and OBBB that is an important informative platform for extraction of the EEG-biomarkers of the LDSB activity. These results open new perspectives for the development of technology for the LDSB diagnostics that would open a novel era in the prognosis of brain diseases caused by the LDSB disorders, including OBBB.

Transcranial Photobiomodulation of Clearance of Beta-Amyloid from the Mouse Brain: Effects on the Meningeal Lymphatic Drainage and Blood Oxygen Saturation of the Brain.

Here, we demonstrate the therapeutic effects of transcranial photobiomodulation (tPBM, 1267 nm, 32 J/cm2, a 9-day course) in mice with the injected model of Alzheimer's disease (AD) associated with accumulation of beta-amyloid (Aß) in the brain resulting in neurocognitive deficit vs. the control group (CG) (the neurological severity score (NNS), AD 3.67 ± 0.58 vs. CG 1.00 ± 0.26%, p < 0.05) and mild cerebral hypoxia (AD 72 ± 6% vs. CG 97 ± 2%, p < 0.001). The course of tPBM improved neurocognitive status of mice with AD (NNS, AD 2.03 ± 0.14 vs. CG 1.00 ± 0.26, vs. 2.03 ± 0.14, p < 0.05) due to stimulation of clearance of Aß from the brain via the meningeal lymphatic vessels (the immunohistochemical and confocal data) and an increase in blood oxygen saturation of the brain tissues (the pulse oximetry data) till 85 ± 2%, p < 0.05. These results open breakthrough strategies for non-pharmacological therapy of AD and clearly demonstrate that tPBM might be a promising therapeutic target for preventing or delaying AD based on stimulation of oxygenation of the brain tissues and activation of clearance of toxic molecules via the cerebral lymphatics.

Mechanisms of Sound-Induced Opening of the Blood-Brain Barrier.

The blood-brain barrier (BBB) poses a significant challenge for drug delivery to the brain. The limitations of our knowledge about the nature of BBB explain the slow progress in the therapy of brain diseases and absence of methods for drug delivery to the brain in clinical practice. Here, we show that the BBB opens for high-molecular-weight compounds after exposure to loud sound (100 dB 370 Hz) in rats. The role of stress induced by loud sound and the systemic and molecular mechanisms behind it are discussed in the framework of the BBB. This opens an informative platform for novel fundamental knowledge about the nature of BBB and for the development of a noninvasive brain drug delivery technology.

Phenomenon of music-induced opening of the blood-brain barrier in healthy mice.

Music plays a more important role in our life than just being an entertainment. For example, it can be used as an anti-anxiety therapy of human and animals. However, the unsafe listening of loud music triggers hearing loss in millions of young people and professional musicians (rock, jazz and symphony orchestra) owing to exposure to damaging sound levels using personal audio devices or at noisy entertainment venues including nightclubs, discotheques, bars and concerts. Therefore, it is important to understand how loud music affects us. In this pioneering study on healthy mice, we discover that loud rock music below the safety threshold causes opening of the blood-brain barrier (OBBB), which plays a vital role in protecting the brain from viruses, bacteria and toxins. We clearly demonstrate that listening to loud music during 2 h in an intermittent adaptive regime is accompanied by delayed (1 h after music exposure) and short-lasting to (during 1-4 h) OBBB to low and high molecular weight compounds without cochlear and brain impairments. We present the systemic and molecular mechanisms responsible for music-induced OBBB. Finally, a revision of our traditional knowledge about the BBB nature and the novel strategies in optimizing of sound-mediated methods for brain drug delivery are discussed.

Meningeal Lymphatic Pathway of Brain Clearing From the Blood After Haemorrhagic Injuries.

This seems to be the time to gain new knowledge about the meningeal lymphatic system and a deeper understanding of its anatomy and physiology. Although it is known that the meningeal lymphatics present in the layers of the brain, limited information is available about the role of this system in brain function. Here, for the first time we clearly demonstrate that the meningeal lymphatic pathway is involved in brain clearing from the blood after intracranial hemorrhage associated with hypoxia and forms a connective bridge between interstitial, cerebral spinal fluid and peripheral lymphatics. We also show that the development of methods to stimulate meningeal lymph flow after hemorrhagic evidence in the brain might be a neuroprotective strategy for effective recovery of the brain after a cerebrovascular catastrophe.