Mechanisms of Photostimulation of Brain's Waste Disposal System: The Role of Singlet Oxygen.

There is strong evidence that augmentation of the brain's waste disposal system via stimulation of the meningeal lymphatics might be a promising therapeutic target for preventing neurological diseases. In our previous studies, we demonstrated activation of the brain's waste disposal system using transcranial photostimulation (PS) with a laser 1267 nm, which stimulates the direct generation of singlet oxygen in the brain tissues. Here we investigate the mechanisms underlying this phenomenon.

Photostimulation of brain lymphatics in male newborn and adult rodents for therapy of intraventricular hemorrhage.

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.

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).

Brain Waste Removal System and Sleep: Photobiomodulation as an Innovative Strategy for Night Therapy of Brain Diseases.

Emerging evidence suggests that an important function of the sleeping brain is the removal of wastes and toxins from the central nervous system (CNS) due to the activation of the brain waste removal system (BWRS). The meningeal lymphatic vessels (MLVs) are an important part of the BWRS. A decrease in MLV function is associated with Alzheimer's and Parkinson's diseases, intracranial hemorrhages, brain tumors and trauma.

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.

Intranasal Delivery of Liposomes to Glioblastoma by Photostimulation of the Lymphatic System.

The blood-brain barrier (BBB) limits the delivery of majority of cancer drugs and thereby complicates brain tumor treatment. The nasal-brain-lymphatic system is discussed as a pathway for brain drug delivery overcoming the BBB. However, in most cases, this method is not sufficient to achieve a therapeutic effect due to brain drug delivery in a short distance.

Photodynamic Opening of the Blood-Brain Barrier and the Meningeal Lymphatic System: The New Niche in Immunotherapy for Brain Tumors.

Photodynamic therapy (PDT) is a promising add-on therapy to the current standard of care for patients with glioblastoma (GBM). The traditional explanation of the anti-cancer PDT effects involves the PDT-induced generation of a singlet oxygen in the GBM cells, which causes tumor cell death and microvasculature collapse. Recently, new vascular mechanisms of PDT associated with opening of the blood-brain barrier (OBBB) and the activation of functions of the meningeal lymphatic vessels have been discovered.

Photomodulation of Lymphatic Delivery of Bevacizumab to the Brain: The Role of Singlet Oxygen.

The blood-brain barrier (BBB) poses a significant challenge for drug delivery to the brain. Therefore, the development of safe methods for an effective delivery of medications to the brain can be a revolutionary step in overcoming this limitation. Using a quantum-dot-based 1267 nm laser (photosensitiser-free generation of singlet oxygen), we clearly show the photostimulation of lymphatic delivery of bevacizumab (BMZ) to the brain tissues and the meninges.

Music improves the therapeutic effects of bevacizumab in rats with glioblastoma: Modulation of drug distribution to the brain.

Background: The development of new methods for modulation of drug distribution across to the brain is a crucial step in the effective therapies for glioblastoma (GBM). In our previous work, we discovered the phenomenon of music-induced opening of the blood-brain barrier (OBBB) in healthy rodents. In this pilot study on rats, we clearly demonstrate that music-induced BBB opening improves the therapeutic effects of bevacizumab (BZM) in rats with GBM increasing BZM distribution to the brain along the cerebral vessels.

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.

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

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.

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.

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/cm, a 9-day course) in mice with the injected model of Alzheimer's disease (AD) associated with accumulation of beta-amyloid (Aβ) in the brain resulting in neurocognitive deficit vs. the control group (CG) (the neurological severity score (NNS), AD 3.67 ± 0.

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.

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.

Optical properties of brain tissues at the different stages of glioma development in rats: pilot study.

In this paper, measurements of the optical properties (diffuse reflectance, total and collimated transmittance) of brain tissues in healthy rats and rats with C6-glioma were performed in the spectral range from 350 to 1800 nm. Using these measurements, characteristic tissue optical parameters, such as absorption coefficient, scattering coefficient, reduced scattering coefficient, and scattering anisotropy factor were reconstructed. It was obtained that the 10-day development of glioma led to increase of absorption coefficient, which was associated with the water content elevation in the tumor.

Phenomenon of atypical vascular effects of epinephrine and an increase of photodynamic response by nitroglycerin in rats with colon adenocarcinoma: adrenergic and nitrergic mechanisms and novel applied aspects.

Using an original model of stress-induced colon adenocarcinoma, we uncover atypical vasorelaxation effects of a mucosa injection of epinephrine assessed by laser speckle contrast imaging and a significant increase of fluorescent intensity of 5-ALA/PpIX from malignant colon tissues by a mucosa injection of nitroglycerine. We clearly demonstrate a high activity of adrenergic and nitrergic mechanisms underlying this phenomenon and discuss their application in improving of optical approaches for effective diagnosis of gastrointestinal cancer.

Pilot study of transcranial photobiomodulation of lymphatic clearance of beta-amyloid from the mouse brain: breakthrough strategies for non-pharmacologic therapy of Alzheimer's disease.

In this pilot study, we analyzed effects of transcranial photobiomodulation (tPBM, 1267 nm, 32 J/cm) on clearance of beta-amyloid (Aβ) from the mouse brain. The immunohistochemical and confocal data clearly demonstrate the significant reduction of deposition of Aβ plaques in mice after tPBM vs. untreated animals.

Photodynamic opening of the blood-brain barrier and pathways of brain clearing.

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.

Photodynamic opening of blood-brain barrier.

Photodynamic treatment (PDT) causes a significant increase in the permeability of the blood-brain barrier (BBB) in healthy mice. Using different doses of laser radiation (635 nm, 10-40 J/cm) and photosensitizer (5-aminolevulinic acid - 5-ALA, 20 and 80 mg/kg, i.v.

Stress-Induced Stroke and Stomach Cancer: Sex Differences in Oxygen Saturation.

Sex differences in stress-related diseases such as stroke and stomach cancer are well established, but the mechanisms underlying this phenomenon remain unknown. Despite the fact that sexual hormones play an important role in the high resistance of females to harmful effects of stress compared with males, the regulation of oxygenation status can be a potential factor, which might explain sex differences in stress-induced cerebrovascular catastrophes in newborn rats and in mutagens activation in adult rats with stomach cancer.