In this pilot study, we analyzed effects of transcranial photobiomodulation (tPBM, 1267 nm, 32 J/cm 2 ) 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. The behavior tests showed that tPBM improved the cognitive, memory and neurological status of mice with Alzheimer's disease (AD). Using of our original method based on optical coherence tomography (OCT) analysis of clearance of gold nanorods (GNRs) from the brain, we proposed possible mechanism underlying tPBM-stimulating effects on clearance of Aβ via the lymphatic system of the brain and the neck. These results open breakthrough strategies for a non-pharmacological therapy of Alzheimer's disease and clearly demonstrate that tPBM might be a promising therapeutic target for preventing or delaying Alzheimer's disease.
There is a hypothesis that augmentation of the drainage and clearing function of the meningeal lymphatic vessels (MLVs) might be a promising therapeutic target for preventing neurological diseases. Here we investigate mechanisms of photobiomodulation (PBM, 1267 nm) of lymphatic drainage and clearance. Our results obtained at optical coherence tomography (OCT) give strong evidence that low PBM doses (5 and 10 J/cm 2 ) stimulate drainage function of the lymphatic vessels via vasodilation (OCT data on the mesenteric lymphatics) and stimulation of lymphatic clearance (OCT data on clearance of gold nanorods from the brain) that was supported by confocal imaging of clearance of FITC-dextran from the cortex via MLVs. We assume that PBM-mediated relaxation of the lymphatic vessels can be possible mechanisms underlying increasing the permeability of the lymphatic endothelium that allows molecules transported by the lymphatic vessels and explain PBM stimulation of lymphatic drainage and clearance. These findings open new strategies for the stimulation of MLVs functions and non-pharmacological therapy of brain diseases.
The recently rediscovered meningeal lymphatic system (MLS) opens new insight into pathways of brain clearing and drainage functions that play an important role in neurorehabilitation. The development of breakthrough strategies for augmentation of MLS might be a promising therapeutic target for preventing of neurological diseases. Here we demonstrate photostimulation (PS, 1268 nm) of clearing and drainage function of MLS in healthy male mice. We uncover PS‐mediated increase of the mesenteric lymphatic permeability to fluorescent macrophages via a decrease of expression of tight junction and transendothelial resistance. In sum, our results clearly show PS stimulation of meningeal clearing and drainage functions as well as effects of PS on permeability of the lymphatic endothelium to macrophages. These findings open new strategies for alternative nonpharmacological therapy of brain diseases via PS modulation of lymphatic mechanisms of the homeostasis of central nervous system.
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.
The blood-brain barrier (BBB) has a significant contribution to the protection of the central nervous system (CNS). However, it also limits the brain drug delivery and thereby complicates the treatment of CNS diseases. The development of safe methods for an effective delivery of medications and nanocarriers to the brain can be a revolutionary step in the overcoming this limitation. Here, we report the unique properties of the lymphatic system to deliver tracers and liposomes to the brain meninges, brain tissues, and glioma in rats. Using a quantum-dot-based 1267 nm laser (for photosensitizer-free generation of singlet oxygen), we clearly demonstrate photostimulation of lymphatic delivery of liposomes to glioma as well as lymphatic clearance of liposomes from the brain. These pilot findings open promising perspectives for photomodulation of lymphatic delivery of drugs and nanocarriers to the brain pathology bypassing the BBB. The lymphatic “smart” delivery of liposomes with antitumor drugs in the new brain tumor branches might be a breakthrough strategy for the therapy of gliomas.
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