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.
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.
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.
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. However, further development of the tumor (formation of the necrotic core) led to decrease in the water content. The dependence of the scattering properties on the different stages of model glioma development was more complex. Light penetration depth into the healthy and tumor brain was evaluated.
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