In this pilot study, we analyzed effects of transcranial photobiomodulation (tPBM, 1267 nm, 32 J/cm2) 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/cm2) 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 meningeal lymphatic system that was recently discovered is a network of optically transparent vessels that play a vital role in the health of the central nervous system (CNS) in protecting the brain against pathogens.1–3 In 2015, Louveau et al.1 and Aspelund et al.2 clearly showed that the meningeal lymphatic system is involved in the clearing of waste products from the brain.
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.
Electrospinning is a well-established method for the fabrication of polymer biomaterials, including those with core-shell nanofibers. The variability of structures presents a great range of opportunities in tissue engineering and drug delivery by incorporating biologically active molecules such as drugs, proteins, and growth factors and subsequent control of their release into the target microenvironment to achieve therapeutic effect. The object of study is non-woven core-shell PVA–PEG–SiO2@PVA–GO fiber mats assembled by the technology of coaxial electrospinning. The task of the core-shell fiber development was set to regulate the degradation process under external factors. The dual structure was modified with silica nanoparticles and graphene oxide to ensure the fiber integrity and stability. The influence of the nano additives and crosslinking conditions for the composite was investigated as a function of fiber diameter, hydrolysis, and mechanical properties. Tensile mechanical tests and water degradation tests were used to reveal the fracture and dissolution behavior of the fiber mats and bundles. The obtained fibers were visualized by confocal fluorescence microscopy to confirm the continuous core-shell structure and encapsulation feasibility for biologically active components, selectively in the fiber core and shell. The results provide a firm basis to draw the conclusion that electrospun core-shell fiber mats have tremendous potential for biomedical applications as drug carriers, photocatalysts, and wound dressings.
21 January 2020 in Journal of Innovative Optical Health Sciences
Photodynamic therapy (PDT) is a promising tool for least-invasive alternative methods for the treatment of brain tumors. The newly discovered PDT-induced opening of the blood–brain barrier (BBB) permeability open novel strategies for drug-brain delivery during post-surgical treatment of glioblastoma GBM. Here we discuss mechanisms of PDT-mediated opening of the BBB and age differences in PDT-related increase in BBB permeability, including with formation of brain edema. The meningeal lymphatic system plays a crucial role in the mechanism of brain drainage and clearance from metabolites and toxic molecules. We discuss that noninvasive photonic stimulation of fluid clearance via meningeal lymphatic vessels, and application of optical coherence tomography (OCT) for bed-side monitoring of meningeal lymphatic drainage has the promising perspective to be widely applied in both experimental and clinical studies of PDT and improving guidelines of PDT of brain tumors.