Photobiomodulation of lymphatic drainage and clearance: perspective strategy for augmentation of meningeal lymphatic functions

Abstract

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.

Photostimulation of lymphatic clearance of red blood cells from the mouse brain after intraventricular hemorrhage

“…As reported in our previous studies of PS-mediated stimulation of meningeal lymphatic clearance and drainage function, the 1267-nm laser in a dose of 9-10 J/cm 2 (17 min of laser irradiation, 5-min pause, 61 min in total) is effective for lymphatic clearance of small and large molecules from the brain into dcLNs [33, 34, 39]. Based on our pervious animal data and the established PS protocol [33, 34, 39], we investigated the effect of PS on MLVs using a 1267-nm laser with an indicated above dose. We uncovered that although IVH seemed to widen the diameter distribution of MLVs, it didn’t make significant difference on the average diameter (25.8±18.2 μm vs 25.75±15.7 μm).…”

“…The PS-mediated stimulation of the lymphatic drainage and clearing function might be one mechanisms playing an important role of PS in neurorehabilitation [32]. It has been proved that PS can regulate the relaxation and permeability of the mesenteric lymphatic vessels, activate moving of immune cells in the lymph, and has effectiveness in the management of lymphedema [33][34][35]. In our preliminary work, we clearly demonstrated that the near-infrared PS (1267 nm) stimulates clearance of tracers from the brain via MLVs after opening of the blood-brain barrier (BBB) or after its intracerebral injection [33,34,[36][37][38].…”

“…It has been proved that PS can regulate the relaxation and permeability of the mesenteric lymphatic vessels, activate moving of immune cells in the lymph, and has effectiveness in the management of lymphedema [33–35]. In our preliminary work, we clearly demonstrated that the near-infrared PS (1267 nm) stimulates clearance of tracers from the brain via MLVs after opening of the blood-brain barrier (BBB) or after its intracerebral injection [33, 34, 36–38]. We also showed that PS (1267 nm) effectively stimulates lymphatic clearance of beta-amyloid from the brain [39].…”

Biophotonic Strategies of Measurement and Stimulation of the Cranial and the Extracranial Lymphatic Drainage Function

“…We investigated possible mechanisms of tPS-stimulation of lymphatic drainage and clearance [88], [89]. Our results demonstrate that already low PS doses (1267 nm, 5 and 10 J/cm 2 ) cause relaxation of the mesenteric LVs and increase their permeability to fluorescent macrophages via a decrease of expression of the tight junction proteins and the transendothelial resistance.…”

“…However the detection of the lymphatic perfusion is not a trivial procedure that currently can be performed only with very specific animal models like the rat intestine mesentery lymphatic [88], [89] or the mouse ear skin [165]- [170], but no label-free detection of the lymph flow through MLVs has been reported yet. Both of these models represent the peripheral lymphatic system and provide the advantage of intravital optical imaging of the LVs structure and function [161], [168].…”