Abstract
The glymphatic system is a glial-dependent waste clearance pathway in the central nervous system, devoted to drain away waste metabolic products and soluble proteins such as amyloid-beta. An impaired brain glymphatic system can increase the incidence of neurovascular, neuroinflammatory, and neurodegenerative diseases. Photobiomodulation (PBM) therapy can serve as a non-invasive neuroprotective strategy for maintaining and optimizing effective brain waste clearance. In this review, we discuss the crucial role of the glymphatic drainage system in removing toxins and waste metabolites from the brain. We review recent animal research on the neurotherapeutic benefits of PBM therapy on glymphatic drainage and clearance. We also highlight cellular mechanisms of PBM on the cerebral glymphatic system. Animal research has shed light on the beneficial effects of PBM on the cerebral drainage system through the clearance of amyloid-beta via meningeal lymphatic vessels. Finally, PBM-mediated increase in the blood–brain barrier permeability with a subsequent rise in Aβ clearance from PBM-induced relaxation of lymphatic vessels via a vasodilation process will be discussed. We conclude that PBM promotion of cranial and extracranial lymphatic system function might be a promising strategy for the treatment of brain diseases associated with cerebrospinal fluid outflow abnormality.
Highlights
Photobiomodulation (PBM) therapy is the application of visible and near-infrared (NIR) light to stimulate cellular processes by changing biochemical activities of mitochondrial components at non-thermal and low-level doses [1]
The results revealed that PBM can promote migration of macrophages from the lymphatic vessels into surrounding tissues, most likely through the decrease in transendothelial electrical resistance (TEER) integrity and an expression of tight junction (TJ) proteins (e.g., CLND, VE-cadherin, and ZO-1) [87]
Using immunohistochemical and confocal colocalization analysis of the mouse and human brain samples, they showed that red blood cells (RBCs) moved from the ventricles into deep cLNs (dcLNs) via MLVs, confirming the lymphatic clearance of RBCs from the brain in the post-hemorrhagic period
Summary
Photobiomodulation (PBM) therapy is the application of visible and near-infrared (NIR) light to stimulate cellular processes by changing biochemical activities of mitochondrial components at non-thermal and low-level doses [1]. Starting from 2018, a group of researchers from Russia has made efforts to test the modulatory actions of PBM therapy on the lymphatic drainage function of the brain Their preliminary findings in a mouse AD model shed light on the potential effect of NIR PBM on the cerebral drainage system through the clearance of Aβ via MLVs [15]. Their follow-up studies revealed that a PBM-mediated increase in the blood–brain barrier (BBB) permeability can result in further activation of the lymphatic clearance of Aβ from the brain. Studies on mouse models using different fluorescent tracers constructed this glymphatic drainage pathway in the brain [23,24] This system consists of five main functional components, each facilitating the movement of CSF and ISF (Figure 1). The glymphatic system has been described as the “final common pathway” for neurodegenerative diseases [36]
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