Photostimulation of Extravasation of Beta-Amyloid through the Model of Blood-Brain Barrier

Abstract

Alzheimer’s disease (AD) is an incurable pathology associated with progressive decline in memory and cognition. Phototherapy might be a new promising and alternative strategy for the effective treatment of AD, and has been actively discussed over two decades. However, the mechanisms of therapeutic photostimulation (PS) effects on subjects with AD remain poorly understood. The goal of this study was to determine the mechanisms of therapeutic PS effects in beta-amyloid (Aβ)-injected mice. The neurological severity score and the new object recognition tests demonstrate that PS 9 J/cm2 attenuates the memory and neurological deficit in mice with AD. The immunohistochemical assay revealed a decrease in the level of Aβ in the brain and an increase of Aβ in the deep cervical lymph nodes obtained from mice with AD after PS. Using the in vitro model of the blood-brain barrier (BBB), we show a PS-mediated decrease in transendothelial resistance and in the expression of tight junction proteins as well an increase in the BBB permeability to Aβ. These findings suggest that a PS-mediated BBB opening and the activation of the lymphatic clearance of Aβ from the brain might be a crucial mechanism underlying therapeutic effects of PS in mice with AD. These pioneering data open new strategies in the development of non-pharmacological methods for therapy of AD and contribute to a better understanding of the PS effects on the central nervous system.

Photobiomodulation Therapy and the Glymphatic System: Promising Applications for Augmenting the Brain Lymphatic Drainage System

“…Recently, a group of researchers from Russia have carried out a series of animal studies on the possible beneficial effects of PBM therapy on the lymphatic drainage function of the brain [ 15 , 16 , 59 , 84 , 85 , 86 , 87 ]. Their findings have opened up a new idea that PBM of the cranial and the extracranial lymphatics may be a promising approach for the treatment of brain disorders associated with CSF outflow abnormality [ 88 ].…”

“…In the fourth study, they aimed to test the hypothesis that the PBM-mediated opening of BBB might be one possible mechanism for the activation of Aβ clearance from the brain in AD mice [ 16 ]. First, they studied the effects of 1267 nm PBM with a cortical fluence of 9 J/cm 2 (skull fluence of 32 J/cm 2 ) on Aβ clearance from the mice brain using the immunohistochemical analysis of Aβ in the dcLNs.…”

“…Their findings uncovered the lymphatic pathway of Aβ clearance from the brain which was also associated with the enhancement of the neurobehavioral status in AD mice. Their follow-up experiments showed that a PBM-mediated increase in the BBB permeability and subsequent increase in Aβ leakage occurs most likely as a result of PBM-induced decrease in transendothelial integrity and decrease in the expression of TJ proteins (e.g., CLND, VE-cadherin, and ZO-1) [ 16 ].…”

“…Their follow-up studies also 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. This action is most likely a result of PBM-induced relaxation of lymphatic vessels via a vasodilation process [ 16 ]. Further experiments outlined the beneficial effects of NIR PBM on the lymphatic clearance of blood products from the brain, an important strategy for the prevention of severe consequences after intracranial hemorrhage (ICH) [ 17 ].…”

Transcranial near-infrared light in treatment of neurodegenerative diseases

“…Tissue stimulation with NIR light has demonstrated secretion of vascular endothelial growth factor in the endothelial cells leading to angiogenesis and the formation of capillary-like structures ( Tuby et al, 2006 ; Cury et al, 2013 ). Animal studies have also demonstrated that treatment with transcranial NIR (tNIR) light stimulates the brain’s glymphatic system flow, which promotes brain parenchymal homeostasis and clearance of excessive accumulation of metabolites along with protein aggregates from both deep and superficial brain regions in normal and different pathological conditions ( Zinchenko et al, 2019 ; Zinchenko et al,2020 ; Semyachkina-Glushkovskaya et al, 2021b ; Xuan et al, 2022 ; Zhang et al, 2022 ).…”