NO-ergic mechanisms of age differences in photostimulation of lymphatic drainage, filtration, and clearance
Year: 2025
Type: article
Abstract: Photobiomodulation (PBM) is recognized as a promising, noninvasive, and safe therapy for brain diseases. However, age is a limiting factor for effective phototherapy of brain pathology. The mechanisms of decreasing efficiency of therapeutic effects of PBM in the aging brain remain poorly understood. Recently, it has been shown that PBM of brain lymphatic drainage by stimulation of the nitric oxide (NO) production in the lymphatic endothelium plays a key role in the PBM-therapy of brain diseases. In this study, we clearly show that PBM increases the NO production in the lymphatic endothelial cells and the contractility of the afferent (drainage function) and efferent (filtration function) cervical lymphatic vessels (cLVs), which is significantly suppressed after the NO blockade in 3- and 12-month-old mice. However, 24-month-old mice are insensitive to both factors, PBM and its suppression by the NO blockade. In old mice, a decrease in sensitivity to PBM is associated with age-related lymphatic endothelium dysfunction, including changes in the cLV morphology (hyperplasia), a decrease in the NO production, and the contractility of cLVs, leading to reduced lymphatic removal of beta amyloid from the brain. These results suggest that the combined therapy, including PBM with an increase in NO production in the lymphatic endothelium, can substantially improve the effectiveness of the stimulating effects of PBM on brain drainage and the removal of toxic metabolites from its tissues, which might generally contribute to improving phototherapy of brain diseases in the elderly.
Source: Biomedical Optics Express
DOI: 10.1364/boe.577347
Authors: Anastasiia Semyichkina-Glushkovskaia, Inna Blokhina, Ivan Fedosov, Alexander Shirokov, Maria Tsoy, Alexander Dubrovsky, Alexander Dmitrenko, Andrey Terskov, Daria Zlatogorskaya, Viktoria Adushkina, Arina Evsukova, Matvey Tuzhilkin, Inna Elizarova, Anastasiia Kalabukhova, Egor Ilyukov, Dmitry Myagkov, Dmitry Tuktarov, Sergey Popov, Timophey Inozemcev, Oxana Semyachkina-Glushkovskaya, Jürgen Kurths
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,913
Funder: Russian Science Foundation
Awards: G3118492505, G785604369
OpenAlex ID: W4415568712