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

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.

The effect of photobiomodulation on the brain during wakefulness and sleep

“…The precise mechanisms used by photobiomodulation to stimulate the activity of the glymphatic system, that is to improve the fluid clearance and disposal of waste-products from the brain, are far from clear ( Salehpour et al, 2022 ). Previous authors have shown that photobiomodulation prompts the breakdown of various protein aggregations within the brain and stimulates a nitric oxide-induced vasodilation – at least outside the brain, within the lymphatic vessels of the meninges – and these are likely to contribute to the improved fluid and waste clearance from the brain ( Yue et al, 2019 ; Semyachkina-Glushkovskaya et al, 2020 , 2021a , 2021b , 2021c ).…”

“…Semyachkina-Glushkovskaya and colleagues suggest that the fluid clearance of the brain is promoted further by photobiomodulation-induced vasodilation of the meningeal lymphatic vessels, and this mechanism may help the process also ( Semyachkina-Glushkovskaya et al, 2020 , 2021a , 2021b , 2021c ). Further, photobiomodulation may also effect the composition of cerebrospinal fluid, by changing the structure of the water molecules, making the cerebrospinal fluid more free flowing ( Salehpour et al, 2022 ). In addition, the flow of the cerebrospinal fluid may be influence by the cilia lining the ventral parts of the third ventricle which are considered to be under circadian control ( Eichele et al, 2020 ); photobiomodulation may have a considerable influence this system as well.…”

Transcranial near-infrared light in treatment of neurodegenerative diseases

“…The presence of NO in local vascular and lymphatic circulation as a result of this stimulation leads to vasodilation, promotes free, unobstructed flow of blood and lymphatic fluid, gas exchange, and overall brain circulation through vascular and lymphatic systems ( Ahmed et al, 2011 ; Semyachkina-Glushkovskaya et al, 2021a ). Improved flow-through brain lymphatics also support immune function in the brain, improve immune cell exchange rate in chronic inflammatory conditions and promote better anti-inflammatory properties of innate immunity ( Salehpour et al, 2022 ).…”

“…Both are well-reported pro-inflammatory enzyme and pro-inflammatory gene expression cascades, respectively ( Lim et al, 2013 ). In addition, PBM stimulation also helps manage innate immune response by regulating other pro-inflammatory cytokines and improves lymphatic fluids flow in brain lymphatic and glymphatic drainage systems ( Semyachkina-Glushkovskaya et al, 2020a ; Salehpour et al, 2022 ).…”

Lymphatic system in the brain

“…The impaired glial cell-dependent waste clearance pathway of the central nervous system (CNS) gives rise to neurovascular, neurodegenerative, and neuroinflammatory disorders [ 11 ]. Glymphatic disorder, perhaps connected to aquaporin-4 water channels (AQP4) expression, has been demonstrated in disorders such as Alzheimer's disease (AD), stroke and traumatic condition, and head injury [ 5 ].…”