Pilot study of transcranial photobiomodulation of lymphatic clearance of beta-amyloid from the mouse brain: breakthrough strategies for non-pharmacologic therapy of Alzheimer’s disease

Abstract

In this pilot study, we analyzed effects of transcranial photobiomodulation (tPBM, 1267 nm, 32 J/cm 2 ) on clearance of beta-amyloid (Aβ) from the mouse brain. The immunohistochemical and confocal data clearly demonstrate the significant reduction of deposition of Aβ plaques in mice after tPBM vs. untreated animals. The behavior tests showed that tPBM improved the cognitive, memory and neurological status of mice with Alzheimer's disease (AD). Using of our original method based on optical coherence tomography (OCT) analysis of clearance of gold nanorods (GNRs) from the brain, we proposed possible mechanism underlying tPBM-stimulating effects on clearance of Aβ via the lymphatic system of the brain and the neck. These results open breakthrough strategies for a non-pharmacological therapy of Alzheimer's disease and clearly demonstrate that tPBM might be a promising therapeutic target for preventing or delaying Alzheimer's disease.

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

“…Due to a good penetration of PS into the brain cortex, tPS can stimulate MLVs. In our recent pilot study on mice with the injected AD model, we have clearly demonstrated that 9 days course of tPS (1267 nm, 32 J/cm 2 ) strongly reduces Aβ plaques in the brain which is associated with improving of the memory and neurocognitive deficit [63]. Based on our data on the real time monitoring of lymphatic clearance of gold nanorods (GNRs) from the cortex, the hyppocampus, the right ventricle, and the cisterna magna, we have proposed that the tPS-mediated stimulation of lymphatic drainage might be a possible mechanism underlying the tPS-elimination of Aβ from the brain.…”

“…The transcranial photostimulation (tPS) is considered as a possible novel nonpharmacological and non-invasive promising strategy for prevention or delay of AD [63]- [69], depression [70]- [75], Parkinson's disease [76], stroke [77], [78], traumatic brain injuries [79], [80], post-mastectomy lymphedema [81], [82], and post-surgical swelling [82]- [84]. The PS, known as low-level laser therapy, was first proposed by Endre Mester in 1967 for stimulation of hair growth [85] and in 1971 for wound healing [86].…”

“…Zhao et al demonstrate that injection of fluorescent nanoparticles subcutaneously close to dcLNs is accompanied by nanoparticles brain delivery through the meningeal lymphatic vessels (MLVs) [62]. [63]; the choroid cells injected into acupuncture point ST36 transfer to the striatum, the choroid plexus and the substantia nigra [61].…”

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

“…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].…”

Trapping of Magnetic Nanoparticles in the Blood Stream under the Influence of a Magnetic Field

“…The motivation for this theoretical study is a design of robust algorithms needed to evaluate parameters of magnetically-driven systems for a particular biomedical application with actual complexity and real geometry, such as magnetic drug delivery and treatment [1][2][3][4][5][6][7], monitoring and control of brain tissue cleansing from metabolites and toxins, activation of brain drainage function [9], magnetomotive OCT for imaging nanomolar concentrations of magnetic nanoparticles in tissues [10], magnetomotive DOCT for imaging of melanoma-implanted magnetic nanoparticles [11], and magnetomotive laser speckle imaging [12].…”