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

In this pilot study, we analyzed effects of transcranial photobiomodulation (tPBM, 1267 nm, 32 J/cm2) 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

Optical in vivo and ex vivo imaging of glioma cells migration via the cerebral vessels: Prospective clinical application of the beta2-adrenoreceptors blockade for glioma treatment

Malignant gliomas are highly invasive tumors that use the cerebral vessels for invasion due to high vascular fragility of the blood–brain barrier (BBB). On one hand, glioma is characterized by the BBB disruption, on the other hand, drug brain delivery via the BBB is a big challenge in glioma therapy. The limited information about vascular changes associated with glioma growth is a reason of slow progress in prevention of glioma development. Here, we present in vivo and ex vivo study of the BBB disruption and glioma cells (GCs) migration in rats using fluorescence and confocal microscopy. We uncovered a local breach in the BBB in the main tumor mass but not within the border of normal and malignant cells, where the BBB was impermeable for high weight molecules. The migration of GCs were observed via the cerebral vessels with the intact BBB that was associated with macrophages infiltration. The mechanisms underlying glioma progression remain unknown but there is an evidence that the sympathetic nervous system (SNS) via activation of vascular beta2-adrenoreceptors (B2-ADRs) can play an important role in tumor metastasis. Our results clearly show an increase in the expression of vascular B2-ADRs and production of the beta-arrestin-1 — co-factor of B2-ADRs signaling pathway in rats with glioma. Pharmacological blockade of B2-ADRs reduces the BBB disruption, macrophages infiltration, GCs migration and increases survival rate. These data suggest that the blockade of B2-ADRs may be a novel adjuvant therapeutic strategy to reduce glioma progression and prevent metastasis