Photodynamic opening of the blood‐brain barrier and pathways of brain clearing

Abstract

A new application of the photodynamic treatment (PDT) is presented for the opening of blood-brain barrier (BBB) and the brain clearing activation that is associated with it, including the use of gold nanoparticles as emerging photosensitizer carriers in PDT. The obtained results clearly demonstrate 2 pathways for the brain clearing: (1) using PDT-opening of BBB and intravenous injection of FITC-dextran we showed a clearance of this tracer via the meningeal lymphatic system in the subdural space; (2) using optical coherence tomography and intraparenchymal injection of gold nanorods, we observed their clearance through the exit gate of cerebral spinal fluid from the brain into the deep cervical lymph node, where the gold nanorods were accumulated. These data contribute to a better understanding of the cerebrovascular effects of PDT and shed light on mechanisms, underlying brain clearing after PDT-related opening of BBB, including clearance from nanoparticles as drug carriers.

Photodynamic therapy of brain tumors and novel optical coherence tomography strategies for in vivo monitoring of cerebral fluid dynamics

“…We used two methods for the BBB openingthe sound that induces the mild BBB opening and PDT causing the strong BBB leakage with the accumulation of extensive°uids in the PVS. 106,107 Indeed, using confocal imaging of dextran extravasation and spectro°uorimetric assay of Evans Blue albumin complex level in the brain tissues, we showed opening of the BBB for these tracers that was more pronounced in the PDT group vs. the sound group. These changes stimulated the brain drainage with an increase in the volume of cerebral spinal°uid (CSF) in the cisterna magna that was also more pronounced in the PDT group vs. the sound group.…”

“…The FITC-dextran injected intravenously immediately is observed in the Sagittal sinus (the main cerebral vein) and after PDT-opening of the BBB it is also presented in the meningeal lymphatic vessels due to activation of clearance of FITC-dextran from the brain parenchyma. 107 molecule-A and PECAM-1/CD31. 111,112 The opening of the BBB is accompanied by disbalance in expression of indicated proteins 113 that can in°uent the complex of these proteins in the lymphatic system.…”

Loud music and the specific sound stress open the blood-brain barrier: new fundamental, biomedical, and social aspects

“…31 Assessment of apoptosis, brain histology and neurobehavioral pattern did not reveal excessive apoptosis, morphological alterations in the brain tissues and vessels, or hearing loss and cognitive impairment in mice in 1h after sound exposure when BBB was opened and in 4h/24h after sound exposure when BBB integrity was fully restored. The reversibility of sound-induced BBB breakdown might be linked to the activation of the brain drainage and clearing systems via the meningeal lymphatic pathway after BBB opening 43,44 . In our recent work, we discovered an important role of the meningeal lymphatic systems in the brain clearing from substances, which permeate from blood into the brain parenchyma through opened BBB induced by sound or photodynamic effects.…”

“…In our recent work, we discovered an important role of the meningeal lymphatic systems in the brain clearing from substances, which permeate from blood into the brain parenchyma through opened BBB induced by sound or photodynamic effects. 43,44 iii. Does sound open BBB directly or via stress?…”

Lymphatic Meningeal Role in Processes of Brain Clearing: in vivo Visualization

“…Глубокий шейный лимфатический узел является первой анатомической станцией выхода спинномозговой жидкости из мозга, что было показано в исследованиях на животных и людях [17][18][19].…”