Transcranical photobiomodulation (tPBM, 1267 nm, 32 J/cm2) is effective non-invasive method for clearance of beta-amyloid from the brain in mice with Alzheimer’s disease and for improvemen of their neurological status.
Here in ex vivo (confocal imaging) and in vivo (optical coherent tomography) experiments on adult mice, we clearly demonstrate that the meningeal lymphatic drainage is an important mechanism for the brain clearing that might be also pathway for the brain clearing from metabolites and waste products that requests further detailed studies. Photodynamic effects stimulate the meningeal/cervical drainage opening new ideas for development of novel methods of activation of brain clearing that might be progressive strategies in therapy of neurovegetative diseases.
In our experiments on rats we performed visualization of brain clearing from substances injected into the brain parenchyma using optical coherent tomography and fluorescence microscopy. Our results uncovered that the meningeal lymphatic system play an important role in the brain clearing processes, where the deep cervical lymph node is the first anatomical station of cerebral fluid exist from the brain. These data shed light on the novel mechanisms underlying drainage and clearing function of the brain.
Here we present preliminary experimental data suggesting about involvement of the meningeal and cervical lymphatics in neurorehabilitation. Using model of hemorrhagic stroke, immunohistochemical analysis and atomic absorption spectroscopy, we clearly demonstrate the lymphatic clearance from the blood after stroke via the meningeal lymphatic vessels with further accumulation of hemosiderin and iron (products of disaggregated hemoglobin) in the deep cervical node (dcLN). The optical coherent tomography (OCT) was used for in vivo monitoring of accumulation of gold nanorods (92 nm in diameter) in the dcLN after their injection into the cisterna magna with the aim of mimicking of the brain clearance from of blood. The both ex vivo and in vivo data show the lymphatic clearance from subjects (the blood/GNRs) injected into the subarachnoid space that might be an important mechanism of neurorehabilitation after the intracranial hemorrhages.
The development of novel technologies for the imaging of meningeal lymphatic vessels is one of the amazing trends of biophotonics thanks to discovery of brain lymphatics over several years ago. However, there is the limited technologies exist for the study of lymphatics in vivo because lymphatic vessels are transparent with a low speed flow of lymph. Here we demonstrate the successful application of fluorescent microscopy for the imaging of lymphatic system in the mouse brain in vivo.
Here we studied the role of cerebral lymphatic system in the brain clearing using intraparenchymal injection of Evans Blue and gold nanorods assessed by optical coherent tomography and fluorescence microscopy. Our data clearly show that the cerebral lymphatic system plays an important role in the brain cleaning via meningeal lymphatic vessels but not cerebral veins. Meningeal lymphatic vessels transport fluid from the brain into the deep cervical node, which is the first anatomical “station” for lymph outflow from the brain. The lymphatic processes underlying brain clearing are more slowly vs. peripheral lymphatics. These results shed light on the lymphatic mechanisms responsible for brain clearing as well as interaction between the intra- and extracranial lymphatic compartment.
The meningeal lymphatic vessels were discovered 2 years ago as the drainage system involved in the mechanisms underlying the clearance of waste products from the brain. The blood–brain barrier (BBB) is a gatekeeper that strongly controls the movement of different molecules from the blood into the brain. We know the scenarios during the opening of the BBB, but there is extremely limited information on how the brain clears the substances that cross the BBB. Here, using the model of sound-induced opening of the BBB, we clearly show how the brain clears dextran after it crosses the BBB via the meningeal lymphatic vessels. We first demonstrate successful application of optical coherence tomography (OCT) for imaging of the lymphatic vessels in the meninges after opening of the BBB, which might be a new useful strategy for noninvasive analysis of lymphatic drainage in daily clinical practice. Also, we give information about the depth and size of the meningeal lymphatic vessels in mice. These new fundamental data with the applied focus on the OCT shed light on the mechanisms of brain clearance and the role of lymphatic drainage in these processes that could serve as an informative platform for a development of therapy and diagnostics of diseases associated with injuries of the BBB such as stroke, brain trauma, glioma, depression, or Alzheimer disease.
Chronic hypertension itself does not cause stroke but significantly decreases the resistant to stroke induced by
stress due to exhausting of adaptive capacity of cerebral endothelium and decrease resistance of blood-brain
barrier to stress.
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