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

Abstract

Intraventricular hemorrhage (IVH) is the most fatal form of brain injury, yet a therapy directed at ameliorating intraventricular clot is very limited. There is accumulating evidence that an augmentation of the meningeal lymphatic (MLVs) functions might be a promising therapeutic target for IVH. In particular, the photostimulation (PS) of MLVs could be promising for non-invasive therapy of IVH via PS of clearance of red blood cells (RBCs) from the brain via MLVs. Indeed, we uncover that PS has therapeutic effects on IVH in mice reducing the mortality, improving the emotional status, accelerating the RBCs evacuation from the ventricles and increasing the ICP recovery. Our findings strongly suggest that the PS-mediated stimulation of drainage and clearing functions of MLVs can be a novel bedside, readily applicable and commercially viable technologies for treatment of IVH. These pilot results open new horizons in a non-invasive therapy of IVH via PS stimulation of regenerative lymphatic mechanisms.

Night Photostimulation of Clearance of Beta-Amyloid from Mouse Brain: New Strategies in Preventing Alzheimer’s Disease

“…In our previous works, we studied the mechanisms of the PS effects on the lymphatics. Our data demonstrate that PS induces relaxation of the lymphatic vessels, which is associated with an increase in the permeability of the lymphatic endothelium [ 30 , 31 , 32 , 35 ]. We show that a decrease in the transepithelial electrical resistance and in the expression of tight junction (TJ) proteins, such as CLDN-5, VE-cadherin, and ZO-1, might be a possible mechanism underlying a PS-mediated increase in the lymphatic permeability.…”

“…Therefore, we selected PS (1267 nm, 9 J/cm 2 ) for the modulation of the lymphatic clearance of Aβ from the brain. The choice of a PS dose of 9 J/cm 2 was based on our recent results demonstrating that PS at 9 J/cm 2 is an optimal dose for the stimulation of the lymphatic clearance of different tracers and red blood cells from the right lateral ventricle without the heating effect [ 35 ].…”

“…PS increases the lymphatic contractility [ 30 , 35 ] that is regulated by NO [ 62 , 63 ]. Our recent findings show that PS dilates the MLVs and increases NO production in the isolated lymphatic endothelial cells, which is associated with an increase in the lymphangion contraction [ 35 ].…”

“…We also demonstrated that the course of PS during 9 days effectively reduces the Aβ level in mice with AD [ 33 , 34 ]. There is evidence that PS modulates the tone and permeability of the lymphatic vessels, probably through PS-induced stimulation of the synthesis of nitric oxide (NO) in the lymphatic endothelium [ 26 , 27 , 28 , 29 , 35 ]. Thus, PS is a promising candidate as an effective tool for the stimulation of the lymphatic clearance of Aβ from the brain.…”

Pilot identification of the Live-1/Prox-1 expressing lymphatic vessels and lymphatic elements in the unaffected and affected human brain

“…To conclude, further studies of anatomy and functions of cerebral LVs, including traffic of immune cells, will be a revolutionary step in a reassessment of basic assumptions in neuroimmunology and the aetiology of brain diseases associated with a lymphatic system dysfunction. The discovery of the cerebral LVs is a crucial step in the development of breakthrough technologies of therapeutic modulation of lymphatic removing of blood and toxins from the brain that we revealed in our study on mice with a model of intraventricular hemorrhages (20).…”