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

Abstract

We report here a pilot identification of the presence of the lumenized Lyve-1/Prox-1-expressing vessels with distinct walls composed of a single endothelial layer in the unaffected brain and with intraventricular hemorrhages. These lymphatic vessels (LVs) have valves and an undulating shape in the distal region that is the classical characteristic of lymphatic precollectors. Furthermore, we identified Lyve-1/Prox-1-expressing lymphatic elements in the enlarged perivascular spaces. These pioneering results might be a revolutionary step in our understanding of anatomy and physiology of the cerebral lymphatics and stimulate a reassessment of basic assumptions in the aetiology of brain diseases associated with lymphatic dysfunction. The discovery of the cerebral LVs is a crucial step in the development of breakthrough technologies of modulations of lymphatic removing of toxins and blood from the brain.

A Long-Acting Lyotropic Liquid Crystalline Implant Promotes the Drainage of Macromolecules by Brain-Related Lymphatic System in Treating Aged Alzheimer’s Disease

“…Meanwhile, with the deeper understanding of brain-related lymphatic networks, a number of studies were committed to delivering drugs to the brains by deep cervical lymph nodes (dCLNs) bypassing the blood–brain barrier (BBB), which also inspired our interests. − As a result, we designed a long-acting injectable lyotropic liquid crystalline implant encapsulating both cilostazol and donepezil hydrochloride (an FDA-approved symptomatic relief agent for AD), which was delivered by dCLNs. By injecting a drug-loaded platform into dCLNs, we found that brain-entering efficiency of both drugs was elevated when compared with oral and subcutaneous delivery, confirming the therapeutic advantage of this delivery route.…”

Promising Strategies to Reduce the SARS-CoV-2 Amyloid Deposition in the Brain and Prevent COVID-19-Exacerbated Dementia and Alzheimer’s Disease

“…Because MLVs play an important role in draining brain tissues and removing toxins and metabolites from the brain, future treatments for reversible forms of dementia are expected to involve stimulation of lymphatic drainage processes. Given the growing evidence of the existence of lymphatic vessels directly in the human brain [ 292 , 293 , 294 , 295 ], and not only in its meninges [ 296 , 297 ], technologies for activating lymphatic drainage processes will contribute to progress in the treatment of a wide number of brain diseases associated with dysfunction of the cerebral lymphatic system, such as AD, Parkinson’s disease, brain trauma and oncology [ 44 , 45 , 46 , 47 , 48 , 49 , 118 , 119 , 162 , 275 , 276 ].…”

Technology of the photobiostimulation of the brain’s drainage system during sleep for improvement of learning and memory in male mice

“…Nevertheless, over two centuries, scientific evidence has accumulated providing the presence of drainage processes in the CNS [ 1 , 3 ]. It is still unknown whether LVs exist directly in the CNS [ 4 , 5 ]. However, the presence of LV in the brain’s meninges is widely accepted [ 6 , 7 ].…”