Title:Current Understanding of Central Nervous System Drainage Systems: Implications in the Context of Neurodegenerative Diseases
Volume: 18
Issue: 11
Author(s): Vladimir N. Nikolenko , Marine V. Oganesyan, Angela D. Vovkogon, Arina T. Nikitina, Ekaterina A. Sozonova, Valentina A. Kudryashova, Negoria A. Rizaeva, Ricardo Cabezas, Marco Avila-Rodriguez, Margarita E. Neganova, Liudmila M. Mikhaleva, Sergey O. Bachurin, Siva G. Somasundaram, Cecil E. Kirkland, Vadim V. Tarasov and Gjumrakch Aliev*
Affiliation:
- Sechenov First Moscow State Medical University (Sechenov University), St. Trubetskaya, 8, bld. 2, Moscow, 119991,Russian Federation
Keywords:
Glymphatic system, meningeal lymphatic vessels (MLV), cerebrospinal fluid (CSF), blood-brain barrier (BBB),
functional anatomy, interstitial fluid of the brain, aquaporin-4, clinical perspective, neurodegenerative disorders.
Abstract: Until recently, it was thought that there were no lymphatic vessels in the central nervous
system (CNS). Therefore, all metabolic processes were assumed to take place only in the circulation
of the cerebrospinal fluid (CSF) and through the blood-brain barrier’s (BBB), which regulate ion
transport and ensure the functioning of the CNS. However, recent findings yield a new perspective:
There is an exchange of CSF with interstitial fluid (ISF), which is drained to the paravenous space
and reaches lymphatic nodes at the end. This circulation is known as the glymphatic system. The
glymphatic system is an extensive network of meningeal lymphatic vessels (MLV) in the basal area
of the skull that provides another path for waste products from CNS to reach the bloodstream. MLV
develop postnatally, initially appearing around the foramina in the basal part of the skull and the
spinal cord, thereafter sprouting along the skull’s blood vessels and spinal nerves in various areas of
the meninges. VEGF-C protein (vascular endothelial growth factor), expressed mainly by vascular
smooth cells, plays an important role in the development of the MLV. The regenerative potential
and plasticity of MLV and the novel discoveries related to CNS drainage offer potential for the
treatment of neurodegenerative diseases such as dementia, hydrocephalus, stroke, multiple sclerosis,
and Alzheimer disease (AD). Herein, we present an overview of the structure and function of the
glymphatic system and MLV, and their potential involvement in the pathology and progression of
neurodegenerative diseases.
