THE GLYMPHATIC SYSTEM AND ITS THERAPEUTIC IMPLICATIONS IN NEUROLOGICAL DISEASES

Resumo

Introduction: The glymphatic system (GS) is present in the Central Nervous
System (CNS) and it is analogous to the lymphatic system, present in other regions
of the human body. It works by a convective flow of cerebrospinal fluid (CSF) into
the interstitial space (IS) through transmembrane channels of aquaporin 4 (AQP4),
which are expressed in cerebral astrocytes. SG is a recent discovery, making it
necessary to describe its mechanism and applicability in neurological diseases.
Objectives: To discuss the GS and its role in the pathophysiological understanding
of neurological diseases and its possible implications in the diagnostic and
therapeutic research. Methods: A literature review was conducted during the
month of September 2017 in the databases of PubMed and Lilacs, with the following
keywords: glymphatic system, neurodegenerative diseases and sleep. Discussion:
This GS acts like a cleaning method for the interstitial fluid (IF) and extracellular
solutes (ES) from the CNS. It works mainly during the sleep, in which its clearance of
the cerebral metabolites is more effective. During the wake period, it works the
opposite way due to the low noradrenaline acting in the process of expansion and
contraction of the IS. The CSF enters the cerebral parenchyma through paraarterial
routes along with the IF, which carry ES from the IS to be drained by paravenous
exit routes. The AQP4 channels in the astrocytes surrounding the cerebral
vasculature facilitate the cleaning of soluble proteins, metabolism products and
excess extracellular fluid. The fundamental elements of GS - paraarterial and
paravenous vascularization, convective flow of CSF and IF, astrocytes and AQP4 -
can be altered by physiological or pathological degeneration. Aging promotes the
gliosis of the astrocytes, the AQP4 channels lose their polarization and the
paraarterial and paravenous vessels become stiffer, factors that make the GS more
susceptible to accumulation of metabolites, such as ?-amyloid. The decrease
activity and accumulation of protein aggregates is primordial for the development of
neurodegenerative diseases (Parkinson's, Alzheimer's). This correlation may serve
as a target for therapeutic management and diagnostic tests that may early identify
a decline in GS activity. Finally, traumatic brain injuries and strokes are known to be
correlated with increased neurodegenerative diseases due to the transient
accumulation of protein entanglements, which reduces the activity of the GS. Thus,
inhibiting the suppression of the GS in these situations may contribute to decrease
the severity of brain injury and future complications. Conclusion: The role of GS in
pathology of neurological diseases is evident, as well as its relationship with early
diagnosis, as shown by studies with neuroimaging that could detect the degree of
GS function through contrast infusion in the cisterna magna.