n this
Spotlight, we introduce the glymphatic system: the brain's dedicated waste
clearance system. Now implicated in various conditions, it is high time that we
became acquainted.
Many
of us are relatively familiar with the lymphatic system; it performs a number
of roles, one of which is clearing metabolic waste from the gaps between cells,
referred to as the interstitial space.
However,
the central nervous system (CNS),
which comprises the brain and spinal cord, does not have any true lymphatic vessels.
Because
the CNS is highly active, metabolic waste can build up quickly.
The
CNS is also very sensitive to fluctuations in its environment, so the body
needs to remove cellular garbage somehow, and that's where the glymphatic
system comes in.
Before
the discovery of this brain-based garbage disposal system, scientists believed
that each individual cell handled its own metabolic detritus.
If
the cellular system became overloaded or slowed down as we aged, metabolic
garbage would build up between the cells. This garbage includes products such
as beta-amyloid — the protein associated with Alzheimer's disease.
Astroglia
The
term "glymphatic" was coined by Maiken Nedergaard,
a Danish neuroscientist who discoveredthe
system. The name is a reference to the glial cells, which are vital to this
waste clearance system.
Glial
cells get relatively little coverage, compared with neurons, despite being just
as numerous in
the brain. They were long considered little more than lowly support cells, but
are now held in higher regard.
Glia
protect, nourish, and insulate neurons. They also play a role in the immune
system and, as we now know, the glymphatic system.
In
particular, a type of glial cell known as astroglia are important. Receptors,
called aquaporin-4 channels, on these cells allow cerebrospinal fluid (CSF) to
move into the CNS, setting up a current that shunts fluid through the system.
CSF
is a clear fluid that surrounds the CNS, providing it with mechanical and
immunological protection, among other things.
The glymphatic system, which runs parallel to arteries,
also harnesses the pulsing of blood in circulation to help keep things moving.
As
the blood vessels expand rhythmically, they drive the exchange of compounds
between the interstitial space and the CSF.
The
glymphatic system connects with the lymphatic system of the rest of the body at
the dura, a thick membrane of connective tissue that covers the CNS.
The
importance of sleep
Following
Nedergaard's discovery, she ran a series of experiments on mice to develop a
better understanding of how this system worked and when it was most active. In
particular, the team focused on sleep and Alzheimer's.
Nedergaard
and her team found that the glymphatic system was most busy as the animals
slept. They showed that the volume of interstitial space increased by 60% while
the mice were sleeping.
This
volume increase also boosted the exchange of CSF and interstitial fluid,
speeding up the removal of amyloid. They concluded that:
"The restorative function of sleep may be a
consequence of the enhanced removal of potentially neurotoxic waste products
that accumulate in the awake [CNS]."
This
early work inspired a wave of new studies, the most recent of which was published this
month. The researchers looked at the impact of high blood pressure on
the function of the glymphatic system.
Over
time, high blood pressure causes blood vessels to lose their elasticity, becoming
increasingly stiff. Because the regular pulsing of arterial walls drives the
glymphatic system, this stiffening impedes its function.
Using a
mouse model of hypertension, the
scientists demonstrated that high blood pressure-induced artery stiffening did
interfere with the way that the garbage disposal system worked; it prevented it
from efficiently getting rid of large molecules in the brain, such as
beta-amyloid.
This
finding might help explain why scientists have found links between elevated blood pressureand cognitive
decline and dementia.
Source: Medical News Today
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