Interaction between blood-brain barrier and glymphatic system in solute clearance

Apr 3, 2018Neuroscience and biobehavioral reviews

How the Brain’s Protective Barrier and Waste-Removal System Work Together to Clear Substances

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Abstract

Disruption of waste clearance mechanisms in the brain may lead to protein accumulation associated with neurodegenerative disorders.

The brain vasculature plays a crucial role in clearing waste, including proteins like amyloid-β.
Cerebrospinal fluid exchange with interstitial fluid is facilitated by aquaporin-4 water channels in the glymphatic system.
Both blood-brain barrier transport and glymphatic clearance may work together to maintain a healthy neuronal environment.
Disruption of these clearance mechanisms could initiate neurodegenerative disorders such as Alzheimer's disease.
Future health initiatives aimed at improving waste clearance may help delay or prevent the onset of neurodegenerative disorders.
Imaging techniques to define glymphatic flow kinetics could potentially identify individuals at risk for Alzheimer's disease.

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Neurovascular pathology concurs with protein accumulation, as the brain vasculature is important for waste clearance. Interstitial solutes, such as amyloid-β, were previously thought to be primarily cleared from the brain by blood-brain barrier transport. Recently, the glymphatic system was discovered, in which cerebrospinal fluid is exchanged with interstitial fluid, facilitated by the aquaporin-4 water channels on the astroglial endfeet. Glymphatic flow can clear solutes from the interstitial space. Blood-brain barrier transport and glymphatic clearance likely serve complementary roles with partially overlapping mechanisms providing a well-conditioned neuronal environment. Disruption of these mechanisms can lead to protein accumulation and may initiate neurodegenerative disorders, for instance amyloid-β accumulation and Alzheimer's disease. Although both mechanisms seem to have a similar purpose, their interaction has not been clearly discussed previously. This review focusses on this interaction in healthy and pathological conditions. Future health initiatives improving waste clearance might delay or even prevent onset of neurodegenerative disorders. Defining glymphatic flow kinetics using imaging may become an alternative way to identify those at risk of Alzheimer's disease.

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Interaction between blood-brain barrier and glymphatic system in solute clearance

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