glymphatic clearance; glymphatic flow (glymphatic system)

Introduction

The term glymphatic derives from its resemblance to the peripheral lymphatic system & the participation of perivascular glial cells (glial-lymphatic -> glymphatic)

Function

• term used in reference to glia-assisted disposal of waste products into the CSF through perivascular spaces for distribution to the systemic circulation (see CSF)
• glymphatic clearance peaks in mice when they sleep
  • aquaporin receptors are more highly expressed in sleep
  • interstitial spaces themselves expand
• glymphatic clearance is active in humans
• in humans, slow-wave sleep leads to reductions in cerebral blood volume, increases in interstitial fluid, & increased flow of CSF into the ventricles
• pulsatility of the brain's arteries creates a convective force that draws CSF into the brain from the space around its arterial walls & back out again along its veins, facilitating penetration of CSF into the brain parenchyma
• vasoactive intestinal peptide interneurons facilitate glymphatic clearance by regulating arterial pulsatility
• aquaporins (aquaporin-4) line outer wall of glymphatic vessels along with flat end feet of specialized astrocytes
• the inner wall of glymphatic vessels are the outer walls of brain arteries & veins
• the aquaporins (aquaporin-4) allow passage of CSF (arterioles) & interstitial fluid (venules) across the outer glymphatic walls
• large oscillations of CSF inflow into the brain appear ~ every 20 seconds tightly coupled to fMRI signals of blood flow & EEG slow waves
• CSF exchanges with brain parenchymal interstitial fluid, percolating through & around astroglial end-feet toward nearby venules, along which it then exits the brain thus taking with it neuronal waste products
• the veins must propel the waste CSF-interstitial fluid toward the arachnoid villi where it is absorbed into the systemic circulation
• the process is termed glymphatic clearance
• waste products such as beta-amyloid & other aggregation-prone proteins are cleared not only alongside veins but also across the blood-brain barrier into the systemic circulation
• besides waste elimination, the glymphatic system also facilitates brain-wide distribution of glucose, lipids, amino acids, growth factors, & neuromodulators

Pathology

• impaired glymphatic clearance may exacerbate microglial inflammatory response in Alzheimer's disease

Comparative biology

• 40 Hz (gamma) stimulation promotes influx of CSF & efflux of interstitial fluid in the cortex of a mouse model of Alzheimer's disease
  • influx of CSF was associated with increased aquaporin-4 polarization along astrocytic endfeet & dilation of meningeal lymphatic vessels
  • removal of beta-amyloid by glymphatic clearance was enhanced by gamma stimulation

More general terms

• clearance

Additional terms

• MRI brain perivascular spaces