Clearing the Waste : How the Brain does it

Hippocratus (460- 370BC) had alluded to a water channel that encircles the brain. But  it took  2000+ years for scientists  to  put together, piece by piece, a detailed  picture highlighting  its  physiological significance.  Thus now we refer to  the clear liquid  that "waters" the brain and spinal cord as  the cerebro-spinal fluid, CSF for short. Specialised  ependymal cells   in the inner cavity of the brain produce this liquid in  pulses.  Chemically   CSF is very much like  serum but with one major difference.  The Protein content in serum could be as high as 7000mg/dL, whereas CSF registers only about 35mg/dL.  We also know that CSF fulfils  multiple responsibilities in the brain, such as cushioning the brain, preserving its buoyancy, supplying nutrients   and   scavenging  waste.  The  complex network of channels through which CSF flows, together with  its associated  glial (neuronal) cells,  is collectively known as  the Glymphatic System.   As recent as in  in 2015, scientists spotted lymphatic vessels in the meninges too.  Meninges is  the three tiered protective  cover that shields   the brain and the spinal cord. It is now realised that the menengeal lymphatic  system  closely collaborates with the glymphatic system in waste removal from the brain.   

Courtesy: Wikipedia 

The CSF sweeps up the waste  and later  gets  partly absorbed into the venous circulation and partly   drained into the lymphatic system for downstream processing.  In young healthy adults, this process is rapid and regular.  But with age the process becomes sluggish and waste gets accumulated. A typical case in study is the Alzheimer's disease,  in which  amyloid plaques accumulate. This  debris in turn  interferes with and impairs neuronal function and also clogs the drainage pathway.  Of course it could as well be a combination of over-production of amyloid plaques and under performance of the clearance system.

Scientists were indeed astonished to find that the  glymphatic system is mostly dormant when we are awake and gets into fully active mode only when we are asleep.  Using sophisticated imaging techniques, it has been  demonstrated that the rate of waste clearance from the brain  increases by about 60% during the sleep cycle. Hence the extrapolation by Xie et al   that  the restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system. Scientists are exploring  the possibility of clearing the choked pathways as a novel approach for  managing  neurodegenerative diseases such as  Alzheimer's. 

Tailpiece:

It has been found that healthy bones  facilitate the production of  osteocalcin, a hormone necessary for memory retention.  Prof.Eric Kandel,    who received  Nobel Prize in 2000 for unravelling the neurological pathways of learning and memory, has this to say:  "If you walk two or three miles a day, you will release sufficient osteocalcin from your bones to combat non-Alzheimer's, age-related memory loss"

REFERENCES:

1. Works by Hippocrates

2. The discovery of Cerebrospinal fluid

3. Studies on the cerebra-Spinal Fluid : Cushing(1914)

4. Quantifying CNS protein production and clearance rates in humans.... Bateman et  al

5. Sleep drives Metabolite clearance from the adult brain
6. Iconic Neuroscientist Eric Kandel Shares This Advice for Combating Memory Loss