I have often heard that the cerebrospinal fluid (CSF) and interstitial fluid (ISF) are in free exchange. Because the CSF eventually drains (predominantly) into the dural venous sinuses, ISF's ability to access the subarachnoid space actually allows the brain to eliminate metabolic waste products that would otherwise remain the parenchyma. ISF presumably accesses the subarachnoid space, mixes with the CSF, and eventually, through arachnoid granulations, drains via the dural sinuses.

While that is fine and dandy...there are two layers that the ISF must first pass in order to access the subarachnoid space: the glial limitans and the pia mater.

How does ISF pass through the foot processes of astrocytes, which comprise the glial limitans? Does the H2O remain largely in the parenchyma while waste metabolites are selectively transported across the astrocytes and into the small spaces between the glial limitans and pia mater?


1 Answer 1


Excellent question. This is an active area of research.

The glia limitans defines the external most layer of brain parenchyma. Previously thought to primarily be a barrier against migration and growth of neural cells out of the brain parenchyma during development, recent work has characterized its involvement in regulating the immune environment of the CNS. A 2017 JCI paper demonstrated that the tight junctions of the glia limitans are inducible in mouse in response to inflammatory cues. You may find the associated editorial helpful. In addition to demonstrating a dynamic role for the barrier function, you can see that tight junctions are not the standard state, and the typical state allows passive diffusion as well as active transport of small molecules between the CSF and brain ISF, but the question is not fully resolved.

Importantly, this is mouse data, and mouse data in particular cannot fully resolve questions about human astrocytes.


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