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Review
. 2013 Jun;44(6 Suppl 1):S93-5.
doi: 10.1161/STROKEAHA.112.678698.

Is there a cerebral lymphatic system?

Jeffrey J Iliff  1 , Maiken Nedergaard
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Review

Is there a cerebral lymphatic system?

Jeffrey J Iliff et al. Stroke. .
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Figures

Figure 1. Schematic of glymphatic pathway function in normal and diseased brain
Conceptual framework for the failure of glymphatic interstitial solute clearance after diffuse injury. (A) In the healthy brain, CSF from the subarachnoid space rapidly enters the brain along paravascular channels surrounding penetrating arteries (green arrow) and exchanges with brain ISF. ISF and solutes are cleared to paravascular spaces surrounding large caliber draining veins (orange arrows). Convective bulk fluid flux between the paravascular CSF influx and ISF efflux pathways is facilitated by astroglial water transport through AQP4 expressed exclusively along perivascular astrocytic endfeet. This convective bulk flow facilitates the clearance of interstitial solutes from the brain. (B) Reactive astrogliosis that occurs after diffuse injury such as microinfarction or mild traumatic brain injury causes in the mis-localization of AQP4 from the perivascular endfeet to the rest of the astrocytic soma. This results in the loss of efficient interstitial bulk flow, and the failure of glymphatic interstitial solute clearance and may contribute to the deposition of extracellular and intracellular protein aggregates (such as amyloid β or tau) after diffuse injury.
Figure 2. Changes in AQP4 localization after diffuse injury
(A) Immunofluorescent double-labeling demonstrates that in the healthy young mouse brain, AQP4 expression is highly localized to perivascular astrocytic endfeet surrounding to entirety of the cerebral microvasculature. (B) 7 days after mild traumatic brain injury, widespread reactive astrogliosis (GFAP-immunoreactivity) is observed throughout the ipsilateral cortex. In regions of reactive astrogliosis, AQP4 localization is severely perturbed, exhibiting a loss of polarization to the endfoot process and increased somal labeling. Similar expression patters are observed after diffuse microinfarction (manuscript under review).
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