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Elife. 2017 Aug 21;6. pii: e27679. doi: 10.7554/eLife.27679.

Test of the 'glymphatic' hypothesis demonstrates diffusive and aquaporin-4-independent solute transport in rodent brain parenchyma.

Smith AJ1,2, Yao X1,2, Dix JA1,2, Jin BJ1,2, Verkman AS1,2.

Author information

1
Department of Medicine, University of California, San Francisco, San Francisco, United States.
2
Department of Physiology, University of California, San Francisco, San Francisco, United States.

Abstract

Transport of solutes through brain involves diffusion and convection. The importance of convective flow in the subarachnoid and paravascular spaces has long been recognized; a recently proposed 'glymphatic' clearance mechanism additionally suggests that aquaporin-4 (AQP4) water channels facilitate convective transport through brain parenchyma. Here, the major experimental underpinnings of the glymphatic mechanism were re-examined by measurements of solute movement in mouse brain following intracisternal or intraparenchymal solute injection. We found that: (i) transport of fluorescent dextrans in brain parenchyma depended on dextran size in a manner consistent with diffusive rather than convective transport; (ii) transport of dextrans in the parenchymal extracellular space, measured by 2-photon fluorescence recovery after photobleaching, was not affected just after cardiorespiratory arrest; and (iii) Aqp4 gene deletion did not impair transport of fluorescent solutes from sub-arachnoid space to brain in mice or rats. Our results do not support the proposed glymphatic mechanism of convective solute transport in brain parenchyma.

KEYWORDS:

CSF; aquaporin 4; convection; diffusion; extracellular space; glymphatic hypothesis; mouse; neuroscience; rat

PMID:
28826498
PMCID:
PMC5578736
DOI:
10.7554/eLife.27679
[Indexed for MEDLINE]
Free PMC Article

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