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

AJ Smith, X Yao, JA Dix, BJ Jin, AS Verkman - elife, 2017 - elifesciences.org
AJ Smith, X Yao, JA Dix, BJ Jin, AS Verkman
elife, 2017elifesciences.org
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 …
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.
eLife