scholarly journals CrossTalk opposing view: Going against the flow: interstitial solute transport in brain is diffusive and aquaporin‐4 independent

2019 ◽  
Vol 597 (17) ◽  
pp. 4421-4424 ◽  
Author(s):  
Alex J. Smith ◽  
Alan S. Verkman
Keyword(s):  
Solute Transport ◽  
Aquaporin 4 ◽  
Opposing View ◽  
Interstitial Solute

scholarly journals Author response: Aquaporin-4-dependent glymphatic solute transport in the rodent brain

2018 ◽  
Author(s):  
Humberto Mestre ◽  
Lauren M Hablitz ◽  
Anna LR Xavier ◽  
Weixi Feng ◽  
Wenyan Zou ◽  
...  
Keyword(s):  
Solute Transport ◽  
Aquaporin 4 ◽  
Author Response ◽  
Rodent Brain

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

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Alex J Smith ◽  
Xiaoming Yao ◽  
James A Dix ◽  
Byung-Ju Jin ◽  
Alan S Verkman
Keyword(s):  
Solute Transport ◽  
Fluorescence Recovery After Photobleaching ◽  
Gene Deletion ◽  
Brain Parenchyma ◽  
Convective Transport ◽  
Aquaporin 4 ◽  
Rodent Brain ◽  
Clearance Mechanism ◽  
Solute Movement ◽  
Photon Fluorescence

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.

scholarly journals Aquaporin-4 dependent glymphatic solute transport in rodent brain

2017 ◽  
Author(s):  
Humberto Mestre ◽  
Benjamin T. Kress ◽  
Wenyan Zou ◽  
Tinglin Pu ◽  
Giridhar Murlidharan ◽  
...  
Keyword(s):  
Solute Transport ◽  
Healthy Aging ◽  
Fluid Transport ◽  
Water Channel ◽  
Amyloid Β ◽  
Aquaporin 4 ◽  
Tau Proteins ◽  
Glymphatic System ◽  
Aqp4 Expression ◽  
Transgenic Lines

AbstractThe glymphatic system is a brain-wide metabolite clearance pathway, impairment of which in post-traumatic and ischemic brain or healthy aging is proposed to contribute to intracerebral accumulation of amyloid-β and tau proteins. Glymphatic perivascular influx of cerebrospinal fluid (CSF) depends upon the expression and perivascular localization of the astroglial water channel aquaporin-4 (AQP4). Prompted by a recent publication that failed to find an effect of Aqp4 knockout on perivascular CSF tracer influx and interstitial fluid (ISF) tracer dispersion, four independent research groups have herein re-examined the importance of Aqp4 in glymphatic fluid transport. We concur in finding that CSF tracer influx, as well as fluorescently-tagged amyloid-β efflux, are significantly faster in wild-type mice than in three different transgenic lines featuring disruption of the Aqp4 gene and one line in which AQP4 expression lacks the critical perivascular localization (Snta1 knockout). These data validate the role of AQP4 in supporting fluid and solute transport and efflux in brain in accordance with the glymphatic system model.

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