PT  - JOURNAL ARTICLE
AU  - Humberto Mestre
AU  - Benjamin T. Kress
AU  - Wenyan Zou
AU  - Tinglin Pu
AU  - Giridhar Murlidharan
AU  - Ruth M. Castellanos Rivera
AU  - Matthew J. Simon
AU  - Martin M. Pike
AU  - Benjamin A Plog
AU  - Anna L. R. Xavier
AU  - Alexander S. Thrane
AU  - Iben Lundgaard
AU  - John H. Thomas
AU  - Ming Xiao
AU  - Aravind Asokan
AU  - Jeffrey J. Miff
AU  - Maiken Nedergaard
TI  - Aquaporin-4 dependent glymphatic solute transport in rodent brain
AID  - 10.1101/216499
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 216499
4099  - http://biorxiv.org/content/early/2017/11/09/216499.short
4100  - http://biorxiv.org/content/early/2017/11/09/216499.full
AB  - The 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.