@article{8129110d342f48d3be158ef517c7a3d7,
title = "Aquaporin-4-dependent glymphatic solute transport in the rodent brain",
abstract = "The glymphatic system is a brain-wide clearance pathway; its impairment contributes to the accumulation of amyloid-β. Influx of cerebrospinal fluid (CSF) depends upon the expression and perivascular localization of the astroglial water channel aquaporin-4 (AQP4). Prompted by a recent failure to find an effect of Aqp4 knock-out (KO) on CSF and interstitial fluid (ISF) tracer transport, five groups re-examined the importance of AQP4 in glymphatic transport. We concur that CSF influx is higher in wild-type mice than in four different Aqp4 KO lines and in one line that lacks perivascular AQP4 (Snta1 KO). Meta-analysis of all studies demonstrated a significant decrease in tracer transport in KO mice and rats compared to controls. Meta-regression indicated that anesthesia, age, and tracer delivery explain the opposing results. We also report that intrastriatal injections suppress glymphatic function. This validates the role of AQP4 and shows that glymphatic studies must avoid the use of invasive procedures.",
author = "Humberto Mestre and Hablitz, {Lauren M.} and Xavier, {Anna L.R.} and Weixi Feng and Wenyan Zou and Tinglin Pu and Hiromu Monai and Giridhar Murlidharan and Rivera, {Ruth M.Castellanos} and Simon, {Matthew J.} and Pike, {Martin M.} and Virginia Pl{\'a} and Ting Du and Kress, {Benjamin T.} and Xiaowen Wang and Plog, {Benjamin A.} and Thrane, {Alexander S.} and Iben Lundgaard and Yoichiro Abe and Masato Yasui and Thomas, {John H.} and Ming Xiao and Hajime Hirase and Aravind Asokan and Iliff, {Jeffrey J.} and Maiken Nedergaard",
note = "Funding Information: This study was funded by the NIH (NS100366, NS078394, NS089709, NS061800, AG048769, AG054456, AG054093, NS099371 and HL089221), NNSF81671070, the Knut and Alice Wallenberg Foundation, Western Norway Regional Health Authority (Helse Vest). RIKEN Center for Brain Science (formerly, RIKEN Brain Science Institute), KAKENHI grants (18K14859 to HM, 16H01888 and 18H05150 to HH, 17K19637 and 16H05134 to YA, 18H02606 to MY), HFSP (RGP0036/2014 to HH), JSPS Core-to-Core Program: A Advanced Research Networks, HH is a recipient of the Lundbeck Foundation Visiting Professorship. We thank Dan Xue for expert graphic illustrations, Hayley Martin for assistance with meta-analysis, Amanda M Sweeney and Genaro E Olveda for expert technical assistance, and Paul Cumming for comments on the manuscript.Japan Society for the Promotion 18K14859 Hiromu Monai of ScienceKnut och Alice Wallenbergs Helse Vet Alexander S Thrane Stiftelse Japan Society for the Promotion 17K19637 Yoichiro Abe of Science Japan Society for the Promotion 16H05134 Yoichiro Abe of Science Japan Society for the Promotion 18H02606 Masato Yasui of Science National Institute on Aging RF1 AG057575-01 John H Thomas Maiken Nedergaard Japan Society for the Promotion 16H01888 Hajime Hirase of ScienceJapan Society for the Promotion 18H05150 Hajime Hirase of ScienceHuman Frontier Science Program RGP0036/2014 Hajime Hirase Japan Society for the Promotion Core-to-Core Program Hajime Hirase of ScienceLundbeckfonden Visiting Professorship Hajime Hirase National Institutes of Health NS061800 Aravind Asokan National Institutes of Health NS099371 Aravind AsokanNational Institutes of Health HL089221 Aravind AsokanNational Institutes of Health NS089709 Jeffrey J IliffNational Institutes of Health AG054456 Jeffrey J. IliffNational Institutes of Health NS100366 Maiken NedergaardNational Institutes of Health NS078394 Maiken NedergaardNational Institutes of Health AG048769 Maiken NedergaardDr. Miriam and Sheldon G. Maiken Nedergaard Adelson Medical Research Foundation EU Joint Programme – Neuro-degenerative 643417/DACAPO-AD Maiken Nedergaard Disease Research. Publisher Copyright: {\textcopyright} Mestre et al.",
year = "2018",
month = dec,
day = "1",
doi = "10.7554/eLife.40070",
language = "English",
volume = "7",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}