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Publication : Aquaporin-4-dependent glymphatic solute transport in the rodent brain.

First Author  Mestre H Year  2018
Journal  Elife Volume  7
PubMed ID  30561329 Mgi Jnum  J:277304
Mgi Id  MGI:6330865 Doi  10.7554/eLife.40070
Citation  Mestre H, et al. (2018) Aquaporin-4-dependent glymphatic solute transport in the rodent brain. Elife 7:e40070
abstractText  The glymphatic system is a brain-wide clearance pathway; its impairment contributes to the accumulation of amyloid-beta. 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.
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