Improved long-term outcome after transient cerebral ischemia in aquaporin-4 knockout mice

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Lorenz HirtJerome Badaut

Abstract

A hallmark of stroke is water accumulation (edema) resulting from dysregulation of osmotic homeostasis. Brain edema contributes to tissue demise and may lead to increased intracranial pressure and lethal herniation. Currently, there are only limited treatments to prevent edema formation following stroke. Aquaporin 4 (AQP4), a brain water channel, has become a focus of interest for therapeutic approaches targeting edema. At present, there are no pharmacological tools to block AQP4. The role of AQP4 in edema after brain injury remains unclear with conflicting results from studies using AQP4-/- mice and of AQP4 expression following stroke. Here, we studied AQP4 and its role in edema formation by testing AQP4-/- mice in a model of middle cerebral artery occlusion using novel quantitative MRI water content measurements, histology and behavioral changes as outcome measures. Absence of AQP4 was associated with decreased mortality and increased motor recovery 3 to 14 days after stroke. Behavioral improvement was associated with decreased lesion volume, neuronal cell death and neuroinflammation in AQP4-/- compared to wild type mice. Our data suggest that the lack of AQP4 confers an overall beneficial role at long term with improved neur...Continue Reading

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Citations

Aug 17, 2016·International Journal of Molecular Sciences·Heling ChuQiang Dong
Mar 10, 2017·Brain Research Bulletin·Jacqueline A HubbardDevin K Binder
Oct 27, 2017·Expert Opinion on Therapeutic Targets·Alan S VerkmanMarc O Anderson
Nov 16, 2018·Journal of Neuroscience Research·Tifenn ClémentJérôme Badaut
Jan 3, 2019·American Journal of Physiology. Cell Physiology·Helena W Morrison, Jessica A Filosa
Oct 8, 2019·Brain and Behavior·Syuichi Tetsuka
Aug 29, 2020·Acta Pharmacologica Sinica·Zheng-Wei LuoHong-Shuo Sun
Jun 28, 2018·Frontiers in Molecular Neuroscience·Yu-Feng Wang, Vladimir Parpura
May 18, 2019·Proceedings of the National Academy of Sciences of the United States of America·Hiromu MonaiHajime Hirase
Aug 28, 2020·Acta Neuropathologica Communications·Wenhui HuangAnja Scheller
Jun 12, 2020·Frontiers in Cell and Developmental Biology·Irina FilchenkoLorenz Hirt
Jan 8, 2021·International Journal of Legal Medicine·Mizuho NosakaToshikazu Kondo
Mar 8, 2021·Experimental Neurology·Caihong JiAnwen Shao
May 1, 2021·International Journal of Molecular Sciences·Adjanie PatabendigeRuoli Chen
Jul 27, 2021·Frontiers in Aging Neuroscience·Tao LvXiaohua Zhang

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Methods Mentioned

BETA
confocal microscopy

Software Mentioned

ARRIVE
Matlab
Mercator

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