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

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 neuronal survival and reduced neuroinflammation, but without a direct effect on edema formation.

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@article{Hirt2017ImprovedLO, title={Improved long-term outcome after transient cerebral ischemia in aquaporin-4 knockout mice.}, author={Lorenz Hirt and Andrew Minoru Fukuda and K. Ambadipudi and Faisil Rashid and Devin K. Binder and A . S . Verkman and Stephen Ashwal and Andre Obenaus and Jerome Badaut}, journal={Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism}, year={2017}, volume={37 1}, pages={277-290} }