Aquaporin and brain diseases

Badaut, Jérôme; Fukuda, Andrew M.; Jullienne, A.; Petry, Klaus G.

doi:10.1016/j.bbagen.2013.10.032

Cited by 181 publications

(159 citation statements)

References 129 publications

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“…Under physiological conditions, AQP4 is located strategically on astrocyte endfeet surrounding brain vasculature. 28 We show here that the absence of AQP4, beyond the regulation of water movements, affects the permeability of the BBB, with an attenuated leakage of immunoglobulins into the extracellular space in the absence of AQP4. However, we can not exclude that BBB dysfunction is still present in the AQP4 À/À , as it has been described at late time points after stroke in wild type rodents.…”

Section: Discussionmentioning

confidence: 99%

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

Hirt

Fukuda

Ambadipudi

et al. 2016

J Cereb Blood Flow Metab

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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 À/À mice and of AQP4 expression following stroke. Here, we studied AQP4 and its role in edema formation by testing AQP4À/À 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 À/À 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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Section: Discussionmentioning

confidence: 99%

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

Hirt

Fukuda

Ambadipudi

et al. 2016

J Cereb Blood Flow Metab

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“…The distribution of AQP4 is diverse throughout the brain, and includes the cerebral cortex, corpus callosum, retina, cerebellum, magnocellular nuclei of the hypothalamus, and brain stem [4]. AQP4 has a tetrametric structure, enabling gases and ions to permeate through a central pore; however, the physiological role of this central pore remains unclear [1].…”

Section: Introductionmentioning

confidence: 99%

Neuroimmunological Implications of AQP4 in Astrocytes

Ikeshima-Kataoka

2016

IJMS

116

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The brain has high-order functions and is composed of several kinds of cells, such as neurons and glial cells. It is becoming clear that many kinds of neurodegenerative diseases are more-or-less influenced by astrocytes, which are a type of glial cell. Aquaporin-4 (AQP4), a membrane-bound protein that regulates water permeability is a member of the aquaporin family of water channel proteins that is expressed in the endfeet of astrocytes in the central nervous system (CNS). Recently, AQP4 has been shown to function, not only as a water channel protein, but also as an adhesion molecule that is involved in cell migration and neuroexcitation, synaptic plasticity, and learning/memory through mechanisms involved in long-term potentiation or long-term depression. The most extensively examined role of AQP4 is its ability to act as a neuroimmunological inducer. Previously, we showed that AQP4 plays an important role in neuroimmunological functions in injured mouse brain in concert with the proinflammatory inducer osteopontin (OPN). The aim of this review is to summarize the functional implication of AQP4, focusing especially on its neuroimmunological roles. This review is a good opportunity to compile recent knowledge and could contribute to the therapeutic treatment of autoimmune diseases through strategies targeting AQP4. Finally, the author would like to hypothesize on AQP4’s role in interaction between reactive astrocytes and reactive microglial cells, which might occur in neurodegenerative diseases. Furthermore, a therapeutic strategy for AQP4-related neurodegenerative diseases is proposed.

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“…Several studies of vasogenic oedema models have demonstrated that bulk flow pathways, including white matter tracts and perivascular spaces, are important sites for oedema fluid movement and clearance (reviewed in [138]). Aquaporin water channels clearly play a role in the resolution of edema; in particular, AQP4 has been suggested to regulate ECS water in the healthy and diseased brain due to its localized expression on astrocytes at brain-CSF and blood-brain interfaces and demonstrated alterations in disease states [8].…”

Section: Cns Pathologies and Disturbances Of Brain Fluidsmentioning

confidence: 99%

The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system?

et al. 2018

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Brain fluids are rigidly regulated to provide stable environments for neuronal function, e.g., low K + , Ca 2+ , and protein to optimise signalling and minimise neurotoxicity. At the same time, neuronal and astroglial waste must be promptly removed. The interstitial fluid (ISF) of the brain tissue and the cerebrospinal fluid (CSF) bathing the CNS are integral to this homeostasis and the idea of a glia-lymph or 'glymphatic' system for waste clearance from brain has developed over the last 5 years. This links bulk (convective) flow of CSF into brain along the outside of penetrating arteries, glia-mediated convective transport of fluid and solutes through the brain extracellular space (ECS) involving the aquaporin-4 (AQP4) water channel, and finally delivery of fluid to venules for clearance along peri-venous spaces. However, recent evidence favours important amendments to the 'glymphatic' hypothesis, particularly concerning the role of glia and transfer of solutes within the ECS. This review discusses studies which question the role of AQP4 in ISF flow and the lack of evidence for its ability to transport solutes; summarizes attributes of brain ECS that strongly favour the diffusion of small and large molecules without ISF flow; discusses work on hydraulic conductivity and the nature of the extracellular matrix which may impede fluid movement; and reconsiders the roles of the perivascular space (PVS) in CSF-ISF exchange and drainage. We also consider the extent to which CSF-ISF exchange is possible and desirable, the impact of neuropathology on fluid drainage, and why using CSF as a proxy measure of brain components or drug delivery is problematic. We propose that new work and key historical studies both support the concept of a perivascular fluid system, whereby CSF enters the brain via PVS convective flow or dispersion along larger caliber arteries/arterioles, diffusion predominantly regulates CSF/ISF exchange at the level of the neurovascular unit associated with CNS microvessels, and, finally, a mixture of CSF/ISF/waste products is normally cleared along the PVS of venules/veins as well as other pathways; such a system may or may not constitute a true 'circulation', but, at the least, suggests a comprehensive re-evaluation of the previously proposed 'glymphatic' concepts in favour of a new system better taking into account basic cerebrovascular physiology and fluid transport considerations.

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Aquaporin and brain diseases

Cited by 181 publications

References 129 publications

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

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

Neuroimmunological Implications of AQP4 in Astrocytes

The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system?

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