[Epub ahead of print]

Aquaporins in brain edema.

Tifenn Clément, Beatriz Rodriguez-Grande, Jérôme Badaut
J Neuro Res. 2018-11-15; :
DOI: 10.1002/jnr.24354

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Aquaporins in brain edema.

Clément T(1), Rodriguez-Grande B(1), Badaut J(1)(2).

Author information:
(1)CNRS UMR 5287, INCIA, University of Bordeaux, Bordeaux, France.
(2)Department of Basic Science, Loma Linda University School of Medicine, Loma
Linda, California.

Brain edema is a common feature of brain injuries, which leads to increased
intracranial pressure (ICP) and ischemia that worsen outcome. Current management
of edema focuses on reduction of ICP, but there are no treatments targeting the
molecular players directly involved in edema process. The perivascular astrocyte
endfeet are critical in maintaining brain homeostasis with ionic and water
exchange; in this context, aquaporins (AQPs), astrocyte water channels, have
emerged as privileged targets for edema modulation. However, AQPs can facilitate
either accumulation or drainage of water, depending on the osmotic gradients
between extra-intracellular space; and thus inhibition of AQPs leads to different
outcomes depending on specific tissue characteristics and time post-injury. Most
of this knowledge has been gathered from the study of AQP4, the best
characterized AQP and the one that has the biggest impact on water movement. In
addition to the level of expression, the ratio of AQP4 isoforms (m1, m23 or mz),
the spatial distribution of AQP4 into orthogonal arrays of particles, and the
interaction of AQP4 with neighboring ionic channels and gap junctions could
directly impact edema formation. Although there are no specific AQP4
pharmacological blockers, the development of AQP4 siRNA offers a promising
therapeutic tool. Given the complex dynamics of AQP4, therapies targeting AQP4
should carefully take into account the particular features of the injury (e.g.,
hemorrhagic vs. non-hemorrhagic) and different times after injury (e.g., phase of
edema formation vs. resolution).

© 2018 Wiley Periodicals, Inc.

DOI: 10.1002/jnr.24354
PMID: 30430614

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