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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Neurol. Mar 28, 2016; 6(1): 1-13
Published online Mar 28, 2016. doi: 10.5316/wjn.v6.i1.1
Aquaporin-4 and spinal cord injury
Jennifer M Yonan, Devin K Binder
Jennifer M Yonan, Devin K Binder, Neuroscience Graduate Program, University of California at Riverside, Riverside, CA 92521, United States
Devin K Binder, Division of Biomedical Sciences, School of Medicine, Center for Glial-Neuronal Interactions, Riverside, CA 92521, United States
Author contributions: Yonan JM performed all literature reviews, analysis and drafting of this paper; Binder DK provided critical revisions, editing and approval of the final version.
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Devin K Binder, MD, PhD, Division of Biomedical Sciences, School of Medicine, Center for Glial-Neuronal Interactions, Neuroscience Graduate Program, University of California at Riverside, 1247 Webber Hall, Riverside, CA 92521, United States. dbinder@ucr.edu
Telephone: +1-951-8272224 Fax: +1-951-8275504
Received: September 26, 2015
Peer-review started: October 6, 2015
First decision: November 24, 2015
Revised: December 25, 2015
Accepted: January 16, 2016
Article in press: January 19, 2016
Published online: March 28, 2016
Processing time: 181 Days and 11.9 Hours
Abstract

Edema formation is a major problem following traumatic spinal cord injury (SCI) that acts to exacerbate secondary damage. Severity of edema correlates with reduced neurological outcome in human patients. To date, there are no effective treatments to directly resolve edema within the spinal cord. The aquaporin-4 (AQP4) water channel is found on membranes of astrocytic endfeet in direct contact with blood vessels, the glia limitans in contact with the cerebrospinal fluid and ependyma around the central canal. Being so locally expressed at the interface between fluid and tissue allow AQP4 channels to play an important role in the bidirectional regulation of water homeostasis under normal conditions and following trauma. With the need to better understand the pathophysiology underlying the devastating cellular events in SCI, animal models have become an integral part of exploration. Inevitably, several injury models have been developed (contusion, compression, transection) resulting in difficult interpretation between studies with conflicting results. This is true in the case of understanding the role of AQP4 in the progression and resolution of edema following SCI, whose role is still not completely understood and is highly dependent on the type of edema present (vasogenic vs cytotoxic). Here, we discuss regulation of AQP4 in varying injury models and the effects of potential therapeutic interventions on expression, edema formation and functional recovery. Better understanding of the precise role of AQP4 following a wide range of injuries will help to understand optimal treatment timing following human SCI for prime therapeutic benefit and enhanced neurological outcome.

Keywords: Spinal cord injury; Astrocyte; Aquaporin-4; Edema; Water channel

Core tip: Edema formation is a major problem following spinal cord injury (SCI) that acts to exacerbate secondary damage. Animal models have become an integral part of understanding this pathophysiology. Several SCI models have been developed, resulting in difficult interpretation between studies with conflicting results. This is true for the role of aquaporin-4 (AQP4) water channels in the development and resolution of edema following SCI. Here, we discuss regulation of AQP4 in varying models and the effect of current interventions on expression, edema formation and functional recovery. Understanding the precise role of AQP4 will help to determine optimal treatments following human SCI.