Protective role of aquaporin-4 water channels after contusion spinal cord injury.
OBJECTIVE
Spinal cord injury (SCI) is accompanied by disruption of the blood-spinal cord barrier and subsequent extravasation of fluid and proteins, which results in edema (increased water content) at the site of injury. However, the mechanisms that control edema and the extent to which edema impacts outcome after SCI are not well elucidated.


METHODS
Here, we examined the role of aquaporin-4 (AQP4) water channels after experimental contusion injury in mice, a clinically relevant animal model of SCI.


RESULTS
Mice lacking AQP4 (AQP4(-/-) mice) exhibited significantly impaired locomotor function and prolonged bladder dysfunction compared with wild-type (WT) littermates after contusion SCI. Consistent with a greater extent of functional deterioration, AQP4(-/-) mice showed greater neuronal loss and demyelination, with prominent cyst formation, which is generally absent in mouse SCI. The extent of spinal cord edema, as expressed by percentage water content, was persistently increased above control levels in AQP4(-/-) mice but not WT mice at 14 and 28 days after injury. Immunohistochemical analysis indicated that blood vessels in the vicinity of the lesion core had incomplete barrier function because of sparse tight junctions.


CONCLUSIONS
These results suggest that AQP4 plays a protective role after contusion SCI by facilitating the clearance of excess water, and that targeting edema after SCI may be a novel therapeutic strategy.
Department of Neurological Surgery, University of California, Irvine, CA, USA.
Atsushi
A
Kimura
Mike
M
Hsu
Marcus
M
Seldin
Alan S
AS
Verkman
Helen E
HE
Scharfman
Devin K
DK
Binder
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051401:Aquaporin 4 / Q000172:deficiency / Q000378:metabolism*; D004195:Disease Models, Animal; D004487:Edema / Q000209:etiology; D005353:Fibronectins / Q000378:metabolism; D020287:In Situ Nick-End Labeling / Q000379:methods; D008124:Locomotion / Q000187:drug effects / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009069:Movement Disorders / Q000209:etiology; D011597:Psychomotor Performance / Q000502:physiology; D020127:Recovery of Function / Q000235:genetics; D013119:Spinal Cord Injuries / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors; D001745:Urinary Bladder Diseases / Q000209:etiology
C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D005353:Fibronectins