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. Interpretation: 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. ANN NEUROL 2010;67:794-801