Aquaporin-4 and spinal cord injury

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.