Aquaporin-4 Expression in Post-Traumatic Syringomyelia

Abstract

Aquaporin-4 (AQP4) is an astroglial water channel protein that plays an important role in the transmembrane movement of water within the central nervous system. AQP4 has been implicated in numerous pathological conditions involving abnormal fluid accumulation, including spinal cord edema following traumatic injury. AQP4 has not been studied in posttraumatic syringomyelia, a condition that cannot be completely explained by current theories of cerebrospinal fluid dynamics. Alterations of AQP4 expression or function may contribute to the fluid imbalance leading to syrinx formation or enlargement. The aim of this study was to examine AQP4 expression levels and distribution in an animal model of posttraumatic syringomyelia. Immunofluorescence and western blotting were used to assess AQP4 and glial fibrillary acidic protein (GFAP) expression in an excitotoxic amino acid/arachnoiditis model of post-traumatic syringomyelia in SpragueDawley rats. At all time-points, GFAP-positive astrocytes were observed in tissue surrounding syrinx cavities, although western blot analysis demonstrated an overall decrease in GFAP expression, except at the latest stage investigated. AQP4 expression was significantly higher at the level of syrinx at three and six weeks following the initial syrinx induction surgery. Significant increases in AQP4 expression also were observed in the upper cervical cord, rostral to the syrinx except in the acute stage of the condition at the three-day time-point. Immunostaining showed that AQP4 was expressed around all syrinx cavities, most notably adjacent to a mature syrinx (six-and 12-week time-point). This suggests a relationship between AQP4 and fluid accumulation in post-traumatic syringomyelia. However, whether this is a causal relationship or occurs in response to an increase in fluid needs to be established.

Anti-edema effect of melatonin on spinal cord injury in rats

“…Oshio et al found that AQP4 was intensely stained throughout the gray matter in spinal cord, especially in the capillary-surrounding astrocytic end-feet 19 . In particular, AQP4 and spinal cord edema are positively correlated 40,41 . AQP4 in spinal cord is expressed in glial cells throughout the gray matter and glial foot processes adjacent to the spinal capillary endothelium 19 .…”

Myxoma virus derived immune modulating proteins, M-T7 and Serp-1, reduce early inflammation after spinal cord injury in the rat model

“…Spinal cord trauma initiates a severe and prolonged inflammatory response [21][22][23][24] with destruction of the spinal cord tissue surrounding the site of injury and causing a gradual expansion of the cavity of injury (COI) [18,35,40]. Phagocytic macrophages loaded with luxol fast blue-positive myelin granules have been observed in SCI lesions beyond 8 weeks post-injury [21] and are considered central mediators of this destructive inflammation.…”

“…Macrophages continue to phagocytize myelin, persisting for more than 8 weeks post-spinal cord injury (SCI) [21]. As this inflammatory, phagocytic macrophage infiltrate persists, the cavity of injury (COI) increases in volume [18,35,40] creating a barrier for axonal regeneration [20], while the surrounding spinal cord tissue is irreversibly destroyed. Based on these histopathological findings we have postulated that a reduction in the numbers of macrophages in the COI by pharmacological treatments has the potential to protect the nervous system, a therapy designed to limit tissue destruction and potentially reduce neurological deficits.…”

Aquaporins in the Spinal Cord

“…A study by Hemley et al [93] has shown a relation between the increase of astrocytic AQP4 expression and the persistence of syrinxes in a rat model of posttraumatic syringomyelia where a significant up-regulation of AQP4 was observed at three and six weeks post injury at the level of the syrinx and in adjacent rostral and caudal levels.…”