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Experimental studies into the pathophysiology of syringomyelia
thesisposted on 2022-03-28, 20:29 authored by Sarah J. Hemley
Syringomyelia, a condition in which an enlarging cyst forms within the spinal cord, can result in motor weakness and pain. The pathogenesis of syringomyelia is poorly understood and treatment outcomes are not always satisfactory. It is unlikely that more effective therapies will be developed without a greater understanding of the mechanisms underlying spinal cord cyst formation. It is generally thought that syringomyelia is simply caused by an increase in the flow of cerebrospinal fluid (CSF) into the spinal cord. However, the pathogenesis is likely to be complex and multifactorial. It was proposed that: 1) a possible contribution to fluid flow is from vessels adjacent to the cyst, through a deficiency in the blood-spinal cord barrier (BSCB); 2) an increase in the expression of the water channel protein aquaporin-4 (AQP4) could increase the movement of water into the cyst; and 3) fluid outflow contributes to the pathology. Well established animal models of posttraumatic and Chiari-associated syringomyelia were used to study BSCB integrity, AQP4 expression and fluid outflow pathways. Integrity of the BSCB was assessed using immunoreactivity to endothelial barrier antigen and by extravasation of intravascular horseradish peroxidase (HRP). Western blotting and immunofluorescence was used to examine AQP4 and glial fibrillary acidic protein (GFAP) expression. Outflow of fluid was investigated by the direct microinjection of tracer into cysts under ultrasound guidance. These studies demonstrated a prolonged disruption of the BSCB directly surrounding the cyst. This disruption may be allowing a greater volume of fluid to pass from the blood stream into the spinal cord, causing the cyst to enlarge. There was a change in the levels of AQP4, suggesting that there is an imbalance in the water movement in the spinal cord. This imbalance may be contributing to fluid accumulation in syringomyelia. The study of fluid outflow found that fluid diffuses out of cysts into the surrounding extracellular space and perivascular spaces. This is the first study to demonstrate a route for fluid flow out of the cyst and will add to our understanding of fluid movement in syringomyelia.