Toward an understanding of dural ectasia: A light microscopy study in a murine model of Marfan syndrome

Study Design. Light microscopy study of the lumbar spinal meninges of a murine model of Marfan syndrome. Objective. Characterize the pathology of the lumbosacral meninges in Marfan syndrome, seeking clues to the pathophysiology behind dural ectasia. Summary of Background Data. Dural ectasia is common in Marfan syndrome. The etiology of dural ectasia is unknown, but is conjectured to be related to constitutionally weak spinal dura. The morphology of the lumbar dura in Marfan syndrome has not been described, as it has in other tissues affected by Marfan syndrome. Methods. The lumbosacral dura were removed from three 4-month-old mice, 1 homozygote (mgR/mgR) expressing the murine Marfan phenotype, 1 heterozygote expressing wild-type phenotype, and 1 homozygote wildtype. Hematoxylin and eosin, elastochrome, and immunohistochemical stains against activated transforming growth factor β, gelatinase A (matrix metalloproteinase-2), and gelatinase-B (matrix metalloproteinase-9) were used for light microscopic evaluation. Results. No difference was noted between the heterozygous and wild-type mice in dural connective tissue morphology. The homozygote (mgR/mgR) had a marked attenuation of the dura overall, in addition to elastic fiber disorganization. The homozygote dura also stained for increased presence of activated transforming growth factor β and matrix metalloproteinase-2, but not matrix metalloproteinase-9. Conclusions. These morphologic findings in the Marfan phenotype mouse mimic the findings of disordered elasticfibers in other Marfan tissues and demonstrate gross attenuation of the tissue architecture, corroborating the theory that dural ectasia in Marfan syndrome results from hydrostatic pressure on weakened dura. These changes may be due in part to transforming growth factor β over-activation and gelatinase-A-mediated elastolysis and collagen breakdown.