Evaluation of the Filum Terminale in Hereditary Equine Regional Dermal Asthenia.

The objectives of this study were to describe the anatomy, histology, and ultrastructure of the equine filum terminale (FT) and to describe the FT in hereditary equine regional dermal asthenia (HERDA), a model of human Ehlers-Danlos syndromes (EDS). Those humans suffer from tethered cord syndrome (TCS) caused by an abnormally structured FT wherein its attachment at the base of the vertebral column leads to long-term stretch-induced injury to the spinal cord. The pathophysiology of TCS in EDS is poorly understood, and there is a need for an animal model of the condition. Histopathologic and ultrastructural examinations were performed on FT from HERDA (n = 4) and control horses (n = 5) and were compared to FT from human TCS patients with and without EDS. Adipose, fibrous tissue, and neuronal elements were assessed. CD3 and CD20 immunohistochemistry was performed to clarify cell types (HERDA n = 2; control n = 5). Collagen fibrils were assessed in cross-section for fibril diameter and shape, and in longitudinal section for fibril disorganization, swelling, and fragmentation. The equine and human FT were similar, with both containing fibrous tissue, ependyma, neuropil, and nerve twigs. Hypervascularity was observed in both HERDA horses and human EDS-TCS patients and was not observed in equine or human controls. Moderate to severe abnormalities in collagen fibril orientation and architecture were observed in all HERDA horses and were similar to those observed in human EDS-TCS patients.

Avocado/Soybean Unsaponifiables, Glucosamine and Chondroitin Sulfate Combination Inhibits Proinflammatory COX-2 Expression and Prostaglandin E2 Production in Tendon-Derived Cells.

Tendinopathy, a common disorder in man and horses, is characterized by pain, dysfunction, and tendon degeneration. Inflammation plays a key role in the pathogenesis of tendinopathy. Tendon cells produce proinflammatory molecules that induce pain and tissue deterioration. Currently used nonsteroidal anti-inflammatory drugs are palliative but have been associated with adverse side effects prompting the search for safe, alternative compounds. This study determined whether tendon-derived cells' expression of proinflammatory cyclooxygenase (COX)-2 and production of prostaglandin E2 (PGE2) could be attenuated by the combination of avocado/soybean unsaponifiables (ASU), glucosamine (GLU), and chondroitin sulfate (CS). ASU, GLU, and CS have been used in the management of osteoarthritis-associated joint inflammation. Tenocytes in monolayer and microcarrier spinner cultures were incubated with media alone, or with the combination of ASU (8.3 µg/mL), GLU (11 µg/mL), and CS (20 µg/mL). Cultures were next incubated with media alone, or stimulated with interleukin-1ß (IL-1ß; 10 ng/mL) for 1 h to measure COX-2 gene expression, or for 24 h to measure PGE2 production, respectively. Tenocyte phenotype was analyzed by phase-contrast microscopy, immunocytochemistry, and Western blotting. Tendon-derived cells proliferated and produced extracellular matrix component type I collagen in monolayer and microcarrier spinner cultures. IL-1ß-induced COX-2 gene expression and PGE2 production were significantly reduced by the combination of (ASU+GLU+CS). The suppression of IL-1ß-induced inflammatory response suggests that (ASU+GLU+CS) may help attenuate deleterious inflammation in tendons.

Evaluation of the Structure of Myodural Bridges in an Equine Model of Ehlers-Danlos Syndromes.

Myodural bridges have been described in various species as connective tissue structures "bridging" small cranio-cervical muscles to the dura. Myodural bridges are thought to stabilize the dural sac during head and neck movements and promote cerebrospinal fluid motion; however, their role in neurological diseases has not yet been established. We report ultrasonographic visualization, necropsy, histopathologic and ultrastructural findings of myodural bridges in horses with hereditary equine regional dermal asthenia (HERDA), an equine model of Ehlers-Danlos syndromes. Five HERDA and 5 control horses were studied. Post-mortem examination and ultrasonographic studies (3 HERDA and 4 controls) demonstrated that the atlanto-occipital and atlanto-axial myodural bridges are dynamic structures "moving" the dura. En block resection of the myodural bridges (4 HERDA and 5 controls) was accomplished and histopathology showed myofiber degeneration in 3 HERDA horses and 1 control. Ultrastructural examination revealed loosely packed collagen fibrils with abnormal orientation in all HERDA horses compared to mild abnormalities in 2 controls. Our study provides necropsy and ultrasonographic evidence of the dynamic aspect of the myodural bridges as dural sac stabilizers. Myodural bridges may be pathologically altered in connective tissue disease as evidenced by the ultrastructural morphology in the HERDA myodural bridge.