Joel Berliner1, Sarah Hemley2, Elmira Najafi2, Lynne Bilston3,4, Marcus Stoodley2, Magdalena Lam2. 1. Faculty of Medicine and Health Sciences, 2 Technology Place, Macquarie University, Sydney, NSW, 2109, Australia. joel.berliner@hdr.mq.edu.au. 2. Faculty of Medicine and Health Sciences, 2 Technology Place, Macquarie University, Sydney, NSW, 2109, Australia. 3. Neuroscience Research Australia, Margarete Ainsworth Building, 139 Barker Street, Randwick, NSW, 2031, Australia. 4. Prince of Wales Clinical School, Faculty of Medicine, University of New South Wales, Randwick, NSW, 2031, Australia.
Abstract
BACKGROUND: Syringomyelia is a serious complication of spinal cord trauma, occurring in approximately 28% of spinal cord injuries. Treatment options are limited and often produce unsatisfactory results. Post-traumatic syringomyelia (PTS) is presumably related to abnormalities of cerebrospinal fluid (CSF) and interstitial fluid hydrodynamics, but the exact mechanisms are unknown. METHODS: Transmission electron microscopy (TEM) was used to investigate in detail the interfaces between fluid and tissue in the spinal cords of healthy Sprague-Dawley rats (n = 3) and in a rat model of PTS (n = 3). PTS was induced by computer-controlled impact (75 kDyn) to the spinal cord between C6 and C8, followed by a subarachnoid injection of kaolin to produce focal arachnoiditis. Control animals received a laminectomy only to C6 and C7 vertebrae. Animals were sacrificed 12 weeks post-surgery, and spinal cords were prepared for TEM. Ultra-thin spinal cord sections at the level of the injury were counterstained for structural anatomy. RESULTS: Spinal cords from animals with PTS displayed several abnormalities including enlarged perivascular spaces, extracellular edema, cell death and loss of tissue integrity. Additionally, alterations to endothelial tight junctions and an abundance of pinocytotic vesicles, in tissue adjacent to syrinx, suggested perturbations to blood-spinal cord barrier (BSCB) function. CONCLUSIONS: These findings support the hypothesis that perivascular spaces are important pathways for CSF flow into and out of the spinal cord, but also suggest that fluid may enter the cord through vesicular transport and an altered BSCB.
BACKGROUND:Syringomyelia is a serious complication of spinal cord trauma, occurring in approximately 28% of spinal cord injuries. Treatment options are limited and often produce unsatisfactory results. Post-traumatic syringomyelia (PTS) is presumably related to abnormalities of cerebrospinal fluid (CSF) and interstitial fluid hydrodynamics, but the exact mechanisms are unknown. METHODS: Transmission electron microscopy (TEM) was used to investigate in detail the interfaces between fluid and tissue in the spinal cords of healthy Sprague-Dawley rats (n = 3) and in a rat model of PTS (n = 3). PTS was induced by computer-controlled impact (75 kDyn) to the spinal cord between C6 and C8, followed by a subarachnoid injection of kaolin to produce focal arachnoiditis. Control animals received a laminectomy only to C6 and C7 vertebrae. Animals were sacrificed 12 weeks post-surgery, and spinal cords were prepared for TEM. Ultra-thin spinal cord sections at the level of the injury were counterstained for structural anatomy. RESULTS: Spinal cords from animals with PTS displayed several abnormalities including enlarged perivascular spaces, extracellular edema, cell death and loss of tissue integrity. Additionally, alterations to endothelial tight junctions and an abundance of pinocytotic vesicles, in tissue adjacent to syrinx, suggested perturbations to blood-spinal cord barrier (BSCB) function. CONCLUSIONS: These findings support the hypothesis that perivascular spaces are important pathways for CSF flow into and out of the spinal cord, but also suggest that fluid may enter the cord through vesicular transport and an altered BSCB.
Authors: Ravi Teja Kedarasetti; Kevin L Turner; Christina Echagarruga; Bruce J Gluckman; Patrick J Drew; Francesco Costanzo Journal: Fluids Barriers CNS Date: 2020-08-20