Toshitaka Seki1, Michael G Fehlings. 1. Division of Cell and Molecular Biology, Toronto Western Research Institute, Krembil Neuroscience Center, University Health Network, University of Toronto, Ontario, Canada.
Abstract
OBJECT: Although posttraumatic syringomyelia (PTS) develops in up to 30% of patients after spinal cord injury (SCI), the pathophysiology of this debilitating complication is incompletely understood. To provide greater insight into the mechanisms of this degenerative sequela of SCI, the authors developed and characterized a novel model of PTS. METHODS: The spinal cords of 64 female Wistar rats were injured by 35-g modified aneurysm clip compression at the level of T6-7. Kaolin (5 microl of 500 mg/ml solution) was then injected into the subarachnoid space rostral to the site of the injury to induce inflammatory arachnoiditis in 22 rats. Control groups received SCI alone (in 21 rats), kaolin injection alone (in 15 rats), or laminectomy and durotomy alone without injury (sham surgery in 6 rats). RESULTS: The combination of SCI and subarachnoid kaolin injection resulted in a significantly greater syrinx formation and perilesional myelomalacia than SCI alone; SCI and kaolin injection significantly attenuated locomotor recovery and exacerbated neuropathic pain (mechanical allodynia) compared with SCI alone. We observed that combined SCI and kaolin injection significantly increased the number of terminal deoxytransferase-mediated deoxyuridine triphosphate nick-end labeled-positive cells at 7 days after injury (p<0.05 compared with SCI alone) and resulted in a significantly greater extent of astrogliosis and macrophage/microglial-associated inflammation at the lesion (p<0.05). CONCLUSIONS: The combination of compressive/contusive SCI with induced arachnoiditis results in severe PTS and perilesional myelomalacia, which is associated with enhanced inflammation, astrogliosis, and apoptotic cell death. The development of delayed neurobehavioral deficits and neuropathic pain in this model accurately reflects the key pathological and clinical conditions of PTS in humans.
OBJECT: Although posttraumatic syringomyelia (PTS) develops in up to 30% of patients after spinal cord injury (SCI), the pathophysiology of this debilitating complication is incompletely understood. To provide greater insight into the mechanisms of this degenerative sequela of SCI, the authors developed and characterized a novel model of PTS. METHODS: The spinal cords of 64 female Wistar rats were injured by 35-g modified aneurysm clip compression at the level of T6-7. Kaolin (5 microl of 500 mg/ml solution) was then injected into the subarachnoid space rostral to the site of the injury to induce inflammatory arachnoiditis in 22 rats. Control groups received SCI alone (in 21 rats), kaolin injection alone (in 15 rats), or laminectomy and durotomy alone without injury (sham surgery in 6 rats). RESULTS: The combination of SCI and subarachnoid kaolin injection resulted in a significantly greater syrinx formation and perilesional myelomalacia than SCI alone; SCI and kaolin injection significantly attenuated locomotor recovery and exacerbated neuropathic pain (mechanical allodynia) compared with SCI alone. We observed that combined SCI and kaolin injection significantly increased the number of terminal deoxytransferase-mediated deoxyuridine triphosphate nick-end labeled-positive cells at 7 days after injury (p<0.05 compared with SCI alone) and resulted in a significantly greater extent of astrogliosis and macrophage/microglial-associated inflammation at the lesion (p<0.05). CONCLUSIONS: The combination of compressive/contusive SCI with induced arachnoiditis results in severe PTS and perilesional myelomalacia, which is associated with enhanced inflammation, astrogliosis, and apoptotic cell death. The development of delayed neurobehavioral deficits and neuropathic pain in this model accurately reflects the key pathological and clinical conditions of PTS in humans.
Authors: O Nesic; J D Guest; D Zivadinovic; P A Narayana; J J Herrera; R J Grill; V U L Mokkapati; B B Gelman; J Lee Journal: Neuroscience Date: 2010-01-28 Impact factor: 3.590
Authors: Jacek M Kwiecien; Wojciech Dabrowski; Beata Dąbrowska-Bouta; Grzegorz Sulkowski; Wendy Oakden; Christian J Kwiecien-Delaney; Jordan R Yaron; Liqiang Zhang; Lauren Schutz; Barbara Marzec-Kotarska; Greg J Stanisz; John P Karis; Lidia Struzynska; Alexandra R Lucas Journal: PLoS One Date: 2020-03-19 Impact factor: 3.240