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An in vivo model of anti-inflammatory activity of subdural dexamethasone following the spinal cord injury
Affiliations- Department of Pathology and Molecular Medicine, M. deGroote School of Medicine, McMaster University, Hamilton, Canada
- Department of Neurosurgery and Paediatric Neurosurgery, Medical University of Lublin, Lublin, Poland
- Sunnybrook Health Sciences Centre, Department of Medical Biophysics, University of Toronto, Toronto, Canada
- Department of Orthopaedic and Traumatology, Medical University of Lublin, Lublin, Poland
- Department of Anaesthesiology and Intensive Therapy, Medical University of Lublin, Lublin, Poland
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Abstract
Current therapies to limit the neural tissue destruction following the spinal cord injury are not effective. Our recent studies indicate that the injury to the white matter of the spinal cord results in a severe inflammatory response where macrophages phagocytize damaged myelin and the fluid-filled cavity of injury extends in size with concurrent and irreversible destruction of the surrounding neural tissue over several months. We previously established that a high dose of 4mg/rat of dexamethasone administered for 1 week via subdural infusion remarkably lowers the numbers of infiltrating macrophages leaving large amounts of un-phagocytized myelin debris and therefore inhibits the severity of inflammation and related tissue destruction. But this dose was potently toxic to the rats. In the present study the lower doses of dexamethasone, 0.125–2.0mg, were administered via the subdural infusion for 2 weeks after an epidural balloon crush of the mid-thoracic spinal cord. The spinal cord cross-sections were analyzed histologically. Levels of dexamethasone used in the current study had no systemic toxic effect and limited phagocytosis of myelin debris by macrophages in the lesion cavity. The subdural infusion with 0.125–2.0mg dexamethasone over 2 week period did not eliminate the inflammatory process indicating the need for a longer period of infusion to do so. However, this treatment has probably lead to inhibition of the tissue destruction by the severe, prolonged inflammatory process.
Abstract
Current therapies to limit the neural tissue destruction following the spinal cord injury are not effective. Our recent studies indicate that the injury to the white matter of the spinal cord results in a severe inflammatory response where macrophages phagocytize damaged myelin and the fluid-filled cavity of injury extends in size with concurrent and irreversible destruction of the surrounding neural tissue over several months. We previously established that a high dose of 4mg/rat of dexamethasone administered for 1 week via subdural infusion remarkably lowers the numbers of infiltrating macrophages leaving large amounts of un-phagocytized myelin debris and therefore inhibits the severity of inflammation and related tissue destruction. But this dose was potently toxic to the rats. In the present study the lower doses of dexamethasone, 0.125–2.0mg, were administered via the subdural infusion for 2 weeks after an epidural balloon crush of the mid-thoracic spinal cord. The spinal cord cross-sections were analyzed histologically. Levels of dexamethasone used in the current study had no systemic toxic effect and limited phagocytosis of myelin debris by macrophages in the lesion cavity. The subdural infusion with 0.125–2.0mg dexamethasone over 2 week period did not eliminate the inflammatory process indicating the need for a longer period of infusion to do so. However, this treatment has probably lead to inhibition of the tissue destruction by the severe, prolonged inflammatory process.
Keywords
Spinal cord injury, Phagocytosis of myelin debris, Cavity of CNS injury, Subdural infusion, Inhibition of secondary inflammation
About this articleTitle
An in vivo model of anti-inflammatory activity of subdural dexamethasone following the spinal cord injury
Journal
Neurologia i Neurochirurgia Polska
Issue
Pages
7-15
Page views
386
Article views/downloads
435
DOI
10.1016/j.pjnns.2015.10.006
Bibliographic record
Neurol Neurochir Pol 2016;50(1):7-15.
Keywords
Spinal cord injury
Phagocytosis of myelin debris
Cavity of CNS injury
Subdural infusion
Inhibition of secondary inflammation
Authors
Jacek M. Kwiecien
Bozena Jarosz
Wendy Oakden
Michal Klapec
Greg J. Stanisz
Kathleen H. Delaney
Edyta Kotlinska-Hasiec
Rafal Janik
Radoslaw Rola
Wojciech Dabrowski
