title: An in vivo model of anti-inflammatory activity of subdural dexamethasone following the spinal cord injury.
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.
authors: 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. Electronic address: kwiecien@mcmaster.ca.
authors: Jacek M
authors: JM
authors: Kwiecien
authors: Department of Neurosurgery and Paediatric Neurosurgery, Medical University of Lublin, Lublin, Poland. Electronic address: bozenajarosz@poczta.onet.pl.
authors: Bozena
authors: B
authors: Jarosz
authors: Sunnybrook Health Sciences Centre, Department of Medical Biophysics, University of Toronto, Toronto, Canada. Electronic address: wendy.oakden@gmail.com.
authors: Wendy
authors: W
authors: Oakden
authors: Department of Orthopaedic and Traumatology, Medical University of Lublin, Lublin, Poland. Electronic address: michalklapec@op.pl.
authors: Michal
authors: M
authors: Klapec
authors: 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. Electronic address: stanisz@sri.utoronto.ca.
authors: Greg J
authors: GJ
authors: Stanisz
authors: Department of Pathology and Molecular Medicine, M. deGroote School of Medicine, McMaster University, Hamilton, Canada.
authors: Kathleen H
authors: KH
authors: Delaney
authors: Department of Anaesthesiology and Intensive Therapy, Medical University of Lublin, Lublin, Poland. Electronic address: kedith@poczta.onet.pl.
authors: Edyta
authors: E
authors: Kotlinska-Hasiec
authors: Sunnybrook Health Sciences Centre, Department of Medical Biophysics, University of Toronto, Toronto, Canada. Electronic address: raf.janik@gmail.com.
authors: Rafal
authors: R
authors: Janik
authors: Department of Neurosurgery and Paediatric Neurosurgery, Medical University of Lublin, Lublin, Poland. Electronic address: rola.radoslaw@gmail.com.
authors: Radoslaw
authors: R
authors: Rola
authors: Department of Anaesthesiology and Intensive Therapy, Medical University of Lublin, Lublin, Poland. Electronic address: w.dabrowski5@yahoo.com.
authors: Wojciech
authors: W
authors: Dabrowski
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D060186:Infusions, Spinal; D008297:Male; D009187:Myelitis / Q000188:drug therapy* / Q000517:prevention & control; D010587:Phagocytosis / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D013355:Subdural Space
chemical_list: D000893:Anti-Inflammatory Agents; D003907:Dexamethasone
keywords: Cavity of CNS injury; Inhibition of secondary inflammation; Phagocytosis of myelin debris; Spinal cord injury; Subdural infusion