title: Histologic characterization of acute spinal cord injury treated with intravenous methylprednisolone.
abstract: OBJECTIVE
  Many substances have been investigated for attenuation of spinal cord injury after acute trauma; however, pharmacologically only steroid administration has shown clinical benefits. This study attempts to characterize local spinal cord histologic response to human dose equivalent (HDE) intravenous methylprednisolone (MP) administration in a rodent model of acute spinal cord injury.
  
  
  METHODS
  Forty-eight Sprague-Dawley rats were divided equally into control and experimental groups. Each group was subdivided into eight sets of three animals each, according to postinjury intervals. Paraplegia after lower thoracic laminectomy was achieved using a standardized weight drop technique.
  
  
  METHODS
  Within one hour, experimental animals were treated with HDE MP followed by 23-hour continuous infusion of HDE MP. Spinal cords were harvested at variable intervals postinjury and prepared for histologic/immunohistochemistry examination.
  
  
  METHODS
  Edema, necrosis, and glial fibrillary acidic protein (GFAP) positivity in the specimens from treated/control groups were graded by microscopy and immunohistochemistry staining and compared in a blinded manner by a qualified neuropathologist and senior authors.
  
  
  RESULTS
  Minimal differences were observed between control and MP-treated animals at zero and four hours. At eight hours, increased white matter and medullary edema was evident in control versus MP-treated rats. This trend continued through twelve, sixteen, twenty-four, forty-eight, and seventy-two hours. No difference was observed in the astrocytic response to injury by GFAP immunohistochemistry between the groups.
  
  
  CONCLUSIONS
  Histologically, MP reduces the development of severe edema and preserves spinal cord architecture adjacent to the site of injury. In contrast, MP does not alter the development of spinal cord necrosis or astrocytic response at the zone of injury.
authors.affiliation: Department of Orthopaedic Surgery, Health Science Center at Brooklyn, State University of New York, Brooklyn, New York 10011, USA. amerola@pol.net
authors.forename: A
authors.initials: A
authors.lastname: Merola
authors.forename: Michael F
authors.initials: MF
authors.lastname: O'Brien
authors.forename: B Andrew
authors.initials: BA
authors.lastname: Castro
authors.forename: David A B
authors.initials: DA
authors.lastname: Smith
authors.forename: James M
authors.initials: JM
authors.lastname: Eule
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Lowe
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Dwyer
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Haher
authors.forename: N J
authors.initials: NJ
authors.lastname: Espat
mesh_terms: D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001253:Astrocytes; D004195:Disease Models, Animal; D004487:Edema / Q000188:drug therapy; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007262:Infusions, Intravenous; D008775:Methylprednisolone / Q000008:administration & dosage*; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology*; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D005904:Glial Fibrillary Acidic Protein; D008775:Methylprednisolone