title: The Effects of Difumarate Salt S-15176 after Spinal Cord Injury in Rats.
abstract: OBJECTIVE
  In the present study we analyzed neuroprotective and antiapoptotic effect of the difumarate salt S-15176, as an anti-ischemic, an antioxidant and a stabilizer of mitochondrial membrane in secondary damage following spinal cord injury (SCI) in a rat model.
  
  
  METHODS
  Three groups were performed with 30 Wistar rats; control (1), trauma (2), and a trauma+S-15176 (10 mg/kg i.p., dimethyl sulfoxide) treatment (3). SCI was performed at the thoracic level using the weight-drop technique. Spinal cord tissues were collected following intracardiac perfusion in 3rd and 7th days of posttrauma. Hematoxylin and eosin staining for histopatology, terminal deoxynucleotidyl transferase dUTP nick end labeling assay for apoptotic cells and immunohistochemistry for proapoptotic cytochrome-c, Bax and caspase 9 were performed to all groups. Functional recovery test were applied to each group in 3rd and 7th days following SCI.
  
  
  RESULTS
  In trauma group, edematous regions, diffuse hemorrhage, necrosis, leukocyte infiltration and severe degeneration in motor neurons were observed prominently in gray matter. The number of apoptotic cells was significantly higher (p<0.05) than control group. In the S-15176-treated groups, apoptotic cell number in 3rd and 7th days (p<0.001), also cytochrome-c (p<0.001), Bax (p<0.001) and caspase 9 immunoreactive cells (p<0.001) were significantly decreased in number compared to trauma groups. Hemorrhage and edema in the focal areas were also noticed in gray matter of treatment groups. Results of the locomotor test were significantly increased in treatment group (p<0.05) when compared to trauma groups.
  
  
  CONCLUSIONS
  We suggest that difumarate salt S-15176 prevents mitochondrial pathways of apoptosis and protects spinal cord from secondary injury and helps to preserve motor function following SCI in rats.
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, Maltepe University, Istanbul, Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Erdoğan
authors.affiliation: Medical Biology Department, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Matem
authors.initials: M
authors.lastname: Tunçdemir
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, Maltepe University, Istanbul, Turkey.
authors.forename: Bilal
authors.initials: B
authors.lastname: Kelten
authors.affiliation: Department of Neurosurgery Taksim Education and Research Hospital, Istanbul, Turkey.
authors.forename: Osman
authors.initials: O
authors.lastname: Akdemir
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, Maltepe University, Istanbul, Turkey.
authors.forename: Alper
authors.initials: A
authors.lastname: Karaoğlan
authors.affiliation: Istanbul ME-DI ENT Surgery Center, Istanbul, Turkey.
authors.forename: Erol
authors.initials: E
authors.lastname: Taşdemiroğlu
keywords: Apoptosis; Caspase-9; Cytochrome-c; Difumarate salt (S-15176); Spinal cord Injury