title: Simvastatin protects ischemic spinal cord injury from cell death and cytotoxicity through decreasing oxidative stress: in vitro primary cultured rat spinal cord model under oxygen and glucose deprivation-reoxygenation conditions.
abstract: BACKGROUND
  Ischemia and the following reperfusion damage are critical mechanisms of spinal cord injury. Statins have been reported to decrease ischemia-reperfusion injury in many organs including the spinal cord. Anti-oxidative effect is one of the main protective mechanisms of statin against neuronal death and cytotoxicity. We hypothesized that statins' anti-oxidative property would yield neuroprotective effects on spinal cord ischemia-reperfusion injury METHODS: Primary cultured spinal cord motor neurons were isolated from Sprague-Dawley rat fetuses. Ischemia-reperfusion injury model was induced by 60 min of oxygen and glucose deprivation (OGD) and 24 h of reoxygenation. Healthy and OGD cells were treated with simvastatin at concentrations of 0.1, 1, and 10 μM for 24 h. Cell viability was assessed using water-soluble tetrazolium salt (WST)-8, cytotoxicity with LDH, and production of free radicals with DCFDA (2',7'-dichlorofluorescein diacetate).
  
  
  RESULTS
  OGD reduced neuronal viability compared to normoxic control by 35.3%; however, 0.1-10 μM of simvastatin treatment following OGD improved cell survival. OGD increased LDH release up to 214%; however, simvastatin treatment attenuated its cytotoxicity at concentrations of 0.1-10 μM (p < 0.001 and p = 0.001). Simvastatin also reduced deteriorated morphological changes of motor neurons following OGD. Oxidative stress was reduced by simvastatin (0.1-10 μM) compared to untreated cells exposed to OGD (p < 0.001).
  
  
  CONCLUSIONS
  Simvastatin effectively reduced spinal cord neuronal death and cytotoxicity against ischemia-reperfusion injury, probably via modification of oxidative stress.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.
authors.forename: Hye-Min
authors.initials: HM
authors.lastname: Sohn
authors.affiliation: Department of Anesthesiology and Pain Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea.
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Hwang
authors.affiliation: Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Ryu
authors.affiliation: Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.
authors.forename: Jinhee
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.
authors.forename: Seongjoo
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea. 21ambi@hanmail.net.
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Han
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005947:Glucose / Q000172:deficiency; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D009046:Motor Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology*
chemical_list: D003470:Culture Media; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018696:Neuroprotective Agents; D019821:Simvastatin; D005947:Glucose
keywords: Ischemia–reperfusion injury; Neuroprotection; Oxidative stress; Oxygen–glucose deprivation; Simvastatin; Spinal cord injury