Simvastatin protects ischemic spinal cord injury from cell death and cytotoxicity through decreasing oxidative stress: i
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RESEARCH ARTICLE
Open Access
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 deprivationreoxygenation conditions Hye-Min Sohn1, Jin-Young Hwang2, Jung-Hee Ryu1, Jinhee Kim1, Seongjoo Park1, Jin-woo Park1 and Sung-Hee Han1*
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. Keywords: Ischemia–reperfusion injury, Neuroprotection, Oxidative stress, Oxygen–glucose deprivation, Simvastatin, Spinal cord injury
* Correspondence: [email protected] 1 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 Full list of author information is available at the end of the article © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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