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

BackgroundIschemia 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 injuryMethodsPrimary 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).ResultsOGD 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).ConclusionsSimvastatin effectively reduced spinal cord neuronal death and cytotoxicity against ischemia–reperfusion injury, probably via modification of oxidative stress.

Simvastatin Protects Dopaminergic Neurons Against MPP+-Induced Oxidative Stress and Regulates the Endogenous Anti-Oxidant System Through ERK

“…The data from this study provide new insights into the neuroprotective mechanisms of Sim. Previous clinical studies revealed that Sim has the potential to decrease the risk of PD by lowering oxidative stress [12,13], and it can also affect the suppressive potential of pathological alpha-Syn by lowering cholesterol levels [14]. The fact that Sim can cross the blood-brain barrier as well as the considerable evidence supporting the beneficial effects of Sim on the central nervous system make Sim one of the more promising drugs for treating neurodegenerative diseases, including stroke [15,16] and PD [17,18].…”

Bone mesenchymal stem cell‐conditioned medium attenuates the effect of oxidative stress injury on NSCs by inhibiting the Notch1 signaling pathway

“…This finding suggests that the functional recovery after SCI is possible (Badner and Siddiqui, 2017). However, it is difficult for NSCs to survive because of the oxidative stress environment after SCI (Sohn et al, 2017). Therefore, reducing oxidative stress injury is a vital process for NSCs to treat SCI.…”

“…Neural stem cells (NSCs) are one of the main type of stem cells. However, it is difficult for NSCs to survive because of the oxidative stress environment after SCI (Sohn et al, 2017). This finding suggests that the functional recovery after SCI is possible (Badner and Siddiqui, 2017).…”

Lycium Barbarum Polysaccharides Alleviates Oxidative Damage Induced by H2O2 Through Down-Regulating MicroRNA-194 in PC-12 and SH-SY5Y Cells

“…Moreover, the neurons in the CNS contain low levels of antioxidant enzymes [6]. Therefore, the neurons in the CNS are vulnerable to oxidative damage due to the low antioxidant ability and limited scope for up-regulation when the oxidative stress is enhanced [6]. The above descriptions indicate that oxidative stress is a promising therapeutic target for SCI treatments [7].…”

“…In the cell membranes of the CNS, there are a great amount of lipids which are easily vulnerable to free radical. Moreover, the neurons in the CNS contain low levels of antioxidant enzymes [6]. Therefore, the neurons in the CNS are vulnerable to oxidative damage due to the low antioxidant ability and limited scope for up-regulation when the oxidative stress is enhanced [6].…”