Protective effects of cyclosporine A and hypothermia on neuronal mitochondria in a rat asphyxial cardiac arrest model

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• 作者：Jie Liu ; MD ; Yue Wang ; MD ; Qiwei Zhuang ; MD ; Meng Chen ; MD ; Yufeng Wang ; MD ; Lina Hou ; MD ; Fei Han ; MD ; PhD ; ^{fh.feih@yahoo.com" class="auth_mail" title="E-mail the corresponding author}
• 刊名：The American Journal of Emergency Medicine
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：34
• 期：6
• 页码：1080-1085
• 全文大小：663 K

文摘

Cyclosporine A (CsA) was neuroprotective in the settings of traumatic brain injury and stroke. We sought to investigate the protective effects of CsA and hypothermia on neuronal mitochondria after cardiac arrest.

Methods and Results

Five groups were included: sham (S), normothermia (N), CsA (C), hypothermia (H), and CsA plus hypothermia (C + H). Cardiac arrest was induced by 10 min of asphyxia. CsA (10 mg/kg) was administered immediately after return of spontaneous circulation in the CsA groups. Temperature of the rats was maintained at 33 ± 0.5 °C after return of spontaneous circulation in the hypothermia groups. Hippocampal mitochondria were measured after 2 h of resuscitation. Mitochondrial transmembrane potential was significantly higher in the C, the H, and the C + H groups than in the N group and was higher in the C + H group than in the C and the H groups. Cytosolic cytochrome c was significantly higher in the N group. Superoxide dismutase activity was significantly lower in the N group than in the other groups and was higher in the C and the C + H groups than in the H group. Malondialdehyde concentration was significantly higher in the N group.

Conclusions

CsA or hypothermia used immediately after resuscitation enhanced mitochondrial transmembrane potential, kept cytochrome c from releasing out of the mitochondria, increased superoxide dismutase activity, and decreased malondialdehyde concentration in hippocampus. Moreover, the protective effects of CsA were reinforced by hypothermia. One of the mechanisms that hypothermia protected neuronal mitochondria from damage was inhibiting the opening of mitochondrial permeability transition pore.