Objectives

The present study was undertaken to investigate the effects and related mechanisms of hypothermia on oxidative stress and apoptosis caused by cardiac arrest (CA)-induced brain damage in rats.

Methods

The CA/CPR model was initiated by asphyxia. Body temperature in the normothermia and hypothermia groups was maintained at 37°C ± 0.2°C and 34°C ± 0.2°C, respectively, by surface cooling with an ice pack. First, neurological deficit scores (NDSs) were assessed, and then hippocampus samples were collected at 24 and 72 h after return of spontaneous circulation (ROSC).

Results

The NDSs of rats were significantly reduced after CA, and hypothermia ameliorated neurological deficits. Varying degrees of changes in cellular nuclei and mitochondria were observed in the hippocampus following CA; however, morphological changes became less apparent after therapeutic hypothermia. Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were higher in the hippocampus at 24 h after ROSC. In contrast, hypothermia did not alter MDA content, while SOD activity further increased. Furthermore, hypothermia reversed the caspase-3 enhancement observed in the normothermia group at 24 h after ROSC. CA also inhibited GSK-3β phosphorylation, promoted Nrf2 translocation to the nucleus, and downregulated HO-1 expression. However, hypothermia significantly reversed these CA-induced changes in GSK-3β phosphorylation, Nrf2 translocation, and HO-1 expression.

Conclusion

Hypothermia attenuated CA-induced neurological deficits and hippocampal morphology changes in rats. The protective effect of hypothermia following CA may have been related to inhibition of oxidative stress and apoptosis, and its underlying mechanisms may have been due, at least in part, to activation of the GSK-3β/Nrf2/HO-1 pathway.

中文翻译：

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在心脏骤停引起的脑损伤的大鼠模型中，低温治疗通过GSK-3β/ Nrf2 / HO-1信号通路防止海马氧化应激和细胞凋亡。

目标

本研究旨在探讨低温对大鼠心脏骤停（CA）引起的脑损伤所引起的氧化应激和细胞凋亡的影响及其相关机制。

方法

CA / CPR模型是由窒息引发的。通过用冰袋进行表面冷却，常温和低温组的体温分别维持在37°C±0.2°C和34°C±0.2°C。首先，评估神经功能缺损评分（NDS），然后在自发循环（ROSC）恢复后的24和72 h收集海马样本。

结果

CA后大鼠的NDS显着降低，体温过低改善了神经功能缺损。CA后海马中细胞核和线粒体的变化程度不同。然而，低温治疗后形态学改变变得不那么明显。ROSC后24小时，海马中丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性较高。相反，低温不改变MDA含量，而SOD活性进一步增加。此外，低温在ROSC后24小时逆转了在常温组中观察到的caspase-3增强。CA还抑制GSK-3β磷酸化，促进Nrf2易位至细胞核，并下调HO-1表达。但是，体温过低会明显逆转这些CA诱导的GSK-3β磷酸化，Nrf2易位，

结论

体温过低可减轻CA诱导的大鼠神经功能缺损和海马形态学变化。CA后低温治疗的保护作用可能与氧化应激和细胞凋亡的抑制有关，其潜在机制可能至少部分归因于GSK-3β/ Nrf2 / HO-1途径的激活。