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首页> 外文期刊>Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism >Reduction in oxidative stress by superoxide dismutase overexpression attenuates acute brain injury after subarachnoid hemorrhage via activation of Akt/glycogen synthase kinase-3beta survival signaling.
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Reduction in oxidative stress by superoxide dismutase overexpression attenuates acute brain injury after subarachnoid hemorrhage via activation of Akt/glycogen synthase kinase-3beta survival signaling.

机译:超氧化物歧化酶过表达减少氧化应激通过激活Akt /糖原合酶激酶3β生存信号转导减轻蛛网膜下腔出血后的急性脑损伤。

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摘要

Recent studies have revealed that oxidative stress has detrimental effects in several models of neurodegenerative diseases, including subarachnoid hemorrhage (SAH). However, how oxidative stress affects acute brain injury after SAH remains unknown. We have previously reported that overexpression of copper/zinc-superoxide dismutase (SOD1) reduces oxidative stress and subsequent neuronal injury after cerebral ischemia. In this study, we investigated the relationship between oxidative stress and acute brain injury after SAH using SOD1 transgenic (Tg) rats. SAH was produced by endovascular perforation in wild-type (Wt) and SOD1 Tg rats. Apoptotic cell death at 24 h, detected by a cell death assay, was significantly decreased in the cerebral cortex of the SOD1 Tg rats compared with the Wt rats. The mortality rate at 24 h was also significantly decreased in the SOD1 Tg rats. A hydroethidine study demonstrated that superoxide anion production after SAH was reduced in the cerebral cortex of the SOD1 Tg rats. Moreover, phosphorylation of Akt and glycogen synthase kinase-3beta (GSK3beta), which are survival signals in apoptotic cell death, was more enhanced in the cerebral cortex of the SOD1 Tg rats after SAH using Western blot analysis and immunohistochemistry. We conclude that reduction in oxidative stress by SOD1 overexpression may attenuate acute brain injury after SAH via activation of Akt/GSK3beta survival signaling.
机译:最近的研究表明,氧化应激在多种神经退行性疾病模型(包括蛛网膜下腔出血(SAH))中具有有害作用。然而,尚不清楚SAH后氧化应激如何影响急性脑损伤。先前我们已经报道过铜/锌超氧化物歧化酶(SOD1)的过表达减少了脑缺血后的氧化应激和随后的神经元损伤。在这项研究中,我们调查了SOD1转基因(Tg)大鼠SAH后氧化应激与急性脑损伤之间的关系。 SAH是在野生型(Wt)和SOD1 Tg大鼠中通过血管内穿孔产生的。与Wt大鼠相比,SOD1 Tg大鼠大脑皮层通过细胞死亡试验检测到的24 h凋亡细胞死亡明显减少。 SOD1 Tg大鼠24 h的死亡率也显着降低。氢乙啶研究表明,SOD1 Tg大鼠的大脑皮层中SAH后超氧阴离子的产生减少。此外,Akt和糖原合酶激酶3β(GSK3beta),是凋亡细胞死亡的生存信号,在SAH后使用Western blot分析和免疫组化在SOD1 Tg大鼠的大脑皮层中的磷酸化得到了进一步增强。我们得出的结论是,通过激活Akt / GSK3beta生存信号,SOD1过表达可以减轻氧化应激,从而减轻SAH后的急性脑损伤。

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