Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our results indicated a significant increase in the level of acrolein after ICH in mouse brain. In primary neurons, acrolein induced an increase in mitochondrial fragmentation, loss of mitochondrial membrane potential, generation of reactive oxidative species, and release of mitochondrial cytochrome c. Mechanistically, acrolein facilitated the translocation of dynamin-related protein1 (Drp1) from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission. Further studies found that treatment with hydralazine (an acrolein scavenger) significantly reversed Drp1 translocation and the morphological damage of mitochondria after ICH. In parallel, the neural apoptosis, brain edema, and neurological functional deficits induced by ICH were also remarkably alleviated. In conclusion, our results identify acrolein as an important contributor to the secondary brain injury following ICH. Meanwhile, we uncovered a novel mechanism by which Drp1-mediated mitochondrial oxidative damage is involved in acrolein-induced brain injury.

中文翻译：

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丙烯醛加重了Drp1介导的线粒体氧化损伤对小鼠的脑出血后的继发性脑损伤。

颅内出血（ICH）的临床研究进展受到对导致继发性脑损伤的分子机制的不完全了解所限制。丙烯醛是一种高度活性的不饱和醛，已与许多神经系统疾病有关。我们的结果表明，老鼠脑内ICH后丙烯醛水平显着增加。在原代神经元中，丙烯醛诱导线粒体片段化增加，线粒体膜电位丧失，反应性氧化物质的产生以及线粒体细胞色素c的释放。从机理上讲，丙烯醛促进了动力蛋白相关蛋白1（Drp1）从细胞质到线粒体膜的转运，并导致线粒体过度裂变。进一步的研究发现，肼苯哒嗪（一种丙烯醛清除剂）治疗可显着逆转ICH后Drp1易位和线粒体的形态损害。同时，由ICH引起的神经细胞凋亡，脑水肿和神经功能缺损也得到明显缓解。总之，我们的研究结果表明丙烯醛是ICH后继发性脑损伤的重要因素。同时，我们发现了Drp1介导的线粒体氧化损伤参与丙烯醛诱导的脑损伤的一种新机制。我们的研究结果表明丙烯醛是ICH后继发性脑损伤的重要因素。同时，我们发现了Drp1介导的线粒体氧化损伤参与丙烯醛诱导的脑损伤的一种新机制。我们的研究结果表明丙烯醛是ICH后继发性脑损伤的重要因素。同时，我们发现了Drp1介导的线粒体氧化损伤参与丙烯醛诱导的脑损伤的一种新机制。