Peroxiredoxin-5 alleviates early brain injury after subarachnoid hemorrhage by reducing oxidative stress

IF 3.5 3区医学 Q2 NEUROSCIENCES Brain Research Bulletin Pub Date : 2024-09-24 DOI:10.1016/j.brainresbull.2024.111087

Jinshuo Yang, Qiaowei Wu, Shuai Lan, Kaikun Yuan, Bowen Sun, Yuxiao Meng, Shancai Xu, Huaizhang Shi

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Abstract

Background and purpose

Following subarachnoid hemorrhage (SAH), excessive activation of oxidative stress and cell apoptosis plays a critical role in early brain injury (EBI). Peroxiredoxin-5 (Prdx5), predominantly expressed in neuronal mitochondria, acts as an antioxidant. However, the role of Prdx5 in EBI after SAH remains unclear. This study aims to elucidate the antioxidative stress and anti-apoptotic effects of Prdx5 in rats following SAH.

Methods

In this study, an SAH model was established in Sprague-Dawley rats using endovascular perforation. Recombinant Prdx5 (rPrdx5) was administered intranasally to upregulate Prdx5 expression after SAH in rats. Prdx5 small interfering RNA (Prdx5 siRNA) was administered prior to SAH modelling. The neuroprotective effects of Prdx5 were validated through SAH grading, brain water content, blood-brain barrier permeability, neurobehavioral tests, immunofluorescence, TUNEL staining, and Western blotting.

Results

The expression levels of endogenous Prdx5 significantly decreased after SAH. Treatment with rPrdx5 improved both short-term and long-term behaviour in rats, reduced brain water content and blood-brain barrier permeability, and exhibited anti-oxidative stress and anti-apoptotic effects. Measurements of oxidative stress-related indicators, including MDA, SOD, GSH-Px and GSH/GSSG, confirmed that Prdx5 can alleviate oxidative stress in rats after SAH. Western blot analysis showed that rPrdx5 significantly increased the expression of Bcl-XL and Bcl-2 and reduced the expression of Bax and Cleaved Caspase-3, thereby exerting anti-apoptotic effects. Additionally, Prdx5 siRNA reversed the neuroprotective effects of rPrdx5, exacerbated neuronal damage and blood-brain barrier permeability, and increased levels of oxidative stress and apoptosis.

Conclusion

In conclusion, our study demonstrated that specifically upregulating the expression of Prdx5 can reduce oxidative stress and apoptosis in rats after SAH, while also improving both short-term and long-term neurological impairments. Prdx5 is primarily expressed in the mitochondria of neuronal cells and is a crucial target for reducing ROS after SAH. rPrdx5 treatment may offer a promising therapeutic approach for clinical SAH patients.

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过氧化还原酶-5能通过减少氧化应激减轻蛛网膜下腔出血后的早期脑损伤。

背景和目的：蛛网膜下腔出血（SAH）后，氧化应激的过度激活和细胞凋亡在早期脑损伤（EBI）中起着至关重要的作用。过氧化物歧化酶-5（Prdx5）主要在神经元线粒体中表达，是一种抗氧化剂。然而，Prdx5 在 SAH 后 EBI 中的作用仍不清楚。本研究旨在阐明 Prdx5 在 SAH 后大鼠体内的抗氧化应激和抗凋亡作用：方法：本研究采用血管内穿孔法在 Sprague-Dawley 大鼠中建立 SAH 模型。腹腔注射重组 Prdx5（rPrdx5）以上调 SAH 后大鼠的 Prdx5 表达。在 SAH 建模前给大鼠注射 Prdx5 小干扰 RNA（Prdx5 siRNA）。通过SAH分级、脑含水量、血脑屏障通透性、神经行为测试、免疫荧光、TUNEL染色和Western印迹等方法验证了Prdx5的神经保护作用：结果：SAH后内源性Prdx5的表达水平明显下降。用rPrdx5治疗可改善大鼠的短期和长期行为，降低脑水含量和血脑屏障通透性，并具有抗氧化应激和抗细胞凋亡作用。对氧化应激相关指标（包括MDA、GSH-Px、SOD和GSH/GSSG）的测定证实，Prdx5能缓解SAH后大鼠的氧化应激。Western印迹分析表明，rPrdx5能显著增加Bcl-XL和Bcl-2的表达，降低Bax和Caspase-3的表达，从而发挥抗凋亡作用。此外，Prdx5 siRNA逆转了rPrdx5的神经保护作用，加剧了神经元损伤和血脑屏障通透性，增加了氧化应激和细胞凋亡水平：总之，我们的研究表明，特异性上调Prdx5的表达可减少SAH后大鼠的氧化应激和细胞凋亡，同时还能改善短期和长期的神经功能损伤。Prdx5 主要在神经细胞的线粒体中表达，是减少 SAH 后 ROS 的关键靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain Research Bulletin 医学-神经科学

CiteScore

6.90

自引率

2.60%

发文量

253

审稿时长

67 days

期刊介绍： The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.