Ischemic stroke is categorized by either permanent or transient blood flow obstruction, impeding the distribution of oxygen and essential nutrients to the brain. In this study, we examined the neuroprotective effects of compound A3, a synthetic polyphenolic drug product, against ischemic brain injury by employing an animal model of permanent middle cerebral artery occlusion (p-MCAO). Ischemic stroke induced significant elevation in the levels of reactive oxygen species and, ultimately, provoked inflammatory cascade. Here, we demonstrated that A3 upregulated the endogenous antioxidant enzymes, such as glutathione s-transferase (GST), glutathione (GSH), and reversed the ischemic-stroke-induced nitric oxide (NO) and lipid peroxidation (LPO) elevation in the peri-infarct cortical and striatal tissue, through the activation of endogenous antioxidant nuclear factor E2-related factor or nuclear factor erythroid 2 (Nrf2). In addition, A3 attenuated neuroinflammatory markers such as ionized calcium-binding adapter molecule-1 (Iba-1), cyclooxygenase-2 (COX-2), tumor necrotic factor-α (TNF-α), toll-like receptors (TLR4), and nuclear factor-κB (NF-κB) by down-regulating p-JNK as evidenced by immunohistochemical results. Moreover, treatment with A3 reduced the infarction area and neurobehavioral deficits. We employed ATRA to antagonize Nrf2, which abrogated the neuroprotective effects of A3 to further assess the possible involvement of the Nrf2 pathway, as demonstrated by increased infarction and hyperexpression of inflammatory markers. Together, our findings suggested that A3 could activate Nrf2, which in turn regulates the downstream antioxidants, eventually mitigating MCAO-induced neuroinflammation and neurodegeneration.

中文翻译：

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合成多酚1,3,4恶二唑化合物A3的后处理可减轻缺血性中风引起的神经炎症和神经变性。

缺血性中风分为永久性或暂时性血流阻塞，阻碍了氧气和必需营养素向大脑的分布。在这项研究中，我们通过使用永久性大脑中动脉闭塞（p-MCAO）动物模型，研究了化合物A3（一种合成的多酚药物产品）对缺血性脑损伤的神经保护作用。缺血性中风引起活性氧水平显着升高，并最终引起炎症级联反应。在这里，我们证明了A3上调了谷胱甘肽S-转移酶（GST），谷胱甘肽（GSH）等内源性抗氧化酶，并逆转了缺血性卒中诱发的一氧化氮（NO）和脂质过氧化（LPO）升高。 -梗塞皮层和纹状体组织，通过激活内源性抗氧化剂核因子E2相关因子或核因子类红细胞2（Nrf2）。此外，A3减弱了神经炎症标记，例如离子钙结合衔接子分子1（Iba-1），环氧合酶2（COX-2），肿瘤坏死因子α（TNF-α），toll​​样受体（TLR4）免疫组化结果证明，通过下调p-JNK可以抑制核因子-κB（NF-κB）和核因子-κB（NF-κB）。此外，用A3治疗可减少梗塞面积和神经行为缺陷。我们采用了ATRA来拮抗Nrf2，后者取消了A3的神经保护作用，以进一步评估Nrf2途径的可能参与，如梗死增加和炎症标志物过度表达所证明。总之，我们的发现表明A3可以激活Nrf2，从而调节下游的抗氧化剂，