Hu Ziliang, Zhao Mingyue, Shen Hangyu, Wei Liangzhe, Sun Jie, Gao Xiang, Huang Yi
Department of Neurosurgery, Ningbo Key Laboratory of Nervous System and Brain Function, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, China.
Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, Zhejiang Province, China.
Neural Regen Res. 2026 Apr 1;21(4):1483-1496. doi: 10.4103/NRR.NRR-D-24-01404. Epub 2025 Mar 25.
Strokes include both ischemic stroke, which is mediated by a blockade or reduction in the blood supply to the brain, and hemorrhagic stroke, which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain. Stroke is a life-threatening cerebrovascular condition characterized by intricate pathophysiological mechanisms, including oxidative stress, inflammation, mitochondrial dysfunction, and neuronal injury. Critical transcription factors, such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B, play central roles in the progression of stroke. Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage, inflammatory responses, and cytotoxic agents. It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function, endoplasmic reticulum stress, and lysosomal activity and regulating metabolic pathways and cytokine expression. Conversely, nuclear factor-kappaB is closely associated with mitochondrial dysfunction, the generation of reactive oxygen species, oxidative stress exacerbation, and inflammation. Nuclear factor-kappaB contributes to neuronal injury, apoptosis, and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators. The interplay between these pathways, potentially involving crosstalk among various organelles, significantly influences stroke pathophysiology. Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted, individualized, cell type-specific treatments. In this review, we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke, with an emphasis on their roles in oxidative stress, inflammation, and neuroprotection.
中风包括缺血性中风和出血性中风，前者是由大脑血液供应受阻或减少介导的，后者包括脑出血和蛛网膜下腔出血，其特征是脑内出血。中风是一种危及生命的脑血管疾病，其病理生理机制复杂，包括氧化应激、炎症、线粒体功能障碍和神经元损伤。关键转录因子，如核因子红细胞2相关因子2（Nrf2）和核因子κB（NF-κB），在中风进展中起核心作用。Nrf2对细胞氧化还原状态的变化敏感，在保护细胞免受氧化损伤、炎症反应和细胞毒性剂方面至关重要。它通过影响线粒体功能、内质网应激和溶酶体活性以及调节代谢途径和细胞因子表达，在中风后神经保护和修复中发挥重要作用。相反，NF-κB与线粒体功能障碍、活性氧生成、氧化应激加剧和炎症密切相关。NF-κB通过调节细胞粘附分子和炎症介质，促进中风后的神经元损伤、凋亡和免疫反应。这些途径之间的相互作用，可能涉及各种细胞器之间的串扰，显著影响中风的病理生理学。单细胞测序和空间转录组学的进展极大地提高了我们对中风发病机制的理解，并为开发靶向、个性化、细胞类型特异性治疗提供了新机会。在这篇综述中，我们讨论了Nrf2和NF-κB参与缺血性和出血性中风的潜在机制，重点关注它们在氧化应激、炎症和神经保护中的作用。
