Stamova Boryana, Knepp Bodie, Rodriguez Fernando
Department of Neurology, School of Medicine, University of California at Davis, Sacramento, CA, USA.
J Cereb Blood Flow Metab. 2025 Mar 13:271678X251322598. doi: 10.1177/0271678X251322598.
Stroke is a multifaceted disease with genetic and environmental components like diet and lifestyle. The central nervous and immune systems display complex interactions, with the peripheral immune response participating in brain injury and repair mechanisms following stroke. The bidirectional communication between the injured brain and peripheral blood presents an opportunity to investigate the molecular changes in the latter. There is substantial heterogeneity in stroke pathogenesis, pathophysiology, comorbidities, and response to treatment and outcome. This is captured and underscored by heterogeneity in the peripheral blood transcriptome. The current review highlights the role of the human peripheral blood transcriptome architecture for molecular phenotyping of different stroke etiologies and comorbidities, and for identifying underlying molecular correlates with clinically important variables and outcomes. Specific transcriptome features can potentially provide targets for clinical translation and for prioritizing genes and pathways for evaluation in experimental models. We also propose an approach to study the patient-specific transcriptional architecture and uncover the combinatorial heterogeneity in altered pathways in stroke patients that can also guide the search for treatment and prevention targets. Deciphering the molecular heterogeneity of stroke in a tissue that can be easily accessed and monitored, such as peripheral blood, may improve clinical trial success.
中风是一种具有遗传和环境因素（如饮食和生活方式）的多方面疾病。中枢神经系统和免疫系统表现出复杂的相互作用，外周免疫反应参与中风后的脑损伤和修复机制。受损大脑与外周血之间的双向交流为研究外周血中的分子变化提供了机会。中风的发病机制、病理生理学、合并症以及对治疗和预后的反应存在很大的异质性。外周血转录组的异质性体现并强调了这一点。本综述强调了人类外周血转录组结构在不同中风病因和合并症的分子表型分析以及识别与临床重要变量和预后相关的潜在分子关联方面的作用。特定的转录组特征可能为临床转化以及在实验模型中评估基因和通路的优先级提供靶点。我们还提出了一种研究患者特异性转录结构并揭示中风患者改变的通路中的组合异质性的方法，这也可以指导寻找治疗和预防靶点。在诸如外周血这样易于获取和监测的组织中解读中风的分子异质性，可能会提高临床试验的成功率。
