State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Exp Neurol. 2024 Nov;381:114942. doi: 10.1016/j.expneurol.2024.114942. Epub 2024 Aug 31.
Ischemic stroke has garnered global medical attention as one of the most serious cerebrovascular diseases. The mechanisms involved in both the development and recovery phases of ischemic stroke are complex, involving intricate interactions among different types of cells, each with its own unique functions. To better understand the possible pathogenesis, neurovascular unit (NVU), a concept comprising neurons, endothelial cells, mural cells, glial cells, and extracellular matrix components, has been used in analysing various brain diseases, particularly in ischemic stroke, aiming to depict the interactions between cerebral vasculature and neural cells. While in vivo models often face limitations in terms of reproducibility and the ability to precisely mimic human pathophysiology, it is now important to establish in vitro NVU models for ischemic stroke research. In order to accurately portray the pathological processes occurring within the brain, a diverse array of NVU 2D and 3D in vitro models, each possessing unique characteristics and advantages, have been meticulously developed. This review presents a comprehensive overview of recent advancements in in vitro models specifically tailored for investigating ischemic stroke. Through a systematic categorization of these developments, we elucidate the intricate links between NVU components and the pathogenesis of ischemic stroke. Furthermore, we explore the distinct advantages offered by innovative NVU models, notably 3D models, which closely emulate in vivo conditions. Additionally, an examination of current therapeutic modalities for ischemic stroke developed utilizing in vitro NVU models is provided. Serving as a valuable reference, this review aids in the design and implementation of effective in vitro models for ischemic stroke research.
缺血性脑卒中是全球关注的最严重的脑血管疾病之一。缺血性脑卒中的发生和恢复阶段的机制非常复杂，涉及不同类型的细胞之间复杂的相互作用，每种细胞都有其独特的功能。为了更好地了解可能的发病机制，神经血管单元（NVU）概念被用于分析各种脑疾病，特别是缺血性脑卒中，旨在描述脑血管和神经细胞之间的相互作用。虽然体内模型在重现性和精确模拟人类生理学方面经常面临限制，但现在建立用于缺血性脑卒中研究的体外 NVU 模型非常重要。为了准确描绘大脑内部发生的病理过程，已经精心开发了各种具有独特特征和优势的 NVU 2D 和 3D 体外模型。这篇综述全面介绍了专门用于研究缺血性脑卒中的体外模型的最新进展。通过对这些进展进行系统分类，我们阐明了 NVU 成分与缺血性脑卒中发病机制之间的复杂联系。此外，我们探讨了创新的 NVU 模型（特别是 3D 模型）提供的独特优势，这些模型非常接近体内条件。还对利用体外 NVU 模型开发的缺血性脑卒中的当前治疗方法进行了考察。作为有价值的参考，这篇综述有助于设计和实施有效的缺血性脑卒中研究的体外模型。
