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1.Institute of Materiobiology, College of Sciences, Shanghai University, Shanghai 200444, China
2.Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China
3.University of Chinese Academy of Sciences, Beijing 100049, China
4.Department of Traumatology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China
收稿:2025-12-01,
修回:2026-03-12,
网络首发:2026-07-29,
纸质出版:2026-07-15
王苗苗,甘露,凡怡茹等.血脑屏障通透性评估技术进展:从仿生模型到多模态成像[J].浙江大学学报(英文版)(B辑:生物医学和生物技术),2026,27(07):715-735.
Miaomiao WANG, Lu GAN, Yiru FAN, et al. Blood‒brain barrier permeability assessment: from biomimetic models to multimodal imaging[J]. Journal of Zhejiang University-SCIENCE B, 2026, 27(7): 715-735.
王苗苗,甘露,凡怡茹等.血脑屏障通透性评估技术进展:从仿生模型到多模态成像[J].浙江大学学报(英文版)(B辑:生物医学和生物技术),2026,27(07):715-735. DOI: 10.1631/jzus.B2500786.
Miaomiao WANG, Lu GAN, Yiru FAN, et al. Blood‒brain barrier permeability assessment: from biomimetic models to multimodal imaging[J]. Journal of Zhejiang University-SCIENCE B, 2026, 27(7): 715-735. DOI: 10.1631/jzus.B2500786.
血脑屏障(BBB)是维持中枢神经系统内环境稳态的核心结构,其通透性调控失衡是脑卒中、神经退行性疾病和脑肿瘤等多种神经系统疾病的关键病理环节,也是中枢神经系统药物递送的主要瓶颈。因此,发展精准的BBB通透性检测技术,对于揭示神经疾病机制、突破药物研发瓶颈及推动精准诊疗至关重要。本文系统梳理了BBB通透性检测技术的最新进展:体外模型方面,概述了从传统Transwell体系到整合流体剪切力的微流控芯片及高度仿生类器官模型的演进,重点评价其对神经血管单元微环境模拟能力的提升;活体成像技术方面,深入分析了动态对比增强磁共振成像、正电子发射断层扫描、近红外二区荧光成像及双光子显微镜等技术的原理与应用,阐述了其在宏观定量、分子靶向及微观动态观测等方面的互补优势。多模态技术融合与精准量化评估是当前主要发展趋势。未来研究将聚焦于人工智能驱动的个性化BBB通透性评估、新型智能化探针开发以及BBB功能的实时动态监测,从而为神经系统疾病研究提供更强大的方法学工具。
The blood‒brain barrier (BBB) is a vital physiological structure that maintains the microenvironmental homeostasis in the central nervous system (CNS). Imbalances in its permeability play a key role in various neurological disorders
including stroke
neurodegenerative diseases
and brain tumors. The development of precise techniques for assessing BBB permeability is therefore paramount for elucidating the mechanisms of neurological diseases
overcoming drug development challenges
and achieving precise diagnosis and treatment of CNS disorders. This review systematically summarizes the latest advances in the assessment of BBB permeability. Regarding in vitro models
platforms have evolved from the traditional transwell system to microfluidic chips incorporating fluid shear forces and subsequently to highly biomimetic brain organoids
with continuous improvements in the ability to simulate the neurovascular unit (NVU) microenvironment. For in vivo assessment
we detail the principles and applications of imaging techniques
including dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)
positron emission tomography (PET)
near-infrared II (NIR-II) fluorescence imaging (FI)
and two-photon microscopy (TPM)
highlighting their complementary strengths in macroscopic quantification
molecular targeting
and microscopic dynamic observation. The integration of multi-modal technologies and precise quantitative assessment is a prominent trend. Future investigations will focus on artificial intelligence (AI)-driven personalized permeability assessment
the development of novel intelligent probes
and the dynamic real-time monitoring of the BBB
thereby providing powerful methodological support for neurological disease research.
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