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微环境“时空梯度”对血脑屏障功能的调控及帕金森病的病理演变:微流控芯片的独特优势

Regulation of BBB function and pathological evolution of PD by microenvironment "spatiotemporal gradient": unique advantages of microfluidic chips.

作者信息

Yu Sixun, Jiang Lingli, Song Min, Yang Tao, Yuan Ma, Chen Xin, Shu Haifeng

机构信息

Department of Neurosurgery, Western Theater General Hospital, Chengdu, China.

出版信息

Front Aging Neurosci. 2025 Jul 9;17:1599509. doi: 10.3389/fnagi.2025.1599509. eCollection 2025.

Abstract

Parkinson's disease (PD), a prevalent neurodegenerative disorder, exhibits an exceedingly intricate pathological process characterized by multifaceted neuronal loss, inflammatory responses, protein misfolding, and blood-brain barrier (BBB) dysfunction. In the pathogenesis of PD, the BBB serves not only as a protective interface for the central nervous system but also actively contributes to the regulation of neural microenvironment homeostasis. Consequently, its impaired functionality can markedly exacerbate disease progression. Within the microenvironment, factors such as chemical gradients, fluid shear stress, and physical-mechanical signals play pivotal roles in modulating cellular behavior and organ function. The spatiotemporal dynamics of these gradients critically influence BBB integrity and neuroinflammatory responses. However, traditional models struggle to faithfully replicate such multidimensional dynamic microenvironmental changes. Recently, microfluidic chip technology has emerged as a transformative platform capable of simulating conditions through precise control of microenvironmental spatiotemporal gradients. This review examines the advancements of microfluidic chips in reproducing dynamic microenvironment gradients, regulating BBB function, and elucidating the pathological evolution of PD. It delves into the fundamental principles of microfluidic technology, gradient generation and control methodologies, and provides examples of BBB organoid models and PD pathological environment simulations constructed on this platform. Additionally, it systematically evaluates the technical bottlenecks, standardization challenges, and data integration issues associated with current model development, while exploring the potential for future technological convergence and interdisciplinary collaboration in advancing PD precision simulation and personalized treatment.

摘要

帕金森病(PD)是一种常见的神经退行性疾病,其病理过程极其复杂,具有多方面的神经元损失、炎症反应、蛋白质错误折叠和血脑屏障(BBB)功能障碍等特征。在PD的发病机制中,血脑屏障不仅作为中枢神经系统的保护界面,还积极参与神经微环境稳态的调节。因此,其功能受损会显著加剧疾病进展。在微环境中,化学梯度、流体剪切应力和物理机械信号等因素在调节细胞行为和器官功能方面起着关键作用。这些梯度的时空动态变化对血脑屏障的完整性和神经炎症反应有着至关重要的影响。然而,传统模型难以如实复制这种多维动态微环境变化。最近,微流控芯片技术已成为一个变革性平台,能够通过精确控制微环境的时空梯度来模拟各种条件。本文综述了微流控芯片在再现动态微环境梯度、调节血脑屏障功能以及阐明PD病理演变方面的进展。探讨了微流控技术的基本原理、梯度生成和控制方法,并提供了在此平台上构建的血脑屏障类器官模型和PD病理环境模拟的实例。此外,系统评估了当前模型开发中存在的技术瓶颈、标准化挑战和数据整合问题,同时探讨了未来技术融合和跨学科合作在推进PD精准模拟和个性化治疗方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53b7/12283772/bbf70e6a0cee/fnagi-17-1599509-g001.jpg

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