《生命科学》 2026, 38(8): 1483-1499

脑血管功能障碍驱动中枢神经系统疾病的机制

卢瑾瑾^1,2 , 杨 晓^1,2,*

¹国家蛋白质科学中心（北京），医学蛋白质组学全国重点实验室，北京 102206 ²清华大学基础医学院， 北京 100084

摘　要：

长期以来，脑血管功能障碍被视为中枢神经系统疾病的继发或伴随现象。然而，近年来的研究表明，脑血管功能障碍在中枢神经系统疾病发生发展过程中具有关键的驱动作用。脑血管功能障碍如血流动力学紊乱、血脑屏障破坏、转运与清除功能受损以及血管旁分泌信号紊乱，可通过破坏微环境稳态、神经血管通讯及诱发神经免疫炎症级联反应等，促进多种中枢神经系统疾病的病理进程。本文系统总结脑血管功能在中枢神经系统生理与病理过程中的关键作用，并结合多组学及影像学等技术进展，探讨靶向脑血管的中枢神经系统疾病精准干预策略。

通讯作者：杨 晓 , Email:yangx@bmi.ac.cn

Mechanisms underlying cerebrovascular dysfunction in driving central nervous system diseases

LU Jin-Jin^1,2 , YANG Xiao^1,2,*

¹State Key Laboratory of Medical Proteomics, National Center for Protein Sciences (Beijing), Beijing 102206, China ²School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China

Abstract:

Cerebrovascular dysfunction has long been regarded as a secondary or accompanying phenomenon in central nervous system (CNS) diseases. However, accumulating evidence from clinical, genetic, and experimental studies now indicates that vascular abnormalities actively contribute to the initiation and progression of a wide spectrum of CNS disorders. Cerebrovascular dysfunction, including cerebral hypoperfusion, disruption of the blood-brain barrier (BBB), impaired  transport and clearance across the cerebrovascular interface, and dysregulated vascular paracrine signaling, can profoundly disturb neural microenvironmental homeostasis, compromise neurovascular communication, and trigger maladaptive neuroimmune and inflammatory cascades. These processes collectively accelerate neuronal dysfunction, compromise synaptic  homeostasis, and drive neurodegeneration. This review systematically summarizes the essential physiological roles of the  cerebrovasculature within the neurovascular unit (NVU), highlighting its contributions to neural development and the  maintenance of CNS microenvironmental homeostasis through tightly regulated BBB transport of nutrients and metabolites, activity-dependent neurovascular coupling, and perivascular glymphatic clearance of metabolic waste. We then explore the pathological mechanisms by which cerebrovascular dysfunction drives CNS disease across five core dimensions:  hemodynamic disturbances, which trigger neuronal energy crises, ionic imbalances, and excitotoxicity; BBB disruption,  which permits the infiltration of neurotoxic plasma proteins (e.g., fibrinogen, thrombin) and peripheral immune cells;  dysfunction of transport and clearance systems, leading to the accumulation of metabolic waste and pathogenic proteins such as amyloid-β and Tau; aberrant vascular paracrine signaling, which disrupts the intercellular crosstalk essential for neural  development, synaptic plasticity, and inflammatory regulation; and neuroimmune inflammation, wherein vascular defects initiate self-perpetuating cascades that accelerate neuronal death. Finally, we highlight the translational potential of the  cerebrovasculature as both a gateway for systemic interventions and an early indicator of CNS pathology. In the initial stages of disease, high-resolution vascular imaging can reveal subtle vascular abnormalities, while spatial multi-omics approaches  map cerebrovascular heterogeneity to uncover actionable therapeutic targets. These macro- and micro-scale insights provide  the basis for emerging precision medicine strategies, from imaging-guided patient stratification to combinatorial interventions  aimed at restoring NVU integrity. Collectively, this review positions the cerebrovasculature as a key driver of CNS pathology  and a promising target for early diagnosis and disease-modifying therapies.

Communication Author：YANG Xiao , Email:yangx@bmi.ac.cn