中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (2): 433-442.doi: 10.4103/NRR.NRR-D-24-00821

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

大脑中的类淋巴通路:脑小血管疾病的新靶点?

  

  • 出版日期:2026-02-15 发布日期:2025-05-17
  • 基金资助:
    申康医院发展中心重大临床研究项目,编号:SHDC2020CR2046B;上海市卫生计生委人才计划,编号:2022LJ010。

Targeting the brain’s glymphatic pathway: A novel therapeutic approach for cerebral small vessel disease

Yuhui Ma, Yan Han*   

  1. Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
  • Online:2026-02-15 Published:2025-05-17
  • Contact: Yan Han, PhD, hanyan@shutcm.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 82274304 (to YH); the Major Clinical Study Projects of Shanghai Shenkang Hospital Development Center, No. SHDC2020CR2046B (to YH); and Shanghai Municipal Health Commission Talent Plan, No. 2022LJ010 (to YH).

摘要:

脑小血管病是一组以小血管损伤为特征的神经系统疾病,常导致脑卒中和痴呆。由于病因的多样性和病理机制的复杂性,脑小血管病的预防和治疗仍面临巨大挑战。近年来,人们发现类淋巴系统与间质溶质清除有关,并参与维持脑平衡。越来越多的证据表明,类淋巴清除功能障碍在脑小血管病的进展中起着关键作用。这篇综述首先全面介绍了类淋巴系统的结构、功能和驱动因素,指出了它在脑废物清除中的关键作用。随后,从类淋巴系统的角度重新审视了脑小血管病,并总结了类淋巴系统与脑小血管病之间的相关机制。糖代谢功能障碍可能导致代谢废物在脑内堆积,从而加剧脑小血管病的病理过程。在此基础上,文章详细讨论了两种亚型脑小血管病(动脉硬化脑小血管病和淀粉样蛋白相关脑小血管病)患者或动物模型中类淋巴系统功能障碍的直接证据。目前,沿血管周围空间扩散张量成像是评估淋巴样系统清除功能的重要非侵入性工具,但其参数的有效性仍有待提高。在包括脑小血管病在内的各种神经系统疾病中,脑功能衰竭可能是导致痴呆的常见最终途径。最后,文章总结了针对类淋巴排泄功能的预防和治疗策略,为未来开发新的脑小血管病疗法提供了可靠的思路。

https://orcid.org/0000-0002-7654-0906 (Yan Han)

关键词: 水通道蛋白4, 星形胶质细胞, 脑淀粉样血管病, 脑小血管病,  , 脑脊液,  , 沿血管周围空间的弥散张量图像, 淋巴系统, 间质, 血管周围空间, 治疗策略

Abstract: Cerebral small vessel disease encompasses a group of neurological disorders characterized by injury to small blood vessels, often leading to stroke and dementia. Due to its diverse etiologies and complex pathological mechanisms, preventing and treating cerebral small vessel vasculopathy is challenging. Recent studies have shown that the glymphatic system plays a crucial role in interstitial solute clearance and the maintenance of brain homeostasis. Increasing evidence also suggests that dysfunction in glymphatic clearance is a key factor in the progression of cerebral small vessel disease. This review begins with a comprehensive introduction to the structure, function, and driving factors of the glymphatic system, highlighting its essential role in brain waste clearance. Afterwards, cerebral small vessel disease was reviewed from the perspective of the glymphatic system, after which the mechanisms underlying their correlation were summarized. Glymphatic dysfunction may lead to the accumulation of metabolic waste in the brain, thereby exacerbating the pathological processes associated with cerebral small vessel disease. The review also discussed the direct evidence of glymphatic dysfunction in patients and animal models exhibiting two subtypes of cerebral small vessel disease: arteriolosclerosis-related cerebral small vessel disease and amyloid-related cerebral small vessel disease. Diffusion tensor image analysis along the perivascular space is an important noninvasive tool for assessing the clearance function of the glymphatic system. However, the effectiveness of its parameters needs to be enhanced. Among various nervous system diseases, including cerebral small vessel disease, glymphatic failure may be a common final pathway toward dementia. Overall, this review summarizes prevention and treatment strategies that target glymphatic drainage and will offer valuable insight for developing novel treatments for cerebral small vessel disease.

Key words: aquaporin-4,  , astrocytes,  , cerebral amyloid angiopathy,  , cerebral small vessel disease,  , cerebrospinal fluid,  , diffusion tensor image analysis along the perivascular space,  , glymphatic system,  , interstitial fluid,  , perivascular space,  , therapeutic strategies