Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (12): 3430-3447.doi: 10.4103/NRR.NRR-D-24-01049

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Functional abnormalities of the glymphatic system in cognitive disorders

Wuyue Shentu1, #, Qi Kong2, #, Yier Zhang1 , Wenyao Li3 , Qiulu Chen4 , Sicheng Yan5 , Junjun Wang2 , Qilun Lai2 , Qi Xu6, *, Song Qiao2, *   

  1. 1 The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China;  2 Department of Neurology, Zhejiang Hospital, Hangzhou, Zhejiang Province, China;  3 Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China;  4 Department of Neurology, Zhejiang Medical & Health Group Hangzhou Hospital, Hangzhou, Zhejiang Province, China;  5 Department of Neurology, Liuzhou People’s Hospital, Liuzhou, Guangxi Zhuang Autonomous Region, China;  6 Department of Radiology, Zhejiang Hospital, Hangzhou, Zhejiang Province, China
  • Online:2025-12-15 Published:2025-03-13
  • Contact: Song Qiao, MD, qiaosong@zju.edu.cn; Qi Xu, MD, 285502508@qq.com.
  • Supported by:
    This work was supported by Zhejiang Provincial Medical and Health Science and Technology Project, Nos. 2022KY008 (to JW), 2023KY001 (to JW), 2023KY006 (to QL) and Zhejiang Provincial Traditional Chinese Medicine Science and Technology Project, No. 2023ZL220 (to QL).

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Abstract: Various pathological mechanisms represent distinct therapeutic targets for cognitive disorders, but a balance between clearance and production is essential for maintaining the stability of the brain’s internal environment. Thus, the glymphatic system may represent a common pathway by which to address cognitive disorders. Using the established model of the glymphatic system as our foundation, this review disentangles and analyzes the components of its clearance mechanism, including the initial inflow of cerebrospinal fluid, the mixing of cerebrospinal fluid with interstitial fluid, and the outflow of the mixed fluid and the clearance. Each section summarizes evidence from experimental animal models and human studies, highlighting the normal physiological properties of key structures alongside their pathological manifestations in cognitive disorders. The same pathologic manifestations of different cognitive disorders appearing in the glymphatic system and the same upstream influences are main points of interest of this review. We conclude this article by discussing new findings and outlining the limitations identified in current research progress.

Key words: aquaporin-4, astrocyte, cerebrospinal fluid dynamics, cognitive disorders, glymphatic system