TY  - JOUR
AU  - Han, Hongbin
AU  - Dai, Hui
AU  - Lopes, Leonor Serrano
AU  - Ni, Ruiqing
AU  - Combes, Benjamin F.
AU  - Song, Yangjing
AU  - Tan, Hanbo
AU  - Xu, Meng
AU  - Li, Hongfeng
AU  - Lv, Shuhong
AU  - Yang, Zhaohe
AU  - Gao, Tianzi
AU  - Zhang, Mengyu
AU  - Shi, Yang
AU  - Shao, Jingjing
AU  - Zhang, Yanni
AU  - Fu, Wanyi
PY  - 2026
TI  - Brain Extracellular Space: From an Overlooked Dimension to Catalyst of a Novel Neuroscience Paradigm
JO  - Cyborg and Bionic Systems
SN  - 2097-1087
SP  - 0529
VL  - 7
AB  - Despite huge investment, therapies for brain disorders remain largely ineffective in clinical practice. Accumulating evidence indicates that this low translational success is closely linked to the long-standing overlook of the brain extracellular space (ECS) in preclinical research, clinical practice, and regulatory frameworks. After over 4 decades of scientific exploration, particularly with recent breakthroughs in imaging and quantitative measurement methods, it is timely to integrate the ECS into the current neuroscience framework. This paper investigates underlying determinants of low translational success of central nervous system drugs and therapeutic devices, reviews the historical and technical bottlenecks that lead to the neglect of ECS research, and emphasizes its transformative potential in reshaping therapeutic strategies. We propose incorporating the ECS into neuroscience research, clinical regulatory assessment, and medical education, thereby establishing a comprehensive paradigm that omits no physical space for precision therapeutics targeting brain disorders.
UR  - https://doi.org/10.34133/cbsystems.0529
DO  - 10.34133/cbsystems.0529