Li Yuanyuan, Han Hongbin, Shi Kuangyu, Cui Dehua, Yang Jun, Alberts Ian Leigh, Yuan Lan, Zhao Guomei, Wang Rui, Cai Xianjie, Teng Ze
1Department of Radiology, Peking University Third Hospital, Beijing, China.
2Beijing Key Laboratory of Magnetic Resonance Imaging Equipment and Technique, Beijing, China.
Aging Dis. 2020 Dec 1;11(6):1407-1422. doi: 10.14336/AD.2020.0224. eCollection 2020 Dec.
The drainage of brain interstitial fluid (ISF) has been observed to slow down following neuronal excitation, although the mechanism underlying this phenomenon is yet to be elucidated. In searching for the changes in the brain extracellular space (ECS) induced by electrical pain stimuli in the rat thalamus, significantly decreased effective diffusion coefficient (D) and volume fraction (α) of the brain ECS were shown, accompanied by the slowdown of ISF drainage. The morphological basis for structural changes in the brain ECS was local spatial deformation of astrocyte foot processes following neuronal excitation. We further studied aquaporin-4 gene () knockout rats in which the changes of the brain ECS structure were reversed and found that the slowed D and ISF drainage persisted, confirming that the down-regulation of ISF drainage following neuronal excitation was mainly attributable to the release of neurotransmitters rather than to structural changes of the brain ECS. Meanwhile, the dynamic changes in the D were synchronized with the release and elimination processes of neurotransmitters following neuronal excitation. In conclusion, the downregulation of ISF drainage following neuronal excitation was found to be caused by the restricted diffusion in the brain ECS, and D mapping may be used to track the neuronal activity in the deep brain.
尽管神经元兴奋后脑间质液（ISF）引流减缓这一现象的潜在机制尚待阐明，但已有观察发现这种情况会出现。在探寻大鼠丘脑电刺激诱发的脑细胞外间隙（ECS）变化时，研究显示脑ECS的有效扩散系数（D）和体积分数（α）显著降低，同时伴有ISF引流减缓。脑ECS结构变化的形态学基础是神经元兴奋后星形胶质细胞足突的局部空间变形。我们进一步研究了水通道蛋白-4基因（）敲除大鼠，其中脑ECS结构的变化得以逆转，结果发现D减慢和ISF引流减缓仍持续存在，这证实了神经元兴奋后ISF引流的下调主要归因于神经递质的释放，而非脑ECS的结构变化。同时，D的动态变化与神经元兴奋后神经递质的释放和消除过程同步。总之，研究发现神经元兴奋后ISF引流的下调是由脑ECS中扩散受限所致，并且D图谱可用于追踪深部脑区的神经元活动。
