Brain active transmembrane water cycling measured by MR is associated with neuronal activity

作者：Bai, Ruiliang; Springer, Charles S., Jr.; Plenz, Dietmar; Basser, Peter J.^*

来源：Magnetic Resonance in Medicine, 2019, 81(2): 1280-1295.

DOI：10.1002/mrm.27473

• active
• fMRI
• functional MRI
• membrane
• transcytolemmal
• Na+/K+ ATPase
• neuronal activity
• pump
• water exchange

Purpose: fMRI is widely used to study brain activity. Unfortunately, conventional fMRI methods assess neuronal activity only indirectly, through hemodynamic coupling. Here, we show that active, steady-state transmembrane water cycling (AWC) could serve as a basis for a potential fMRI mechanism for direct neuronal activity detection. @@@ Methods: AWC and neuronal actitivity in rat organotypic cortical cultures were simultaneously measured with a hybrid MR-fluorescence system. Perfusion with a paramagnetic MRI contrast agent, Gadoteridol, allows NMR determination of the kinetics of transcytolemmal water exchange. Changes in intracellular calcium concentration, [Ca-i(2+)] were used as a proxy of neuronal activity and were monitored by fluorescence imaging. @@@ Results: When we alter neuronal activity by titrating with extracellular [K+] near the normal value, we see an AWC response resembling Na+-K+-ATPase (NKA) Michaelis-Menten behavior. When we treat with the voltage-gated sodium channel inhibitor, or with an excitatory postsynaptic inhibitor cocktail, we see AWC decrease by up to 71%. AWC was found also to be positively correlated with the basal level of spontaneous activity, which varies in different cultures. @@@ Conclusions: These results suggest that AWC is associated with neuronal activity and NKA activity is a major contributor in coupling AWC to neuronal activity. Although AWC comprises steady-state, homeostatic transmembrane water exchange, our analysis also yields a simultaneous measure of the average cell volume, which reports any slower net transmembrane water transport.

• 出版日期2019-2
• 单位浙江大学