Brain active transmembrane water cycling measured by MR is associated with neuronal activity(2018). DOI: 10.1002/mrm.27473CV.pdf
We found that neurons absorb and release water when they relay messages throughout the brain. Tracking this water movement with imaging technology may one day provide valuable information on normal brain activity, as well as how injury or disease affect brain function.
Current functional magnetic resonance imaging (fMRI) technologies measure neuronal activity indirectly by tracking changes in blood flow and blood oxygen levels. Neurons communicate with each other by a process known as firing. In this process, they emit a slight electrical charge as an enzyme moves positively charged molecules — potassium and sodium ions — through the cell membrane. In the current study, when we stimulated cell cultures of rat neurons to fire, we found that the exchanges of potassium and sodium ions was accompanied by an increase in the number of water molecules moving into and out of the cell.
We noted that our method works only in cultures of neurons and additional studies are necessary to advance the technology so that it can be used to monitor neuronal firing in living organisms.
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, [Cai2+] 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.
active, fMRI, functional MRI, membrane, transcytolemmal, Na+/K+ ATPase, neuronal activity, pump, water exchange
Online paper: https://doi.org/10.1002/mrm.27473