NMR Studies of Intra- and Extracellular Red Blood Cell Lithium by Transverse Relaxation Measurements and Shift Reagents

Lithium salts are used in the treatment and prophylaxis of bipolar or mood disorders. The mechanism of action by which the cation exerts its therapeutic influence is unknown. A knowledge of brain Li concentration, its distribution in the brain, and its properties in the cellular microenvironment may have a strong influence on the understanding of Li function. The differentiation of lithium in the intra and extracellular environments has been achieved in a noninvasive manner in red blood cell (RBC) model. The two distinct transverse relaxation (T2) components have been observed in the blood sample drawn from lithium treated rats. These results indicate two different environments for Li with a fast (T2f) and a slow (T2s) component in the RBC model corresponding fractions that contribute to each relaxation component. The results compare well with the intra- and extracellular RBC lithium measured using shift reagents. Our studies indicate that the T2 method has utility in estimating the intracellular Li in systems that exhibit similar T2 behavior. The studies performed at different Li doses in the rat model indicate that the method may have utility in following a wide range of intracellular Li.