Regulation of lithium in cerebrospinal fluid by the in situ isolated choroid plexus of the cat

It is well established that the choroid plexus is a major site of c.s.f. production and for regulating die composition of the c.s.f. The in situ isolated choroid plexus preparation provides a unique system with which to study the role of the choroid plexus in the ^ regulation of ion transport from blood to c.s.f. and vice versa. The concentration of lithium in the interstitial fluid of brain is known to affect the function of the brain. Measurement of the c.s.f. concentration of lithium serves as a gross reflection of the lithium concentration in the extracellular fluid of the C.N.S. The role of the choroid plexus in regulation of lithium concentration in the c.s.f. with and without alterations in c.s.f. and plasma levels of this ion was studied. The change in concentration of lithium in the chamber fluid was about 0.58 m-equiv/1. for each 1 m-equiv/l, change in plasma concentration of lithium in response to the infusion of a 154 mM LiCl solution. The lithium concentration in chamber fluid was maintained at 53% to 60% of plasma levels when the plasma lithium concentrations varied over the therapeutic and the toxic range in man. The concentration of lithium reached a steady state in plasma and in c.s,f. at about 90 min after the start of a constant intravenous infusion of LlCl solution. This shows that the slow onset of action of lithium in the treatment of manic depression is not due to the inability of lithium to cross the blood-c.s.f. barrier. The concentration of lithium in the chamber fluid decreased during the 30 min collection period when either low or high lithium in artificial c.s.f. was added to the chamber. The magnitude of the decrease is independent of the direction of the gradient between plasma and c.s.f. over the range studied. This indicates that dilution by newly formed fluid is a major factor in reducing the concentration of lithium in the chamber. It is reduced secondarily by passive diffusion. The change in the concentration of potassium on the c.s.f. side of the choroid plexus induced appropriate alterations in the new c.s.f. potassium to bring the concentration of potassium in the chamber fluid toward a normal value. Lithium appears to be transported by the same system that regulates c.s.f. potassium. However, the system is much more selective for potassium. These results support the concept that lithium is transported to a limited extent by sodium pumps and also diffuses passively. The mechanisms underlying the therapeutic usefulness of lithium in mania are not known. The in situ isolated choroid piexus in cats was used to investigate the effect of varying the lithium concentration in plasma and in c.s.f. on the concentration of electrolytes in the c.s.f. The concentration of magnesium in plasma was 2.7 m-equiv/1. or more, while chamber fluid magnesium was not affected. The chamber fluid to plasma ratio of 22Na is greater than unity after a 90 min infusion of 22NaCl solution. The total amount of 22Na in the chamber fluid significantly increased when lithium (1.5 m-equiv/l.) or high-potassium (6.6 m-equiv/1.) artificial c.s.f. was added to the chamber; there is no difference in 22Na activity between the control and the experimental group in which 50 µl of normal artificial c.s.f. was added to the chamber. Ouabain (10[-3] M) significantly inhibited the stimulatory effect of lithium or high-potassium on the rate of 22Na transport from blood to c.s.f. and also reduced the rate of c.s.f. secretion. The entry of 22Na into the chamber was not affected by plasma lithium levels corresponding to the subtherapeutic to therapeutic levels in man. The present experiments suggest that lithium is transported by systems that normally transport sodium into the c.s.f. to produce the fluid and transport potassium out of c.s.f. in exchange for sodium. There is also a significant diffusional component.