Altered electrolyte handling of the choroid plexus in rats with glycerol‐induced acute renal failure

Abstract

The altered electrolyte handling of the choroid plexus was investigated in rats with acute renal failure (ARF) using lithium and rubidium as surrogate markers for sodium and potassium, respectively. Firstly, the transport of these two markers from the plasma to cerebrospinal fluid (CSF) was evaluated after they were concurrently injected into the femoral vein. As a result, their disposition from the plasma to CSF was shown to decrease in ARF rats, but the relationship profile between those two markers was not different from that observed in normal rats, indicating that the decreased disposition of lithium and rubidium occurs without affecting the stoichiometric balance. To clarify the mechanisms accounting for the decreased disposition, an inhibition study was then performed. When bumetanide, an inhibitor of the Na(+) /K(+) /2Cl(-) co-transporter, was directly introduced into the cerebroventricle prior to lithium and rubidium being intravenously administered, a marked increase in the markers' disposition was observed. However, such an increased disposition did not occur when bumetanide was injected into the femoral vein. Other inhibitors, such as amiloride for the Na(+) /H(+) exchanger and ouabain for Na(+) /K(+) -ATPase, did not show any effects on marker disposition regardless of the inhibitor being administered into either the cerebroventricle or femoral vein. These findings suggest that the decreased marker disposition in ARF rats is due to an increased efflux process of the choroid plexus mediated by the Na(+) /K(+) /2Cl(-) co-transporter. That is, electrolyte efflux from the CSF to plasma increases, and thereby the electrolyte influx from the plasma to CSF is counteracted.

Effect of Carrageenan-Induced Acute Peripheral Inflammation on the Electrolyte Disposition to Cerebrospinal Fluid in Rats

“…The permeation coefficient was calculated by dividing the lithium concentration in the effluent by that in the donor solution. 14,15,20) The mean values and standard errors of the permeation coefficients for the probes used in the experiments with normal and API rats were 0.233± 0.021 and 0.233± 0.016, respectively, not being different between the groups.…”

“…17) Evaluation of the Lithium Disposition from the Plasma to CSF in Rats The lithium disposition from the plasma to CSF was evaluated by comparing their lithium concentration profiles as previously reported. 14,15) Briefly, to examine the lithium concentration profile in the plasma, each rat was fixed on its back after being anesthetized with pentobarbital, and the lithium chloride solution prepared at a concentration of 375 mM was gently administered into the right femoral vein with an infusion pump. The lithium dose administered was set as 0.75 mmol/kg, and the infusion rate was adjusted to 0.1 mL/ min.…”

“…The lithium concentration profile in CSF was evaluated using the microdialysis method as previously reported. 14,15) After a rat was anesthetized, the microdialysis probe assembly equipped with a semi-permeable cellulose membrane (A-I-8, Eicom, Kyoto, Japan) was inserted into the right lateral ventricle via the guide cannula, in which the tip of the probe was carefully located at the following brain atlas coordinates originating from the bregma: anterior, 0.0 mm; lateral, 1.5 mm; ventral, 3.2 mm. 19) The semi-permeable membrane was 1 mm in length and 200 µm in diameter, and its molecular permeation threshold was 50 kDa.…”

“…The lithium concentration in the collected effluent was determined as described later, and the lithium concentration in CSF was calculated, taking account of the permeation coefficient of the probe assembly that was determined prior to each experiment. 14,20) To determine the probe's permeation coefficient, the probe was first immersed in the lithium solution (donor solution) prepared at a concentration of 1 µg/mL (144 µM) with Ringer's solution. Its inlet and outlet tubes were connected to the syringe infusion pump and the fraction collector, respectively.…”

“…In this study, we examined the effect of peripheral inflammation on the electrolyte disposition between the plasma and CSF in rats, in which lithium was utilized as a surrogate marker of sodium, 12,13) and its concentration profile in CSF was monitored with a microdialysis probe placed in the lateral ventricle. 14,15) It is well known that lithium resembles to sodium regarding chemical properties and it is handled by various electrolyte transporters, such as SLC12A2/NKCC1 and SLC9A1/NHE1, in a similar manner to sodium. 12,13) To induce peripheral inflammation in rats, carrageenan administration was employed, 16) since this induction method has been established for decades, and there is only a remote chance that the subcutaneously administered carrageenan will contact the brain tissue directly.…”