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

Abstract

To clarify whether peripheral inflammation has a remote effect on the central nervous system, the electrolyte disposition between the circulating blood and central nervous system was evaluated in rats with carrageenan-induced acute peripheral inflammation (API). λ-Carrageenan was subcutaneously injected in the hind paw of the rat, and lithium was utilized as a surrogate marker of sodium. When the plasma and cerebrospinal fluid (CSF) concentrations of lithium were examined following lithium being intravenously administered, it was revealed that the CSF concentration of lithium in API rats is reduced compared to that in normal rats, while the plasma concentration profile of lithium in API rats is indistinguishable from that in normal rats. The pharmacokinetic analysis showed that the lithium disposition from the plasma to CSF markedly decreased by 35.8% in API rats compared to that in normal rats. On the other hand, when lithium was immediately administered into the lateral ventricle, its elimination profiles in CSF were not different between normal and API rats. It is therefore probable that the lithium disposition from the plasma to CSF alters in API rats, reflecting the entry process of electrolytes from the circulating blood to brain tissue being suppressed in response to peripheral inflammation.

<i>In Vivo</i> Study on Mechanism Underlying Increased Pharmacological Effects of Phenobarbital in Rats with Glycerol-Induced Acute Renal Failure

“…After 24-h acclimatization, each rat underwent surgical cannula insertion using a previously reported method. 10) In brief, the rat was fixed to a stereotaxic instrument (Model SR-5N, Narishige, Tokyo, Japan) under anesthetization with sodium pentobarbital (80 mg/kg, intraperitoneal injection (i.p.)). Then, a hole of 1 mm in diameter was made by drilling the skull, paying close attention to avoid damaging the brain tissue.…”

“…ARF induction was assessed based on elevation of the serum creatinine concentration and plasma AGP level. 7,10) The creatinine concentration was conventionally assessed with the Jaffe reaction. The AGP level was examined by Western blotting, as described later.…”

“…To overcome this interference by minimizing the ARF-related alteration of drug disposition in the brain tissues, we utilized a cannula insertion approach, in which the compound was immediately and continuously infused into the lateral ventricle via a surgically inserted cannula. 8,9) With this approach, we examined phenobarbital-induced anesthetization in ARF rats, and assessed whether the cerebral susceptibility to phenobarbital differed by comparing the phenobarbital amounts required to induce anesthesia between sham and ARF rats. We also evaluated the effects of ARF on the cerebral expression of the GABA A receptor and the cation-chloride transporters KCC2 and NKCC1 to elucidate the mechanism underlying the increased pharmacological effects following renal impairment.…”

Effect of Carrageenan-induced Acute Peripheral Inflammation on the Pharmacokinetics and Hepatic Metabolism of Midazolam in Rats

“…Induction of API in rats: API was induced in rats withcarrageenan treatment, as previously reported. 21) Briefly, after being anesthetized with pentobarbital (50 mg/kg, i.p. ), rats were treated with -carrageenan solution prepared at a concentration of 40 mg/ml with phosphate-buffered saline (PBS).…”

“…The rats were then subjected to experiments following a 24-h rest period. 21) Evaluation of plasma concentration profiles of MDZ and its metabolites in rats: After being anesthetized with pentobarbital, a male rat was fixed on its back, and the right femoral artery was cannulated with polyethylene tubing (SP-31, Natsume Seisakusho, Tokyo, Japan) for blood collection. The polyethylene tubing was heparinized to prevent coagulation.…”