The blood-cerebrospinal fluid barrier is a major pathway of cerebral creatinine clearance: Involvement of transporter-mediated process

Masanori Tachikawa, Yasuyuki Kasai, Masato Takahashi, Jun Fujinawa, Kiyoyuki Kitaichi, Tetsuya Terasaki, Ken Ichi Hosoya

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

There is still incomplete evidence for the cerebral clearance of creatinine (CTN) which is an endogenous convulsant and accumulates in the brain and CSF of patients with renal failure. The purpose of this study was to clarify the transporter-mediated CTN efflux transport from the brain/CSF. In vivo data demonstrated that CTN after intracerebral administration was not significantly eliminated from the brain across the blood-brain barrier. In contrast, the elimination clearance of CTN from the CSF was 60-fold greater than that of inulin, reflecting CSF bulk flow. Even in renal failure model rats, the increasing ratio of the CTN concentration in the CSF was lower than that in the plasma, suggesting a significant role for the CSF-to-blood efflux process. The inhibitory effects of inhibitors and antisense oligonucleotides on CTN uptake by isolated choroid plexus indicated the involvement of rat organic cation transporter 3 (rOCT3) and creatine transporter (CRT) in CTN transport. rOCT3- and CRT-mediated low-affinity CTN transport with Km values of 47.7 and 52.0 mM, respectively. Our findings suggest that CTN is eliminated from the CSF across the blood-CSF barrier as a major pathway of cerebral CTN clearance and transporter-mediated processes are involved in the CTN transport in the choroid plexus.

Original languageEnglish
Pages (from-to)432-442
Number of pages11
JournalJournal of Neurochemistry
Volume107
Issue number2
DOIs
Publication statusPublished - 2008 Oct

Keywords

  • Blood-cerebrospinal fluid barrier
  • Cerebral clearance
  • Creatine transporter
  • Creatinine
  • Organic cation transporter
  • Renal failure

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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