Evidence map›Paper›PMID 20571525›Full record

ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2011

Distribution of glycylsarcosine and cefadroxil among cerebrospinal fluid, choroid plexus, and brain parenchyma after intracerebroventricular injection is markedly different between wild-type and Pept2 null mice.

David E Smith, Yongjun Hu, Hong Shen, Tavarekere N Nagaraja, Joseph D Fenstermacher, Richard F Keep

Open access · bronzeAbstract read
In one paragraph

Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.0field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 31 citations in OpenAlex.

  1. Review
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  4. Article
  5. Review
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  8. In vitro, in vivo and in silico models of drug distribution into the brain.Journal of pharmacokinetics and pharmacodynamics · 2013
    Review
  9. Article
  10. Article
  11. Article
  12. Choroid plexus transport: gene deletion studies.Fluids and barriers of the CNS · 2011
    Article
  13. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

David E SmithDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-5633, USA. smithb@umich.edu
Yongjun Hu
Hong Shen
Tavarekere N Nagaraja
Joseph D Fenstermacher
Richard F Keep
University of Michigan–Ann Arbor · USHenry Ford Health System · US

Funding

Role of PEPT2 in Peptide/Mimetic Disposition-DynamicsR01GM035498 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SMITH, DAVID E · 1988 to 2013
$3.7M
Endothelial Preconditioning and Ischemic Brain InjuryR01NS034709 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KEEP, RICHARD F · 1996 to 2013
$3.6M
NIGMS NIH HHS R01 GM035498NINDS NIH HHS R01 NS034709
6 · The paper itself

Abstract

The purpose of this study was to define the cerebrospinal fluid (CSF) clearance kinetics, choroid plexus uptake, and parenchymal penetration of PEPT2 substrates in different regions of the brain after intracerebroventricular administration. To accomplish these objectives, we performed biodistribution studies using [(14)C]glycylsarcosine (GlySar) and [(3)H]cefadroxil, along with quantitative autoradiography of [(14)C]GlySar, in wild-type and Pept2 null mice. We found that PEPT2 deletion markedly reduced the uptake of GlySar and cefadroxil in choroid plexuses at 60 mins by 94% and 82% (P<0.001), respectively, and lowered their CSF clearances by about fourfold. Autoradiography showed that GlySar concentrations in the lateral, third, and fourth ventricle choroid plexuses were higher in wild-type as compared with Pept2 null mice (P<0.01). Uptake of GlySar by the ependymal-subependymal layer and septal region was higher in wild-type than in null mice, but the half-distance of penetration into parenchyma was significantly less in wild-type mice. The latter is probably because of the clearance of GlySar from interstitial fluid by brain cells expressing PEPT2, which stops further penetration. These studies show that PEPT2 knockout can significantly modify the spatial distribution of GlySar and cefadroxil (and presumably other peptides/mimetics and peptide-like drugs) in brain.

Indexed as

AnimalsAnti-Bacterial AgentsAutoradiographyBrainCefadroxilChoroid PlexusDipeptidesHalf-LifeImage Processing, Computer-AssistedInjections, IntraventricularMannitolMiceMice, Inbred C57BLMice, KnockoutSymportersAnti-Bacterial AgentsCefadroxilDipeptidesglycylsarcosinehydrogen-coupled oligopeptide transporter PepT2MannitolSymporters

Identifiers

PMID20571525
PMCPMC2965812
OpenAlexW2045827440

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.