Evidence map›Paper›PMID 23018453›Full record

ArticleCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology2012

C-reactive protein increases BBB permeability: implications for obesity and neuroinflammation.

Hung Hsuchou, Abba J Kastin, Pramod K Mishra, Weihong Pan

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed, 10 pooled it
4.9field-weighted citation impact, top 4% 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

99 citing papers in PubMed, 10 syntheses or guidelines pooled it, 190 citations in OpenAlex.

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  15. Peripheral and cerebrospinal fluid inflammatory markers in sporadic amyotrophic lateral sclerosis an exploratory cross-sectional association study.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
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39 more citing papers are in PubMed but not listed here.

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

4 authors at 2 institutions in 1 country.

Hung HsuchouBlood-Brain Barrier Group, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
Abba J Kastin
Pramod K Mishra
Weihong Pan
University of Pennsylvania · USPennington Biomedical Research Center · US

Funding

Research BaseP30DK072476 · NIDDK · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · PI Peter Todd Katzmarzyk · 2005 to 2026
$26.5M
Leptin Transport Across the BBB: The Role of ObR (+) AstrocytesR01DK054880 · NIDDK · TULANE UNIVERSITY OF LOUISIANA · PI KASTIN, ABBA J · 1999 to 2014
$4.4M
Neuroimmune modulation across the BBB: Regulation of ILS trafficking by TNFR01NS062291 · NINDS · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · PI PAN, WEIHONG · 2008 to 2012
$1.6M
Consequences of Astrocytic Leptin Receptor Upregulation on ObesityR01DK092245 · NIDDK · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · PI KASTIN, ABBA J · 2011 to 2014
$1.3M
Leptin Transport across the BBB: The Role of ObR (+) astrocytesR56DK054880 · NIDDK · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · PI KASTIN, ABBA J · 2010 to 2010
$222k
NIDDK NIH HHS DK54880NIDDK NIH HHS DK92245NIDDK NIH HHS P30 DK072476NIDDK NIH HHS R01 DK054880NIDDK NIH HHS R01 DK092245NIDDK NIH HHS R56 DK054880NINDS NIH HHS NS62291NINDS NIH HHS R01 NS062291
6 · The paper itself

Abstract

BACKGROUND/

aimsAcute phase C-reactive protein (CRP), elevated in obesity and inflammation, is a major binding protein for leptin. It is thought that CRP contributes to leptin resistance by preventing leptin from crossing the blood-brain barrier (BBB). Here we determined how CRP interacts with the BBB and whether it deters leptin from reaching CNS targets.

methodsBBB permeability, compartmental distribution, tracer stability, and expression of tight junction protein and inflammatory marker were determined.

resultsCRP was stable in blood, but did not permeate the BBB in trace amounts. However, it increased paracellular permeability at a higher dose. Agouti viable (A(vy)) mice with adult-onset obesity show higher CRP entry into the brain. CRP did not permeate hCMEC/D3 cells nor change zona occludin-1 or cyclooxygenase-2 expression. An intermediate dose of CRP had no effect on leptin transport across the BBB after co-treatment. Thus, acute interactions between CRP and leptin at the BBB level were negligible and did not explain the leptin resistance seen in obesity.

conclusionsThe interactions of CRP and the BBB are a two-phase process, with increased paracellular permeability at a high dose that enables its entry into the CNS and serves to induce reactive gliosis and impair CNS function.

Indexed as

Capillary PermeabilityAnimalsBlood-Brain BarrierCentral Nervous SystemC-Reactive ProteinInflammationLeptinMiceMice, Inbred C57BLObesityC-Reactive ProteinLeptin

Identifiers

PMID23018453
PMCPMC4099000
OpenAlexW2087735289

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.