Evidence map›Paper›PMID 32350344›Full record

ArticleScientific reports2020

Hyperglycemia and advanced glycation end products disrupt BBB and promote occludin and claudin-5 protein secretion on extracellular microvesicles.

Slava Rom, Nathan A Heldt, Sachin Gajghate, Alecia Seliga, Nancy L Reichenbach, Yuri Persidsky

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
6.1field-weighted citation impact, top 3% 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

75 citing papers in PubMed, 140 citations in OpenAlex.

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15 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Slava RomDepartment of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, USA. srom@temple.edu.
Nathan A HeldtDepartment of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, USA.
Sachin GajghateDepartment of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, USA.
Alecia SeligaDepartment of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, USA.
Nancy L ReichenbachDepartment of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, USA.
Yuri PersidskyDepartment of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, USA. yuri.persidsky@tuhs.temple.edu.
Temple University · US

Funding

Blood brain barrier injury in HIV infection complicated by diabetes: Mechanisms and protective strategies preventing cognitive impairmentR01MH115786 · NIMH · TEMPLE UNIV OF THE COMMONWEALTH · PI PERSIDSKY, YURI · 2018 to 2022
$2.5M
PPAR-gamma-mediated neuroprotection against HIV-1 and alcohol CNS injuryR01AA015913 · NIAAA · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI PERSIDSKY, YURI · 2005 to 2009
$1.6M
NIAAA NIH HHS R01 AA015913NIMH NIH HHS R01 MH115786
6 · The paper itself

Abstract

Cognitive impairment is a well-known complication of diabetes mellitus (DM). Microvascular compromise was described one DM complication. Recently we showed blood brain barrier (BBB) permeability and memory loss are associated with diminution of tight junctions (TJ) in brain endothelium and pericyte coverage and inflammation in cerebral microvessels and brain tissue paralleling hyperglycemia in mice of both DM types. The current study demonstrates that exposure of brain microvessels to hyperglycemic conditions or advanced glycation end products (AGEs) ex vivo resulted in significant abnormalities in membranous distribution of TJ proteins. We found significant increase in the amount of extracellular vesicles (EVs) isolated from DM mice and enhanced presence of TJ proteins, occludin and claudin-5, on EVs. Exposure of BMVECs to high glucose and AGEs led to significant augmentation of ICAM and VCAM expression, elevated leukocyte adhesion to and migration across BMVEC monolayers, and increased BBB permeability in vitro. Pericytes exposed to hyperglycemia and AGEs displayed diminished expression of integrin α1, PDGF-R1β and connexin-43. Our findings indicate BBB compromise in DM ex vivo, in vitro and in vivo models in association with BMVEC/pericyte dysfunction and inflammation. Prevention of BBB injury may be a new therapeutic approach to avert cognitive demise in DM.

Indexed as

AnimalsBlood-Brain BarrierClaudin-5Extracellular VesiclesGene Expression RegulationGlycation End Products, AdvancedHyperglycemiaMaleMiceOccludinPericytesClaudin-5Cldn5 protein, mouseGlycation End Products, AdvancedOccludinOcln protein, mouse

Identifiers

PMID32350344
PMCPMC7190636
OpenAlexW3022409645

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.