Evidence map›Paper›PMID 31104189›Full record

ArticleGeroScience2019

Genetic knockout of myosin light chain kinase (MLCK210) prevents cerebral microhemorrhages and attenuates neuroinflammation in a mouse model of vascular cognitive impairment and dementia.

David J Braun, Adam D Bachstetter, Tiffany L Sudduth, Donna M Wilcock, D Martin Watterson, Linda J Van Eldik

Open access · hybridAbstract read
In one paragraph

Article in GeroScience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

12 citing papers in PubMed, 18 citations in OpenAlex.

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  9. Clinical implication of cellular vaccine in glioma: current advances and future prospects.Journal of experimental & clinical cancer research : CR · 2020
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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 J BraunSanders-Brown Center on Aging, University of Kentucky, 101 Sanders-Brown Bldg., 800 S. Limestone Street, Lexington, KY, 40536, USA.
Adam D BachstetterSanders-Brown Center on Aging, University of Kentucky, 101 Sanders-Brown Bldg., 800 S. Limestone Street, Lexington, KY, 40536, USA.
Tiffany L SudduthSanders-Brown Center on Aging, University of Kentucky, 101 Sanders-Brown Bldg., 800 S. Limestone Street, Lexington, KY, 40536, USA.
Donna M WilcockSanders-Brown Center on Aging, University of Kentucky, 101 Sanders-Brown Bldg., 800 S. Limestone Street, Lexington, KY, 40536, USA.
D Martin WattersonDepartment of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
Linda J Van EldikSanders-Brown Center on Aging, University of Kentucky, 101 Sanders-Brown Bldg., 800 S. Limestone Street, Lexington, KY, 40536, USA. linda.vaneldik@uky.edu.
University of Kentucky · USNorthwestern University · US

Funding

University of Kentucky Alzheimer's Disease Core Center - Biomarker CoreP30AG028383 · NIA · UNIVERSITY OF KENTUCKY · PI NELSON, PETER T. · 2006 to 2020
$23.3M
DRUG DISCOVERY TRAINING IN AGE-RELATED DISORDERST32AG000260 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI WATTERSON, DANIEL MARTIN · 1998 to 2010
$2.7M
Development of Novel p38 MAPK Inhibitors as Therapeutics for CNS DisordersR01AG031311 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI WATTERSON, DANIEL MARTIN · 2008 to 2012
$1.5M
Integrative Chemical Biology of Neurodegeneration: Foundation to Novel TherapiesR01NS056051 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI WATTERSON, DANIEL MARTIN · 2008 to 2011
$1.0M
Vascular-associated neuroinflammation in Alzheimer's disease: differential effects on disease progression modulated by underlying amyloid burdenF32AG058456 · NIA · UNIVERSITY OF KENTUCKY · PI BRAUN, DAVID JAMES · 2017 to 2020
$186k
NIA NIH HHS F32 AG058456NIA NIH HHS P30 AG028383NIA NIH HHS R01 AG031311NIA NIH HHS T32 AG000260NINDS NIH HHS R01 NS056051
6 · The paper itself

Abstract

The blood-brain barrier (BBB) is critical in maintenance of brain homeostasis, and loss of its functional integrity is a key feature across a broad range of neurological insults. This includes both acute injuries such as traumatic brain injury and stroke, as well as more chronic pathologies associated with aging, such as vascular cognitive impairment and dementia (VCID). A specific form of myosin light chain kinase (MLCK210) is a major regulator of barrier integrity in general, including the BBB. Studies have demonstrated the potential of MLCK210 as a therapeutic target for peripheral disorders involving tissue barrier dysfunction, but less is known about its potential as a target for chronic neurologic disorders. We report here that genetic knockout (KO) of MLCK210 protects against cerebral microhemorrhages and neuroinflammation induced by chronic dietary hyperhomocysteinemia. Overall, the results are consistent with an accumulating body of evidence supporting MLCK210 as a potential therapeutic target for tissue barrier dysfunction and specifically implicate it in BBB dysfunction and neuroinflammation in a model of VCID.

Indexed as

Animalsbeta-N-AcetylhexosaminidasesCerebral HemorrhageCognitive DysfunctionDementiaDisease Models, AnimalHyperhomocysteinemiaInterleukin-10Interleukin-1betaInterleukin-6LectinsMice, KnockoutMyosin-Light-Chain KinaseReceptors, Interleukin-1RNA, MessengerTumor Necrosis Factor-alphabeta-N-AcetylhexosaminidasesChil3 protein, mouseInterleukin-10Interleukin-1betaInterleukin-6LectinsMyosin-Light-Chain KinaseReceptors, Interleukin-1RNA, MessengerTumor Necrosis Factor-alphaCerebrovascularKnockoutMicrohemorrhageMyosin light chain kinaseNeuroinflammationVascular cognitive impairment and dementia

Identifiers

PMID31104189
PMCPMC6885026
OpenAlexW2945399296

What OpenQuestion 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 OpenQuestion graph.