Evidence map›Paper›PMID 28583195›Full record

ArticleJournal of neuroinflammation2017

Effects of phosphodiesterase 3A modulation on murine cerebral microhemorrhages.

Rachita K Sumbria, Vitaly Vasilevko, Mher Mahoney Grigoryan, Annlia Paganini-Hill, Ronald Kim, David H Cribbs, Mark J Fisher

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

Article in Journal of neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.6field-weighted citation impact, top 34% 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

9 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Understanding the Pathophysiology of Cerebral Amyloid Angiopathy.International journal of molecular sciences · 2020
    Review
  8. Article
  9. Article
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

7 authors at 2 institutions in 1 country.

Rachita K SumbriaDepartment of Biopharmaceutical Sciences, School of Pharmacy, Keck Graduate Institute, Claremont, CA, USA.
Vitaly VasilevkoInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
Mher Mahoney GrigoryanDepartment of Neurology, University of California, Irvine, CA, USA.
Annlia Paganini-HillDepartment of Neurology, University of California, Irvine, CA, USA.
Ronald KimDepartment of Pathology & Laboratory Medicine, University of California, Irvine, CA, USA.
David H CribbsInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
Mark J FisherDepartment of Neurology, University of California, Irvine, CA, USA. mfisher@uci.edu.
University of California, Irvine · USKeck Graduate Institute · US

Funding

HEMORHOLOGICAL FACTORS IN CEREBRAL ISCHEMIAR01NS020989 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CRIBBS, DAVID HASTINGS, FISHER, MARK J · 1985 to 2022
$9.1M
NINDS NIH HHS R01 NS020989
6 · The paper itself

Abstract

backgroundCerebral microbleeds (CMB) are MRI-demonstrable cerebral microhemorrhages (CMH) which commonly coexist with ischemic stroke. This creates a challenging therapeutic milieu, and a strategy that simultaneously protects the vessel wall and provides anti-thrombotic activity is an attractive potential approach. Phosphodiesterase 3A (PDE3A) inhibition is known to provide cerebral vessel wall protection combined with anti-thrombotic effects. As an initial step in the development of a therapy that simultaneously treats CMB and ischemic stroke, we hypothesized that inhibition of the PDE3A pathway is protective against CMH development.

methodsThe effect of PDE3A pathway inhibition was studied in the inflammation-induced and cerebral amyloid angiopathy (CAA)-associated mouse models of CMH. The PDE3A pathway was modulated using two approaches: genetic deletion of PDE3A and pharmacological inhibition of PDE3A by cilostazol. The effects of PDE3A pathway modulation on H&E- and Prussian blue (PB)-positive CMH development, BBB function (IgG, claudin-5, and fibrinogen), and neuroinflammation (ICAM-1, Iba-1, and GFAP) were investigated.

resultsRobust development of CMH in the inflammation-induced and CAA-associated spontaneous mouse models was observed. Inflammation-induced CMH were associated with markers of BBB dysfunction and inflammation, and CAA-associated spontaneous CMH were associated primarily with markers of neuroinflammation. Genetic deletion of the PDE3A gene did not alter BBB function, microglial activation, or CMH development, but significantly reduced endothelial and astrocyte activation in the inflammation-induced CMH mouse model. In the CAA-associated CMH mouse model, PDE3A modulation via pharmacological inhibition by cilostazol did not alter BBB function, neuroinflammation, or CMH development.

conclusionsModulation of the PDE3A pathway, either by genetic deletion or pharmacological inhibition, does not alter CMH development in an inflammation-induced or in a CAA-associated mouse model of CMH. The role of microglial activation and BBB injury in CMH development warrants further investigation.

Indexed as

AnimalsCerebral HemorrhageCilostazolCyclic Nucleotide Phosphodiesterases, Type 3Gene DeletionMiceMice, KnockoutMice, TransgenicMicrovesselsPhosphodiesterase 3 InhibitorsTetrazolesTreatment OutcomeCilostazolCyclic Nucleotide Phosphodiesterases, Type 3Pde3a protein, mousePhosphodiesterase 3 InhibitorsTetrazolesCerebral amyloid angiopathyCerebral microbleedsCerebral microhemorrhageCilostazolPhosphodiesterase 3A

Identifiers

PMID28583195
PMCPMC5460510
OpenAlexW2622030771

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.