Evidence map›Paper›PMID 33411219›Full record

ReviewMetabolic brain disease2021

Thrombin generation and activity in multiple sclerosis.

Kelley R Jordan, Ivan Parra-Izquierdo, András Gruber, Joseph J Shatzel, Peter Pham, Larry S Sherman, Owen J T McCarty, Norah G Verbout

Open access · greenAbstract readReview
In one paragraph

Review in Metabolic brain disease, 2021. 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
1.8field-weighted citation impact, top 15% 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, 14 citations in OpenAlex.

  1. Observational
  2. Astrocytic ET-1 System Determines Microglia Phenotype Following Spinal Cord Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
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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

8 authors at 3 institutions in 1 country.

Kelley R JordanDepartment of Biomedical Engineering, Oregon Health and Science University, School of Medicine, 3303 SW Bond Avenue, Portland, OR, 97239, USA. Jordake@ohsu.edu.
Ivan Parra-IzquierdoDepartment of Biomedical Engineering, Oregon Health and Science University, School of Medicine, 3303 SW Bond Avenue, Portland, OR, 97239, USA.
András GruberDepartment of Biomedical Engineering, Oregon Health and Science University, School of Medicine, 3303 SW Bond Avenue, Portland, OR, 97239, USA.
Joseph J ShatzelDepartment of Biomedical Engineering, Oregon Health and Science University, School of Medicine, 3303 SW Bond Avenue, Portland, OR, 97239, USA.
Peter PhamDivision of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.
Larry S ShermanDivision of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.
Owen J T McCartyDepartment of Biomedical Engineering, Oregon Health and Science University, School of Medicine, 3303 SW Bond Avenue, Portland, OR, 97239, USA.
Norah G VerboutDepartment of Biomedical Engineering, Oregon Health and Science University, School of Medicine, 3303 SW Bond Avenue, Portland, OR, 97239, USA.
Oregon Health & Science University · USAronora (United States) · USOregon National Primate Research Center · US

Funding

Upgrade of confocal microscopy at the Oregon National Primate Research CenterP51OD011092 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI Bonnie J. Nagel · 2012 to 2026
$203.9M
Characterization of Coagulation Factor-platelet Interactions: Role of FXIR01HL101972 · NHLBI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Owen J McCarty · 2010 to 2026
$8.5M
Therapeutic Protein C Activator for Myocardial IschemiaR44HL117589 · NHLBI · ARONORA, INC. · PI TUCKER, ERIK IAN, VERBOUT, NORAH · 2013 to 2019
$5.2M
Evaluating the Safety and Efficacy of Targeting the Contact Pathway to Prevent Device Associated Thrombosis.R01HL151367 · NHLBI · OREGON HEALTH & SCIENCE UNIVERSITY · PI SHATZEL, JOSEPH JAMES · 2020 to 2024
$1.5M
A non-human primate resource for pre-clinical studies of neurodegenerative diseaseR24NS104161 · NINDS · OREGON HEALTH & SCIENCE UNIVERSITY · PI SHERMAN, LARRY S. · 2018 to 2020
$1.2M
Hyaluron as a regulator of chemotherapy-induced changes in neurogenesisR21CA223461 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI SHERMAN, LARRY S. · 2019 to 2021
$590k
NCI NIH HHS R21 CA223461NHLBI NIH HHS R01 HL101972NHLBI NIH HHS R01 HL151367NHLBI NIH HHS R44 HL117589NIH HHS P51 OD011092NINDS NIH HHS R24 NS104161
6 · The paper itself

Abstract

The coagulation cascade and immune system are intricately linked, highly regulated and respond cooperatively in response to injury and infection. Increasingly, evidence of hyper-coagulation has been associated with autoimmune disorders, including multiple sclerosis (MS). The pathophysiology of MS includes immune cell activation and recruitment to the central nervous system (CNS) where they degrade myelin sheaths, leaving neuronal axons exposed to damaging inflammatory mediators. Breakdown of the blood-brain barrier (BBB) facilitates the entry of peripheral immune cells. Evidence of thrombin activity has been identified within the CNS of MS patients and studies using animal models of experimental autoimmune encephalomyelitis (EAE), suggest increased thrombin generation and activity may play a role in the pathogenesis of MS as well as inhibit remyelination processes. Thrombin is a serine protease capable of cleaving multiple substrates, including protease activated receptors (PARs), fibrinogen, and protein C. Cleavage of all three of these substrates represent pathways through which thrombin activity may exert immuno-regulatory effects and regulate permeability of the BBB during MS and EAE. In this review, we summarize evidence that thrombin activity directly, through PARs, and indirectly, through fibrin formation and activation of protein C influences neuro-immune responses associated with MS and EAE pathology.

Indexed as

AnimalsBlood-Brain BarrierCentral Nervous SystemEncephalomyelitis, Autoimmune, ExperimentalHumansMultiple SclerosisThrombinThrombinActivated protein CExperimental autoimmune encephalomyelitisFibrinMultiple sclerosisThrombin

Identifiers

PMID33411219
PMCPMC7864536
OpenAlexW3120294329

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.