CoChat
Sign Up
Cited by 129Traumatic Brain Injury and Neurovascular DisturbancesProtease and Inhibitor MechanismsBarrier Structure and Function Studies

Downregulation of Matrix Metalloproteinase-9 and Attenuation of Edema via Inhibition of ERK Mitogen Activated Protein Kinase in Traumatic Brain Injury

Mori, Tatsuro, Wang, Xiaoying, Aoki, Toshiaki, Lo, Eng H.·2002·Journal of Neurotrauma
DOI 10.1089/089771502320914642
Open this paper in CoChat — free account

Abstract

Emerging data suggest that matrix metalloproteinase-9 (MMP-9) plays a critical role in the pathophysiology of brain injury. However, the regulatory mechanisms involved in vivo remain unclear. In this study, we focus on a mitogen activated protein kinase (MAPK) pathway that may trigger MMP-9 after traumatic brain injury. We aim to show that inhibition of the extracellular signal regulated kinase (ERK) would attenuate MMP-9 levels, reduce blood-brain barrier damage, and attenuate edema after trauma induced by controlled cortical impact in mouse brain. Western blots showed that phospho-ERK was rapidly upregulated after trauma. Treatment with U0126, which inhibits MEK, the kinase upstream of ERK, effectively prevented the activation of ERK. After trauma, gelatin zymography showed an increase in MMP-9. U0126 significantly reduced trauma-induced MMP-9 levels. Correspondingly, U0126 ameliorated the degradation of the tight junction protein ZO-1, which is an MMP-9 substrate, and significantly attenuated tissue edema. At 7 days after trauma, traumatic lesion volumes were significantly reduced by U0126 compared with saline-treated controls. These data indicate that the ERK MAPK pathway triggers the upregulation in MMP-9 after trauma, and further suggest that targeting the upstream signaling mechanisms that regulate deleterious MMP-9 activity may reveal new therapeutic opportunities for traumatic brain injury.

Integrity signals

Registry

Crossref · 10.1089/089771502320914642

Cites

62 of 62 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Activation of ERK1/2 results in increased ZO-1 degradation during TBI, decreased ZO-1 and claudin 5 in HIV, and reduced occludin and claudin 5 in ischemic stroke.

    “Activation of ERK1/2 results in increased ZO-1 degradation during traumatic brain injury (51), decreased ZO-1 and claudin 5 expression in brain endothelium during HIV infection (52,53), and reduced occludin and claudin 5 expression in BBB endothelium during ischemic stroke (54).”

    From Bacterial induction of Snail1 contributes to blood-brain barrier disruption (2015) · cites this paper as [51]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Mori, T., Wang, X., Aoki, T., & Lo, E. H.
Affiliations
Harvard University (US)
ORCID
Venue
Journal of Neurotrauma
Publisher
SAGE Publications
Published
2002-11
Volume
19
Issue
11
Pages
1411-1419
ISSN
  • 0897-7151 (ISSN-L)
  • 1557-9042
DOI
10.1089/089771502320914642
OpenAlex
W2078262785
Cited by
129
References
62
Citations by year
2026: 3 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 6 · 2020: 2 · 2019: 5 · 2018: 6 · 2017: 7 · 2016: 5 · 2015: 6 · 2014: 3 · 2013: 13 · 2012: 5
FWCI
4.43
Type
journal article
Language
en
Open access
closed
Licence
www.liebertpub.com/nv/resources-tools/text-and-data-mining-policy/121/ (tdm)
Locations
  • Journal of Neurotrauma (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Neurological Disorders and Stroke (R01-NS38731, R01 NS-40529, R01 NS 37074, R01NS040529, R01NS037074, R01NS038731)
Topics
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
MMP-9, MAPK/ERK pathway, traumatic brain injury, cerebral edema, blood-brain barrier disruption, MEK inhibition, U0126, controlled cortical impact
MeSH terms
Animals, Brain Injuries, Butadienes, Edema, Enzyme Inhibitors, Male, Mice, Inbred C57BL, Nitriles, Down-Regulation, Matrix Metalloproteinase 9, Mitogen-Activated Protein Kinases, Mice, Matrix Metalloproteinase Inhibitors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review