Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Pharmacology and Experimental Therapeutics
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleINFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

Evidence for the Role of Mitogen-Activated Protein Kinase Signaling Pathways in the Development of Spinal Cord Injury

Tiziana Genovese, Emanuela Esposito, Emanuela Mazzon, Carmelo Muià, Rosanna Di Paola, Rosaria Meli, Placido Bramanti and Salvatore Cuzzocrea
Journal of Pharmacology and Experimental Therapeutics April 2008, 325 (1) 100-114; DOI: https://doi.org/10.1124/jpet.107.131060
Tiziana Genovese
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Emanuela Esposito
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Emanuela Mazzon
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carmelo Muià
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rosanna Di Paola
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rosaria Meli
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Placido Bramanti
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Salvatore Cuzzocrea
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Mitogen-activated protein kinase (MAPK) signaling pathways involve two closely related MAPKs, known as extracellular signal-regulated kinase (ERK)1 and ERK2. The aim of the present study was to evaluate the contribution of MAPK3/MAPK1 in the secondary damage in experimental spinal cord injury (SCI) in mice. To this purpose, we used 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD98059), which is an inhibitor of MAPK3/MAPK1. Spinal cord trauma was induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. SCI in mice resulted in severe trauma characterized by edema, neutrophil infiltration, and production of inflammatory mediators, tissue damage, and apoptosis. PD98059 treatment (10 mg/kg i.p.) at 1 and 6 h after the SCI significantly reduced 1) the degree of spinal cord inflammation and tissue injury (histological score), 2) neutrophil infiltration (myeloperoxidase activity), 3) nitrotyrosine formation, 4) proinflammatory cytokines expression, 5) nuclear factor-κB activation, 6) phospho-ERK1/2 expression, and 6) apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, Fas ligand, Bax, and Bcl-2 expression). Moreover, PD98059 significantly ameliorated the recovery of limb function (evaluated by motor recovery score) in a dose-dependent manner. Taken together, our results clearly demonstrate that PD98059 treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma.

Footnotes

  • T.G. and E.E. contributed equally to this work.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • doi:10.1124/jpet.107.131060.

  • ABBREVIATIONS: SCI, spinal cord injury; CNS, central nervous system; iNOS, inducible nitric-oxide synthase; ONOO–, peroxynitrite; MAPK, mitogen-activated protein kinase; ERK, extracellular signal-regulated kinase; TNF, tumor necrosis factor; JNK, c-Jun NH2-terminal kinase; IL, interleukin; PD98059, 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; NF-κB, nuclear factor-κB; TUNEL, terminal deoxynucleotidyl transferase dUTP nick-end labeling; U0126, 1,4-diamino-2,3-dicyano-1,4-bis(methylthio)butadiene; MPO, myeloperoxidase activity; FasL, Fas ligand; IκB, inhibitor of nuclear factor-κB; SAPK, stress-activated protein kinase; PMSF, phenylmethylsulfonyl fluoride; p, phosphorylated; MDA, malondialdehyde-bis-(dimethylacetal)1,1,3,3-tetramethoxypropan; BBB, Basso, Beattie, and Bresnahan; IKK, IκB kinase complex; wm, white matter; gm, gray matter.

    • Received August 31, 2007.
    • Accepted January 4, 2008.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 385 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 385, Issue 3
1 Jun 2023
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Evidence for the Role of Mitogen-Activated Protein Kinase Signaling Pathways in the Development of Spinal Cord Injury
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleINFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

Evidence for the Role of Mitogen-Activated Protein Kinase Signaling Pathways in the Development of Spinal Cord Injury

Tiziana Genovese, Emanuela Esposito, Emanuela Mazzon, Carmelo Muià, Rosanna Di Paola, Rosaria Meli, Placido Bramanti and Salvatore Cuzzocrea
Journal of Pharmacology and Experimental Therapeutics April 1, 2008, 325 (1) 100-114; DOI: https://doi.org/10.1124/jpet.107.131060

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleINFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

Evidence for the Role of Mitogen-Activated Protein Kinase Signaling Pathways in the Development of Spinal Cord Injury

Tiziana Genovese, Emanuela Esposito, Emanuela Mazzon, Carmelo Muià, Rosanna Di Paola, Rosaria Meli, Placido Bramanti and Salvatore Cuzzocrea
Journal of Pharmacology and Experimental Therapeutics April 1, 2008, 325 (1) 100-114; DOI: https://doi.org/10.1124/jpet.107.131060
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Population PK/PD analysis of sutimlimab
  • CCR6 selective antagonist in homeostasis and inflammation
  • PK/PD of Dexamethasone in LPS-Challenged Rats
Show more Inflammation, Immunopharmacology, and Asthma

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics