Tags

Type your tag names separated by a space and hit enter

Evidence for the role of mitogen-activated protein kinase signaling pathways in the development of spinal cord injury.
J Pharmacol Exp Ther. 2008 Apr; 325(1):100-14.JP

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-kappaB 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.

Authors+Show Affiliations

Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Torre Biologica-Policlinico Universitario Via C. Valeria-Gazzi, 98100 Messina, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18180375

Citation

Genovese, Tiziana, et al. "Evidence for the Role of Mitogen-activated Protein Kinase Signaling Pathways in the Development of Spinal Cord Injury." The Journal of Pharmacology and Experimental Therapeutics, vol. 325, no. 1, 2008, pp. 100-14.
Genovese T, Esposito E, Mazzon E, et al. Evidence for the role of mitogen-activated protein kinase signaling pathways in the development of spinal cord injury. J Pharmacol Exp Ther. 2008;325(1):100-14.
Genovese, T., Esposito, E., Mazzon, E., Muià, C., Di Paola, R., Meli, R., Bramanti, P., & Cuzzocrea, S. (2008). Evidence for the role of mitogen-activated protein kinase signaling pathways in the development of spinal cord injury. The Journal of Pharmacology and Experimental Therapeutics, 325(1), 100-14. https://doi.org/10.1124/jpet.107.131060
Genovese T, et al. Evidence for the Role of Mitogen-activated Protein Kinase Signaling Pathways in the Development of Spinal Cord Injury. J Pharmacol Exp Ther. 2008;325(1):100-14. PubMed PMID: 18180375.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence for the role of mitogen-activated protein kinase signaling pathways in the development of spinal cord injury. AU - Genovese,Tiziana, AU - Esposito,Emanuela, AU - Mazzon,Emanuela, AU - Muià,Carmelo, AU - Di Paola,Rosanna, AU - Meli,Rosaria, AU - Bramanti,Placido, AU - Cuzzocrea,Salvatore, Y1 - 2008/01/07/ PY - 2008/1/9/pubmed PY - 2008/4/23/medline PY - 2008/1/9/entrez SP - 100 EP - 14 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 325 IS - 1 N2 - 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-kappaB 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. SN - 1521-0103 UR - https://www.unboundmedicine.com/medline/citation/18180375/Evidence_for_the_role_of_mitogen_activated_protein_kinase_signaling_pathways_in_the_development_of_spinal_cord_injury_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=18180375 DB - PRIME DP - Unbound Medicine ER -