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Inhibition of tyrosine kinase-mediated cellular signalling by Tyrphostins AG126 and AG556 modulates secondary damage in experimental spinal cord trauma.
Neuropharmacology. 2007 Jun; 52(7):1454-71.N

Abstract

Protein tyrosine kinases help to regulate the expression of many genes, which play an important role in the pathophysiology of a number of diseases. Here we investigate the effects of the tyrosine kinase inhibitors, AG126 and AG556 on the degree of experimental spinal cord trauma induced by the application of vascular clips to the dura via a four-level T4-T8 laminectomy. Spinal cord injury in mice resulted in severe trauma characterized by oedema, neutrophil infiltration, production of a range of inflammatory mediators, tissue damage, and apoptosis. Treatment of the mice with AG126 and AG556 significantly reduced the degree of (1) spinal cord inflammation and tissue injury (histological score), (2) neutrophil infiltration (myeloperoxidase activity), (3) iNOS, nitrotyrosine, and PARP expression and (4) apoptosis (TUNEL staining and Bax and Bcl-2 expression). In a separate set of experiments, AG126 and AG556 significantly ameliorated the recovery of limb function (evaluated by motor recovery score). This study provides an experimental evidence that (1) prevention of the activation of protein tyrosine kinases reduces the development of inflammation and tissue injury associated with spinal cord trauma, and (2) inhibition of the activity of certain tyrosine kinases may represent a novel approach for the therapy of spinal cord trauma.

Authors+Show Affiliations

Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, 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
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17418876

Citation

Genovese, Tiziana, et al. "Inhibition of Tyrosine Kinase-mediated Cellular Signalling By Tyrphostins AG126 and AG556 Modulates Secondary Damage in Experimental Spinal Cord Trauma." Neuropharmacology, vol. 52, no. 7, 2007, pp. 1454-71.
Genovese T, Mazzon E, Esposito E, et al. Inhibition of tyrosine kinase-mediated cellular signalling by Tyrphostins AG126 and AG556 modulates secondary damage in experimental spinal cord trauma. Neuropharmacology. 2007;52(7):1454-71.
Genovese, T., Mazzon, E., Esposito, E., Muià, C., Di Paola, R., Crisafulli, C., Bramanti, P., & Cuzzocrea, S. (2007). Inhibition of tyrosine kinase-mediated cellular signalling by Tyrphostins AG126 and AG556 modulates secondary damage in experimental spinal cord trauma. Neuropharmacology, 52(7), 1454-71.
Genovese T, et al. Inhibition of Tyrosine Kinase-mediated Cellular Signalling By Tyrphostins AG126 and AG556 Modulates Secondary Damage in Experimental Spinal Cord Trauma. Neuropharmacology. 2007;52(7):1454-71. PubMed PMID: 17418876.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of tyrosine kinase-mediated cellular signalling by Tyrphostins AG126 and AG556 modulates secondary damage in experimental spinal cord trauma. AU - Genovese,Tiziana, AU - Mazzon,Emanuela, AU - Esposito,Emanuela, AU - Muià,Carmelo, AU - Di Paola,Rosanna, AU - Crisafulli,Concetta, AU - Bramanti,Placido, AU - Cuzzocrea,Salvatore, Y1 - 2007/02/12/ PY - 2006/09/20/received PY - 2007/01/12/revised PY - 2007/01/23/accepted PY - 2007/4/10/pubmed PY - 2007/9/1/medline PY - 2007/4/10/entrez SP - 1454 EP - 71 JF - Neuropharmacology JO - Neuropharmacology VL - 52 IS - 7 N2 - Protein tyrosine kinases help to regulate the expression of many genes, which play an important role in the pathophysiology of a number of diseases. Here we investigate the effects of the tyrosine kinase inhibitors, AG126 and AG556 on the degree of experimental spinal cord trauma induced by the application of vascular clips to the dura via a four-level T4-T8 laminectomy. Spinal cord injury in mice resulted in severe trauma characterized by oedema, neutrophil infiltration, production of a range of inflammatory mediators, tissue damage, and apoptosis. Treatment of the mice with AG126 and AG556 significantly reduced the degree of (1) spinal cord inflammation and tissue injury (histological score), (2) neutrophil infiltration (myeloperoxidase activity), (3) iNOS, nitrotyrosine, and PARP expression and (4) apoptosis (TUNEL staining and Bax and Bcl-2 expression). In a separate set of experiments, AG126 and AG556 significantly ameliorated the recovery of limb function (evaluated by motor recovery score). This study provides an experimental evidence that (1) prevention of the activation of protein tyrosine kinases reduces the development of inflammation and tissue injury associated with spinal cord trauma, and (2) inhibition of the activity of certain tyrosine kinases may represent a novel approach for the therapy of spinal cord trauma. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/17418876/Inhibition_of_tyrosine_kinase_mediated_cellular_signalling_by_Tyrphostins_AG126_and_AG556_modulates_secondary_damage_in_experimental_spinal_cord_trauma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(07)00029-9 DB - PRIME DP - Unbound Medicine ER -