![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
INFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA
Inhibition Reduces Secondary Damage in Experimental Spinal Cord Trauma
Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina, Italy (S.C., T.G., E.M., C.C., C.M., R.D.P.); The William Harvey Research Institute, Centre for Experimental Medicine, Nephrology and Critical Care, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London, United Kingdom (M.C., C.T.); Istituto di Ricovero e Cura a Carattere Scientifico Centro Neurolesi "Bonino-Pulejo", Messina, Italy (S.C., E.M., P.B., T.G.); and Department of Experimental Pharmacology, University of Naples "Federico II", Naples, Italy (E.E.)
Glycogen synthase kinase-3 (GSK-3) has recently been identified as an ubiquitous serine-threonine protein kinase that participates in a multitude of cellular processes and plays an important role in the pathophysiology of a number of diseases. The aim of this study was to investigate the effects of GSK-3
inhibition on the degree of experimental spinal cord trauma induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. Spinal cord injury (SCI) in mice resulted in severe trauma characterized by edema, neutrophil infiltration, production of a range of inflammatory mediators, tissue damage, and apoptosis. Treatment of the mice with 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8), a potent and selective GSK-3 inhibitor, significantly reduced the degree of 1) spinal cord inflammation and tissue injury (histological score); 2) neutrophil infiltration (myeloperoxidase activity); 3) inducible nitric-oxide synthase, nitrotyrosine, and cyclooxygenase-2 expression; and 4) and apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and Bax and Bcl-2 expression). In a separate set of experiments, TDZD-8 significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate that treatment with TDZD-8 reduces the development of inflammation and tissue injury associated with spinal cord trauma.
Address correspondence to: Prof. Salvatore Cuzzocrea, 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. E-mail: salvator{at}unime.it
This article has been cited by other articles:
|
|
 |
|
  S. Ceruti, G. Villa, T. Genovese, E. Mazzon, R. Longhi, P. Rosa, P. Bramanti, S. Cuzzocrea, and M. P. Abbracchio The P2Y-like receptor GPR17 as a sensor of damage and a new potential target in spinal cord injury Brain, June 15, 2009; (2009) awp147v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Dill, H. Wang, F. Zhou, and S. Li Inactivation of Glycogen Synthase Kinase 3 Promotes Axonal Growth and Recovery in the CNS J. Neurosci., September 3, 2008; 28(36): 8914 - 8928. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. De Sarno, R. C. Axtell, C. Raman, K. A. Roth, D. R. Alessi, and R. S. Jope Lithium Prevents and Ameliorates Experimental Autoimmune Encephalomyelitis J. Immunol., July 1, 2008; 181(1): 338 - 345. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Guzman, X. Li, C. A. Corbett, R. M. Rossi, T. Bushnell, J. L. Liesveld, J. Hebert, F. Young, and C. T. Jordan Rapid and selective death of leukemia stem and progenitor cells induced by the compound 4-benzyl, 2-methyl, 1,2,4-thiadiazolidine, 3,5 dione (TDZD-8) Blood, December 15, 2007; 110(13): 4436 - 4444. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
