PT  - JOURNAL ARTICLE
AU  - Salvatore Cuzzocrea
AU  - Tiziana Genovese
AU  - Emanuela Mazzon
AU  - Concetta Crisafulli
AU  - Rosanna Di Paola
AU  - Carmelo Muià
AU  - Marika Collin
AU  - Emanuela Esposito
AU  - Placido Bramanti
AU  - Christoph Thiemermann
TI  - Glycogen Synthase Kinase-3β Inhibition Reduces Secondary Damage in Experimental Spinal Cord Trauma
AID  - 10.1124/jpet.106.102863
DP  - 2006 Jul 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 79--89
VI  - 318
IP  - 1
4099  - http://jpet.aspetjournals.org/content/318/1/79.short
4100  - http://jpet.aspetjournals.org/content/318/1/79.full
SO  - J Pharmacol Exp Ther2006 Jul 01; 318
AB  - 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-3β 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-3β 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. The American Society for Pharmacology and Experimental Therapeutics