Neutralization of tumor necrosis factor-related apoptosis-inducing ligand reduces spinal cord injury damage in mice.

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
Giuseppina CantarellaRenato Bernardini

Abstract

Spinal cord injury (SCI) is a major cause of disability, its clinical outcome depending mostly on the extent of damage in which proapoptotic cytokines have a crucial function. In particular, the inducers of apoptosis belonging to TNF receptor superfamily and their respective ligands are upregulated after SCI. In this study, the function of the proapoptotic cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in SCI-induced damage was investigated in the mouse. SCI resulted in severe trauma, characterized by prominent inflammation-related damage and apoptosis. Immunostaining for TRAIL and its receptor DR5 was found in the white and gray matter of the perilesional area, as also confirmed by western blotting experiments. Immunoneutralization of TRAIL resulted in improved functional recovery, reduced apoptotic cell number, modulation of molecules involved in the inflammatory response (FasL, TNF-alpha, IL-1beta, and MPO), and the corresponding signaling (caspase-8 and -3 activation, JNK phosphorylation, Bax, and Bcl-2 expression). As glucocorticoid-induced TNF receptor superfamily-related protein (GITR) activated by its ligand (GITRL) contributes to SCI-related inflammation, interactions between TRAIL and GITRL w...Continue Reading

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Citations

Apr 19, 2013·Journal of Molecular Histology·Debao LiZhiming Cui
Nov 30, 2011·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Emanuela EspositoCarlo Riccardi
Jul 6, 2013·Cell Death & Disease·M van DijkE Szegezdi
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Dec 5, 2014·Brain : a Journal of Neurology·Giuseppina CantarellaRenato Bernardini
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Aug 23, 2020·Journal of Cellular and Molecular Medicine·Shiqi GaoAnwen Shao
Apr 19, 2018·Frontiers in Molecular Neuroscience·Daniel Sobrido-Cameán, Antón Barreiro-Iglesias
Aug 15, 2019·Journal of Neuroinflammation·Giulia Di BenedettoGiuseppina Cantarella
Oct 15, 2020·Journal of Neuroinflammation·Chiara BurgalettoGiuseppina Cantarella

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