Disorders of the Nervous System
Author: Benjamin Alejandro Zylberberg | email: BZylberberg-iimt@austral.edu.ar
Benjamín A. Zylberberg 1°, Martina Poodts 1°, Julieta Roncoroni 1°, M. Florencia Coronel 1°, Graciela L. Mazzone 1°
1° Instituto de Investigaciones en Medicina Traslacional – CONICET – Universidad Austral, Av. Pte. Perón 1500, B1629AHJ, Pilar, Buenos Aires, Argentina
Excitotoxicity is a major contributor to the pathophysiology of spinal cord injury (SCI), due to the over-activation of glutamate receptors with important consequences for neuronal death, locomotor function loss and neuropathic pain development. We have shown in our previous studies that 1h kainate application (100 µM, KA) induced the endogenous release of glutamate and irreversibly suppressed fictive locomotion. Our objective was to evaluate the neuroprotective effects of resveratrol (RESV, 50 mg/kg), a natural polyphenol, after KA-induced SCI, using in vivo and in vitro models. Locomotor behaviors were evaluated in an open field by applying the Basso Mouse locomotor scale rating (BMS), footprinting and horizontal ladder analysis, 1 or 8 days after KA application. RESV co-application with KA demonstrated a significant increase in the BMS score. The histological analysis confirmed that KA reduced the number neurons, while significant neuroprotection was observed after RESV administration in the ventral, central and dorsal spinal regions. Indeed, the application of RESV significant induced sirtuin 1 and 2 expression, evaluated by immunofluorescence, which was dismissed by co-application of KA. Despite the molecular mechanisms of RESV actions need further clarification, our data suggest that excitotoxic damage may be counteracted by RESV, offering a novel perspective for neuroprotective strategies after SCI. Supported by Universidad Austral and CONICET.