Spinal cord injury (SCI) is a devastating condition often accompanied by motor functional deficits and neuropathic pain. The pharmacological agents used for motor and sensory symptoms treatment after SCI are up to now inadequate. Our previous studies were focused on understanding different stages of the secondary process and SCI key mediators that allow early neuroprotection to be effective. Our objective is to evaluate the role of purinergic signalling to trigger SCI after chemical injury. We have now shown that 1h kainate (100 µM) application largely damages neurons via excitotoxicity (Mazzone et al, 2010). Release of endogenous glutamate and ATP during experimental protocols mimicking SCI in vitro could be reliably monitored on a real-time basis with a commercially available biosensor. Our data indicate a higher glutamate and ATP release induced by kainate. We have also analyzed the effect of Coomassie brilliant blue G (10 mM, BBG), a non-nucleotide purinergic antagonist, to find out the consequences on neurons and glial cells after pharmacological block. Immunohistochemistry indicated a much larger loss of neurons using kainate followed by BBG, without effect on astrocytes. Thus, our data indicate that early release of ATP after excitotoxic damage may affect neuronal survival, with a potential effect on network plasticity and implications for neuroprotective strategies. Supported by ICTP, SISSA, Universidad Austral and CONICET.