Studies of locomotor network neuroprotection by the selective poly(ADP-ribose) polymerase-1 inhibitor PJ-34 against excitotoxic injury to the rat spinal cord in vitro

elayed neuronal destruction after acute spinal injury is attributed to excitotoxicity mediated by hyperactivation of poly(ADP-ribose) polymerase-1 (PARP-1) that induces 'parthanatos', namely a non-apoptotic cell death mechanism. With an in vitro model of excitotoxicity, we have previously observed parthanatos of rat spinal cord locomotor networks to be decreased by a broad spectrum PARP-1 inhibitor. The present study investigated whether the selective PARP-1 inhibitor N-(6-oxo-5,6-dihydrophenanthridin-2-yl)(N,N-dimethylamino)acetamide center dot HCl (PJ-34) not only protected networks from kainate-evoked excitotoxicity, but also prevented loss of locomotor patterns recorded as fictive locomotion from lumbar (L) ventral roots (VRs) 24 h later. PJ-34 (60 mu m) blocked PARP-1 activation and preserved dorsal, central and ventral gray matter with maintained reflex activity even after a large dose of kainate.