NEUROPROTECTION AGAINST NITRIC-OXIDE INJURY WITH INHIBITORS OF ADP-RIBOSYLATION

WE investigated the effect of nitric oxide (NO) upon CA1 neurons of th e hippocampal slice. NO was given via perfusate without oxygen and wit h glucose concentration increased to 10 mM to prevent hypoxic injury. Exposure to NO for 10 min produced severe neuronal injury, with CA1 or thodromic and antidromic population spike regaining only 3 +/- 3% and 9 +/- 3% of initial amplitude after 1 h recovery. Hypoxic controls in contrast, showed orthodromic and antidromic recovery of 98 +/- 5% and 93 +/- 7%. Good protection from NO-induced injury was seen with 10 mM nicotinamide, an inhibitor of poly-ADP-ribosylation, with CA1 PS recov ering to 116 +/- 10% orthodromically, and 96 +/- 4% antidromically. Pr otection was also seen with 3'-aminobenzamide, another poly-ADP-ribosy lation inhibitor, suggesting that poly-ADP-ribosylation may play an im portant role in NO-mediated neuronal injury.