Neuroprotection against nitric oxide injury with inhibitors of ADP-ribosylation.
We investigated the effect of nitric oxide (NO) upon CA1 neurons of the hippocampal slice. NO was given via perfusate without oxygen and with glucose concentration increased to 10 mM to prevent hypoxic injury. Exposure to NO for 10 min produced severe neuronal injury, with CA1 orthodromic 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 recovering to 116 +/- 10% orthodromically, and 96 +/- 4% antidromically. Protection was also seen with 3'-aminobenzamide, another poly-ADP-ribosylation inhibitor, suggesting that poly-ADP-ribosylation may play an important role in NO-mediated neuronal injury.
Wallis
R A
RA
Sepulveda VAMC, CA 91343.
Panizzon
K L
KL
Henry
D
D
Wasterlain
C G
CG
D000246:Adenosine Diphosphate Ribose / Q000037:antagonists & inhibitors*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D066298:In Vitro Techniques; D008297:Male; D009422:Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects; D009536:Niacinamide / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects
D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D000246:Adenosine Diphosphate Ribose; D009536:Niacinamide; D009569:Nitric Oxide; C025160:3-aminobenzamide