Neuroprotective effects of poly (ADP-ribose) polymerase inhibitors in transient focal cerebral ischemia of rats.
OBJECTIVE
To explore the role of poly (ADP-ribose) polymerase (PARP) in focal cerebral ischemia with reperfusion injury.


METHODS
Male Wistar rats underwent 3.5-h of temporary middle cerebral artery occlusion by intraluminal suture. Infarction volume was showed with 2,3,5-triphenyltetrazolium chloride (TTC) staining and quantitated by image analysis system, neurologic scores were determined with a 0-5 grading scale.


RESULTS
3-Aminobenzamide (3-AB) 10 mg.kg-1 or nicotinamide (Nic) at 20 mg.kg-1 showed potent neuroprotective effects within 0-6 h, neurologic deficits were attenuated. With the increasing dose of PARP inhibitors, beneficial effects were compromised, particularly, administration of Nic 60 mg.kg-1 at the onset of reperfusion drastically accelerated brain damage. Phytomenadione, a selective inhibitor of mono (ADP-ribosyl) transferase, had little effect on infarction volume.


CONCLUSIONS
Transient incomplete inhibition of PARP provides a neuroprotective effects against cerebral ischemia-reperfusion injury, with a relatively wide therapeutic window, whereas severe inhibition of this enzyme, especially in reperfusion phase, is detrimental.
Sun
A Y
AY
National Laboratory of Medical Neurobiology, Shanghai Medical University, China.
Cheng
J S
JS
D036002:ADP Ribose Transferases / Q000037:antagonists & inhibitors; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage*; D001921:Brain / Q000473:pathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D002546:Ischemic Attack, Transient / Q000150:complications / Q000473:pathology*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D009536:Niacinamide / Q000008:administration & dosage; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000473:pathology; D010837:Vitamin K 1 / Q000494:pharmacology
D001549:Benzamides; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009536:Niacinamide; D010837:Vitamin K 1; C025160:3-aminobenzamide; D036002:ADP Ribose Transferases