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.