NEUROPROTECTIVE EFFECTS OF POLY (ADP-RIBOSE) POLYMERASE INHIBITORS INTRANSIENT FOCAL CEREBRAL-ISCHEMIA OF RATS

AIM: To explore the role of poly (ADP-ribose) polymerase (PARP) in foc al cerebral ischemia with reperfusion injury. METHODS: Male Wistar rat s underwent 3.5-h of temporary middle cerebral artery occlusion by int raluminal suture. Infarction volume was showed with 2,3, 5-triphenylte trazolium chloride (TTC) staining and quantitated by image analysis sy stem, neurologic scores were determined with a 0-5 grading scale. RESU LTS: 3-Aminobenzamide (3-AB) 10 mg . kg(-1) or nicotinamide (Nic) at 2 0 mg . kg(-1) showed potent neuroprotective effects within 0-6 h, neur ologic deficits were attenuated. With the increasing dose of PARP inhi bitors, beneficial effect were compromised, particularly, administrati on of Nic 60 mg . kg(-1) at the onset of reperfusion drastically accel erated brain damage. Phytomenadione, a selective inhibitor of mono(ADP -ribosyl) transferase, had little effect on infarction volume. CONCLUS ION: Transient incomplete inhibition of PARP provides a neuroprotectiv e effects against cerebral ischemia-reperfusion injury, with a relativ ely wide therapeutic window, whereas severe inhibition of this enzyme, especially in reperfusion phase, is detrimental.