A Y Sun1, J S Cheng. 1. National Laboratory of Medical Neurobiology, Shanghai Medical University, China.
Abstract
AIM: 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. CONCLUSION: 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.
AIM: 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. CONCLUSION: 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.
Authors: A S Mandir; M F Poitras; A R Berliner; W J Herring; D B Guastella; A Feldman; G G Poirier; Z Q Wang; T M Dawson; V L Dawson Journal: J Neurosci Date: 2000-11-01 Impact factor: 6.167
Authors: Juan D Unciti-Broceta; José Maceira; Sonia Morales; Angélica García-Pérez; Manuel E Muñóz-Torres; Jose A Garcia-Salcedo Journal: J Biol Chem Date: 2013-02-26 Impact factor: 5.157