Effect of Poly (ADP-ribose) Polymerase Inhibitor Against the Ischemia/Reperfusion Injury in Ischemic Stroke Model

BACKGROUND: Nuclear enzyme poly (ADP-ribose) polymerase (PARP) activated by DNA damage participates in DNA repair. However, overactivation of PARP could be an important pathogenic mechanism of ischemic cell death. We investigated the protective effect of an inhibitor of PARP, 3-aminobenzamide (3-AB), against ischemia/reperfusion injury in ischemic stroke model. METHODS: Occlusion of left middle cerebral artery (MCA) was done by intraluminal filament technique in 24 rats weighing from 315 g to 358 g, and reperfusion was done at 2 hours after occlusion. To evaluate the effect of PARP inhibitor in ischemic stroke, 3-AB was administered to 12 rats (3-AB group) 10 minutes before artificial occlusion of left MCA. Infarct area was confirmed by using 2, 3, 5-triphenyltetrazolium chloride stain. The immunoreactivities of poly (ADP-ribose) reflecting activity of enzyme PARP and activated caspase-3 were compared in infarct, peri-infarct and normal zones in 3-AB group and 12 controls. RESULTS: The volume of infarction was decreased about 34% in 3-AB group compared with controls. In 3-AB group, immunoreactivities of PAR were significantly reduced in ischemic regions, especially peri-infarct zone, but those of activated caspase-3 were significantly increased in same region. CONCLUSIONS: These results suggest that treatment of PARP inhibitor can reduce the infarct volume by converting necrotic cell death into apoptosis. PARP inhibition can be another potential neuroprotective strategy in ischemic stroke.

The Effect of Ginseng Saponin on the Dopaminergic Neurons in the Parkinson's Disease Model in Mice

Saponin has been known to be a major antioxidant component in panax ginseng. Recent experimental study suggests that some antioxidant materials prevent Parkinson's disease caused by 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) in an animal model. The present study was performed to demonstrate the effect of ginseng saponins in the Parkinson's disease model induced by MPTP. To verify the effect of ginseng saponin on dopaminergic neurons in the mice brain, the tyrosine hydroxylase-immunoreactive (TH-ir) neurons were observed by immunohistochemical stain and immunoelectron microscopy (preembedding method). Also, in order to estimate the immunoreactivity of dopaminergic neuropils, they were quantified by image analysis. The number of TH-ir neurons of substantia nigra was significantly increased in the high-dose (0.46 mg/kg) ginseng saponin group compared with the MPTP injected group. The immunoreactivity of TH-ir neuropils in striatum was significantly increased in both high and low-dose (0.1 mg/kg) ginseng saponin groups compared with the MPTP injected group. In immunoelectron microscopic observation, TH-ir neurons of the control and both ginseng saponin injected group showed normal nuclei and well preserved cytoplasmic organelles. In the MPTP injected group, dying dopaminergic neurons showed destroyed nuclei and cytoplasmic organelles. These results suggest that ginseng saponin has a protective effect on the Parkinson's disease model induced by MPTP.