ABSTRACT
Aim To discuss the neuroprotection of an-tioxidant α-phenyl-N-tert-butyl nitrone ( PBN) in Par-kinson's disease ( PD) model. Methods The neuro-protective effects of PBN was explored on 1-methyl-4-phenylpyridinium/1-methyl-4-phenyl-1,2,3,6-tetrahy-dropyridine ( MPP+/MPTP ) induced PD models through a chemical releasing of free radicals in neurons and in vivo. Results PBN significantly scavenged chemical derived free radicals, reduced MPP+induced SH-SY5Y injury and enhanced neurons' viability. In MPTP induced PD model, PBN significantly enhanced the number of tyrosine hydroxylase ( TH)-positive do-pamine ( DA) neurons in the substantia nigra, restored the expression of Nrf2 and HO-1, and raised striatal contents of DA and its metabolites. Conclusion PBN has a potent neuroprotective effect against MPP+/MPTP induced PD models.
ABSTRACT
We sought to know whether a free radical spin trap agent, alpha-phenyl-N-tert-butyl nitrone (PBN) influences brain cell membrane function and energy metabolism during and after transient global hypoxia-ischemia (HI) in the newborn piglets. Cerebral HI was induced by temporary complete occlusion of bilateral common carotid arteries and simultaneous breathing with 8% oxygen for 30 min, followed by release of carotid occlusion and normoxic ventilation for 1 hr (reoxygenationreperfusion, RR). PBN (100 mg/kg) or vehicle was administered intravenously just before the induction of HI or RR. Brain cortex was harvested for the biochemical analyses at the end of HI or RR. The level of conjugated dienes significantly increased and the activity of Na+, K+-ATPase significantly decreased during HI, and they did not recover during RR. The levels of ATP and phosphocreatine (PCr) significantly decreased during HI, and recovered during RR. PBN significantly decreased the level of conjugated dienes both during HI and RR, but did not influence the activity of Na+, K+-ATPase and the levels of ATP and PCr. We demonstrated that PBN effectively reduced brain cell membrane lipid peroxidation, but did not reverse ongoing brain cell membrane dysfunction nor did restore brain cellular energy depletion, in our piglet model of global hypoxic-ischemic brain injury.
Subject(s)
Animals , Adenosine Triphosphate/metabolism , Animals, Newborn , Hypoxia , Brain/drug effects , Cell Membrane/metabolism , Cerebral Cortex , Ischemia , Lipid Peroxidation , Sodium-Potassium-Exchanging ATPase/metabolism , Neuroprotective Agents/pharmacology , Nitrogen Oxides/pharmacology , Phosphocreatine/analogs & derivatives , Reperfusion Injury/drug therapy , Swine , Time FactorsABSTRACT
PURPOSE: We examined the ability of alpha-phenyl-tert-butyl-nitrone (PBN), an electron spin trapper, to determine the neuroprotective effect in the argon laser induced ischemic rat retina model. METHODS: After ischemic condition of rat retina was induced by argon green laser, PBN was given intraperitoneally at 50 or 100 mg/kg and normal saline was injected to control group. After 24 hours, 48 hours, and 7 days, the neuroprotective effect of PBN was examined by electroretinogram (ERG) and after 7 days, the enucleation of eyes was performed and histologic findings were compared by light microscopy and transmission electron microscopy. RESULTS: We found relatively reduced amplitude of ERG wave in the PBN injected group but not so greatly reduced as in normal saline control group. The retinal ganglion cell (RGC) layer and the number of RGCs were affected by acute ischemic changes but in the group of PBN treatment, the cell membrane was well preserved and vecuoles formation, cytoplasmic destructions, nuclear chromatin condensation were reduced. CONCLUSIONS: Systemic administration of PBN can ameliorate an argon laser induced retinal ischemia. Further investigations are necessary to decide effective dose without toxicity and to find more convenient methods of administrations.