PMID:18384965

Citation	Yamagata, K, Ichinose, S, Miyashita, A and Tagami, M (2008) Protective effects of ebselen, a seleno-organic antioxidant on neurodegeneration induced by hypoxia and reperfusion in stroke-prone spontaneously hypertensive rat. Neuroscience 153:428-35
Abstract	Cerebral ischemia followed by oxygen reperfusion induced apoptosis in hippocampal neurons in the stroke-prone spontaneously hypertensive rat (SHRSP) but not in Wistar Kyoto rats (WKY). We investigated whether 2-phenyl-1,2-benzisoselenazol-3(2H)-one, also called PZ51 (ebselen), useful for treating ischemic damage or antihypertension in the brain, can protect against ischemic neuronal damage in SHRSP. In this study, we compared the effects of ebselen, carvedilol, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186) as well as vitamin E, added to cultures of neurons after reoxygenation (20% O(2)) following hypoxia (1% O(2)). SHRSP neurons died rapidly during reoxygenation following hypoxia but were rescued in large measure by 10 muM ebselen (neuronal death; 2.7+/-1.4%). In order of neuroprotective potency, the agents ranked as follows: ebselen>carvedilol>MCI-186>vitamin E. In vivo, strong neuroprotection by ebselen was observed in the hippocampal CA1 region of SHRSP (32.9+/-9.5 apoptotic neuron/1000 neurons, 30 mg/kg/day). Ebselen prevented apoptosis as confirmed by morphological observations in vivo. Its effect was associated with the expression of Bcl-2 and Bax. These findings suggest that ebselen has a marked inhibitory effect on neuronal damage during stroke. Ebselen may be effective in the prevention and/or treatment of neurodegenerative diseases associated with excessive apoptosis in patients with stroke.
Links	PubMed Online version:10.1016/j.neuroscience.2008.02.028
Keywords	Animals; Antioxidants/pharmacology; Azoles/pharmacology; Cell Death/drug effects; Cells, Cultured; DNA, Complementary/biosynthesis; DNA, Complementary/genetics; Dose-Response Relationship, Drug; Hypoxia/complications; Hypoxia/drug therapy; L-Lactate Dehydrogenase/metabolism; Microscopy, Electron; Nerve Degeneration/etiology; Nerve Degeneration/prevention & control; Neurons/drug effects; Neurons/metabolism; Neurons/ultrastructure; Organoselenium Compounds/pharmacology; Proto-Oncogene Proteins c-bcl-2/biosynthesis; RNA/biosynthesis; RNA/genetics; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reperfusion Injury/complications; Reperfusion Injury/drug therapy; Reverse Transcriptase Polymerase Chain Reaction; Stroke/genetics; bcl-2-Associated X Protein/biosynthesis
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:BCL2	involved_in	GO:0014070: response to organic cyclic compound	ECO:0000270: expression pattern evidence used in manual assertion		P		Seeded From UniProt	complete

References

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