Single-dose ebselen does not afford sustained neuroprotection to rats subjected to severe focal cerebral ischemia

Oxygen free radicals have been involved in the pathophysiology of cerebral ischemia, especially after spontaneous or thrombolytic reperfusion. In this study with rats, we have combined a severe focal ischemic insult (2 h) and a prolonged reperfusion time (7 days) to assess the possible sustained neu...

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Bibliographic Details
Published in:European journal of pharmacology 2004-07, Vol.495 (1), p.55-62
Main Authors: Salom, Juan B, Pérez-Asensio, Fernando J, Burguete, Marı́a C, Marı́n, Nuria, Pitarch, Carlos, Torregrosa, Germán, Romero, Francisco J, Alborch, Enrique
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
Azoles - chemistry
Azoles - metabolism
Azoles - pharmacology
Biological and medical sciences
Body Weight - drug effects
Brain - drug effects
Brain - metabolism
Brain - pathology
Brain Chemistry
Brain Ischemia - etiology
Brain Ischemia - mortality
Brain Ischemia - physiopathology
Cerebral infarct
Drug Administration Schedule
Drug Evaluation, Preclinical - methods
Ebselen
Focal ischemia
Glutathione - chemistry
Glutathione - metabolism
Infarction, Middle Cerebral Artery - etiology
Infarction, Middle Cerebral Artery - physiopathology
Male
Medical sciences
Neurology
Organoselenium Compounds - chemistry
Organoselenium Compounds - metabolism
Organoselenium Compounds - pharmacology
Oxidative stress
Oxidative Stress - drug effects
Rat
Rats
Rats, Wistar
Reactive Oxygen Species - metabolism
Reperfusion
Selenium - metabolism
Spain
Time Factors
Vascular diseases and vascular malformations of the nervous system
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Summary:Oxygen free radicals have been involved in the pathophysiology of cerebral ischemia, especially after spontaneous or thrombolytic reperfusion. In this study with rats, we have combined a severe focal ischemic insult (2 h) and a prolonged reperfusion time (7 days) to assess the possible sustained neuroprotective effect of ebselen (10 or 100 mg/kg), a small, lipophilic organoselenium compound which mimics glutathione peroxidase. Parietal cortical perfusion was measured by laser-Doppler flowmetry, and focal cerebral ischemia was carried out by the intraluminal thread method. We have measured plasma selenium levels, brain reduced glutathione levels, as a marker of oxidative stress, and infarct volume associated with cerebral ischemia. Focal ischemia did not alter reduced glutathione levels, while 60 min reperfusion following ischemia induced a significant ( P
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2004.05.024