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

Abstract：

: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 < 0.05) decrease in reduced glutathione levels of the ipsilateral hemisphere. Pretreatment with ebselen, which induced significant (P < 0.05) increase in plasma selenium levels, did not significantly alter the decrease in reduced glutathione levels. The ischemic insult induced 30% mortality on average, with deaths always occurring within 12-48 h. Surviving rats suffered up to 25% body weight loss 1 week after the ischemic insult. Infarct volumes were 26.8 +/- 4.7% of the hemisphere in placebo-treated rats, 26.6 +/- 3.6% in 10 mg/kg ebselen-treated rats, and 25.6 +/- 6.4% in 100 mg/kg ebselen-treated rats (not significantly different). Single-dose administration of ebselen does not reduce the size of brain infarct resulting from severe focal cerebral ischemia in rats. In contrast to previous studies with relatively earlier endpoints, we have delayed the measurement of infarct volume to 1 week after the ischemic insult.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Salom JB,Pérez-Asensio FJ,Burguete MC,Marín N,Pitarch C,Torregrosa G,Romero FJ,Alborch E

doi

10.1016/j.ejphar.2004.05.024

keywords:

subject

Has Abstract

pub_date

2004-07-08 00:00:00

pages

55-62

issue

eissn

0014-2999

issn

1879-0712

pii

S0014299904005187

journal_volume

495

pub_type

杂志文章

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