Ebselen in Acute Ischemic Stroke

Abstract

Background and Purpose-The effect of ebselen, a seleno-organic compound with antioxidant activity through a glutathione peroxidase-like action, on the outcome of acute ischemic stroke was evaluated in a multicenter, placebo-controlled, double-blind clinical trial. Methods-Patients diagnosed as having acute ischemic stroke who could receive drug treatment within 48 hours of stroke onset were enrolled. Oral administration of ebselen granules suspended in water (150 mg BID) or placebo was started immediately after admission and was continued for 2 weeks. The major end points were the Glasgow Outcome Scale scores at 1 month and 3 months after the start of treatment. The modified Mathew Scale and modified Barthel Index scores at 1 month and 3 months were also studied as secondary outcome measures. Results-Three hundred two patients were enrolled in the trial. Intent-to-treat analysis of 300 patients (151 given ebselen and 149given placebo) revealed that ebselen treatment achieved a significantly better outcome than placebo at 1 month (Pϭ.023, Wilcoxon rank sum test) but not at 3 months (Pϭ.056, Wilcoxon rank sum test). The improvement was significant in patients who started ebselen within 24 hours of stroke onset but not in those who started treatment after 24 hours. There was a corresponding improvement in the modified Mathew Scale and modified Barthel Index scores. Conclusions-Early treatment with ebselen improved the outcome of acute ischemic stroke. Ebselen may be a promising neuroprotective agent. (Stroke. 1998;29:12-17.)

Selective impairment of hippocampal neurogenesis by chronic alcoholism: Protective effects of an antioxidant

“…Ebselen has been studied as a potential agent to counteract some of the deleterious effects of ethanol. Studies demonstrate that ebselen protects the liver (39), gastric mucosa (37), CNS (40), and peripheral nerves from chronic alcohol exposure (41) by decreasing oxidative stress through inhibition of lipid peroxida- tion. Here, administration of ebselen results in a decrease in ethanol-induced cell death in the DG and particularly in protection of newly born neurons.…”

Ebselen: A substrate for human thioredoxin reductase strongly stimulating its hydroperoxide reductase activity and a superfast thioredoxin oxidant

“…Because ebselen is effective against membrane hydroperoxides, it inhibits both nonenzymatic and enzymatic lipid peroxidation in cells and has anti-inflammatory activity in various animal models (5, 6). Ebselen also will directly inhibit inflammation-related enzymes such as 5-lipoxygenase, nitric oxide synthases, NADPH oxidase, protein kinase C, and ATPase by chemically modifying an SH-group forming a selenosulfide complex (5, 6).Because of its anti-inflammatory properties, ebselen has been used in the treatment of patients with acute ischemic stroke (7,8) or delayed neurological deficits after aneurysmal subarachnoid hemorrhage (9). The results of these clinical trials indicate the benefit of ebselen as a neuroprotective agent.…”

“…Because of its anti-inflammatory properties, ebselen has been used in the treatment of patients with acute ischemic stroke (7,8) or delayed neurological deficits after aneurysmal subarachnoid hemorrhage (9). The results of these clinical trials indicate the benefit of ebselen as a neuroprotective agent.…”

A Novel Antioxidant Mechanism of Ebselen Involving Ebselen Diselenide, a Substrate of Mammalian Thioredoxin and Thioredoxin Reductase

“…In more recent animal model studies, ebselen was shown to reduce oxidative stress in ischemiareperfusion in heart (10) and to have neuroprotective effects in brain (11)(12)(13)(14). More importantly, ebselen has been demonstrated to have beneficial effects in clinical trials for the treatment of patients with delayed neurological deficits after aneurysmal subarachnoid hemorrhage (15) and acute ischemic stroke (16,17).…”