Protective Effect of Ergothioneine Against Stroke in Rodent Models

Ergothioneine (ET) is a naturally occurring antioxidant and cytoprotective agent that is synthesized by fungi and certain bacteria. Recent studies have shown a beneficial effect of ET on neurological functions, including cognition and animal models of depression. The aim of this study is to elucidate a possible effect of ET in rodent models of stroke. Post-ischemic intracerebroventricular (i.c.v.) infusion of ET significantly reduced brain infarct volume by as early as 1 day after infusion in rats, as shown by triphenyltetrazolium chloride (TTC) assay. There was a dose-dependent increase in protection, from 50 to 200 ng of ET infusion. These results suggest that ET could have a protective effect on CNS neurons. We next elucidated the effect of systemic ET on brain infarct volume in mice after stroke. Daily i.p. injection of 35 mg/kg ET (the first dose being administered 3 h after stroke) had no significant effect on infarct volume. However, daily i.p. injections of 70 mg/kg, 100 mg/kg, 125 mg/kg and 150 mg/kg ET, with the first dose administered 3 h after stroke, significantly decreased infarct volume at 7 days after vessel occlusion in mice. In order to elucidate at what time interval during the 7 days there could be effective protection, a second set of experiments was carried out in mice, using one of the effective loading protocols, i.e. 125 mg/kg i.p. ET but the brains were analyzed at 1, 4 and 7 days post-stroke by MRI. We found that ET was already protective against neuronal injury and decreased the size of the brain infarct from as early as 1 day post-stroke. Behavioral experiments carried out on a third set of mice (using 125 mg/kg i.p. ET) showed that this was accompanied by significant improvements in certain behaviors (pole test) at 1 day after stroke. Together, results of this study indicate that i.c.v. and systemic ET are effective in reducing brain infarct volume after stroke in rodent models.