Protective Effect of Ergothioneine Against Stroke in Rodent Models.

Abstract

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 1day after infusion in rats, as shown by triphenyltetrazolium chloride (TTC) assay. There was a dose-dependent increase in protection, from 50 to 200ng 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 35mg/kg ET (the first dose being administered 3h after stroke) had no significant effect on infarct volume. However, daily i.p. injections of 70mg/kg, 100mg/kg, 125mg/kg and 150mg/kg ET, with the first dose administered 3h after stroke, significantly decreased infarct volume at 7days after vessel occlusion in mice. In order to elucidate at what time interval during the 7days there could be effective protection, a second set of experiments was carried out in mice, using one of the effective loading protocols, i.e. 125mg/kg i.p. ET but the brains were analyzed at 1, 4 and 7days 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 1day post-stroke. Behavioral experiments carried out on a third set of mice (using 125mg/kg i.p. ET) showed that this was accompanied by significant improvements in certain behaviors (pole test) at 1day 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.