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.

麦角硫因 (ET) 是一种天然存在的抗氧化剂和细胞保护剂，由真菌和某些细菌合成。最近的研究表明，ET 对神经功能（包括认知和抑郁症动物模型）具有有益作用。本研究的目的是阐明 ET 对啮齿动物中风模型的可能影响。氯化三苯基四唑 (TTC) 测定显示，缺血后脑室内 (icv) 输注 ET 最早可在输注后 1 天显着减少大鼠脑梗塞体积。ET 输注剂量从 50 ng 增加到 200 ng，保护作用呈剂量依赖性增加。这些结果表明 ET 对 CNS 神经元具有保护作用。接下来我们阐明了全身 ET 对中风后小鼠脑梗塞体积的影响。每日ip 注射35 mg/kg ET（第一剂在中风后3小时注射）对梗死体积没有显着影响。然而，每日腹膜内注射70 mg/kg、100 mg/kg、125 mg/kg和150 mg/kg ET，首剂注射时间为3小时后中风，小鼠血管闭塞后 7 天的梗塞体积显着减少。为了阐明在 7 天内的什么时间间隔可以产生有效的保护，在小鼠中进行了第二组实验，使用一种有效的负荷方案，即 125 mg/kg ip ET，但在中风后 1 天、4 天和 7 天进行 MRI 检查。我们发现，早在中风后 1 天，ET 就已经可以预防神经元损伤，并减少脑梗塞的面积。对第三组小鼠（使用 125 mg/kg ip ET）进行的行为实验表明，中风后 1 天，这伴随着某些行为（杆测试）的显着改善。总之，这项研究的结果表明，icv