Klinik für Neurologie, Charité-Universitätsmedizin Berlin, Chariteplatz 1, Berlin, Germany 10117.
Stroke. 2011 Nov;42(11):3258-64. doi: 10.1161/STROKEAHA.110.607705. Epub 2011 Sep 15.
Chronic stress is associated with increased stroke risk. However, the underlying pathophysiological mechanisms are poorly understood. We examined the effects of chronic stress on endothelial function and ischemic brain injury in a mouse model.
129/SV mice were treated with glucocorticoid receptor antagonist mifepristone (25 mg kg(-1)/d) or vehicle and exposed to 28 days of chronic stress consisting of exposure to rat, restraint stress, and tail suspension. Heart rate and blood pressure were continuously recorded by telemetry. Endothelial nitric oxide synthase mRNA and protein expression as well as superoxide production and lipid hydroperoxides were quantified. Endothelium-dependent vasorelaxation was measured in aortic rings. Ischemic lesion volume was quantified after 30 minutes filamentous middle cerebral artery occlusion and 72 hours reperfusion.
Chronic stress caused a significant increase in heart rate, impaired endothelium-dependent vasorelaxation, increased superoxide production, and reduced aortic and brain endothelial nitric oxide synthase levels. Animals exposed to chronic stress showed major increases in ischemic lesion size. These deleterious effects of stress were completely reversed by treatment with mifepristone.
Chronic stress increases stroke vulnerability likely through endothelial dysfunction, which can be reversed by a glucocorticoid receptor antagonist.
慢性应激与中风风险增加有关。然而，其潜在的病理生理机制尚不清楚。我们在小鼠模型中研究了慢性应激对血管内皮功能和缺血性脑损伤的影响。
用糖皮质激素受体拮抗剂米非司酮（25mg/kg/d）或载体处理 129/SV 小鼠，并使其暴露于 28 天的慢性应激中，包括暴露于大鼠、束缚应激和悬尾。通过遥测术连续记录心率和血压。定量检测内皮型一氧化氮合酶 mRNA 和蛋白表达以及超氧生成和脂质过氧化物。在主动脉环中测量内皮依赖性血管舒张功能。在 30 分钟的线栓式大脑中动脉闭塞和 72 小时再灌注后，量化缺血性损伤体积。
慢性应激导致心率显著增加，损害了内皮依赖性血管舒张功能，增加了超氧生成，降低了主动脉和脑内皮型一氧化氮合酶水平。暴露于慢性应激的动物缺血性损伤体积明显增大。米非司酮治疗完全逆转了应激的这些有害影响。
慢性应激可能通过血管内皮功能障碍增加中风易感性，而糖皮质激素受体拮抗剂可逆转这种作用。
