Department of Functional Sciences, Center of Clinical and Experimental Medicine, University of Medicine and Pharmacy of Craiova, Craiova 200349, Romania.
Gold Coast Campus, School of Medicine, Griffith University, Southport 4222, Australia.
Int J Mol Sci. 2017 Dec 29;19(1):99. doi: 10.3390/ijms19010099.
The incidence of ischemic stroke in humans increases exponentially above 70 years both in men and women. Comorbidities like diabetes, arterial hypertension or co-morbidity factors such as hypercholesterolemia, obesity and body fat distribution as well as fat-rich diet and physical inactivity are common in elderly persons and are associated with higher risk of stroke, increased mortality and disability. Obesity could represent a state of chronic inflammation that can be prevented to some extent by non-pharmaceutical interventions such as calorie restriction and hypothermia. Indeed, recent results suggest that H₂S-induced hypothermia in aged, overweight rats could have a higher probability of success in treating stroke as compared to other monotherapies, by reducing post-stroke brain inflammation. Likewise, it was recently reported that weight reduction prior to stroke, in aged, overweight rats induced by caloric restriction, led to an early re-gain of weight and a significant improvement in recovery of complex sensorimotor skills, cutaneous sensitivity, or spatial memory.
animal models of stroke done in young animals ignore age-associated comorbidities and may explain, at least in part, the unsuccessful bench-to-bedside translation of neuroprotective strategies for ischemic stroke in aged subjects.
人类的缺血性中风发病率在男性和女性中都随着年龄超过 70 岁而呈指数级增长。糖尿病、动脉高血压或合并症因素如高胆固醇血症、肥胖和体脂分布以及高脂肪饮食和缺乏身体活动等在老年人中很常见,与更高的中风风险、更高的死亡率和残疾率相关。肥胖可能代表一种慢性炎症状态,这种状态在一定程度上可以通过非药物干预来预防,如热量限制和低温。事实上,最近的结果表明,与其他单疗法相比,H₂S 诱导的老年超重大鼠低温可能更有可能成功治疗中风,因为它可以减少中风后的脑炎症。同样,最近有报道称,在超重的老年大鼠中,通过热量限制进行的中风前减肥导致体重的早期恢复,并显著改善复杂感觉运动技能、皮肤敏感性或空间记忆的恢复。
在年轻动物中进行的中风动物模型忽略了与年龄相关的合并症,这至少可以部分解释为什么用于缺血性中风的神经保护策略在老年患者中从实验室到临床的转化不成功。