Growth differentiation factor-11 supplementation improves survival and promotes recovery after ischemic stroke in aged mice
Growth differentiation factor-11 supplementation improves survival and promotes recovery after ischemic stroke in aged mice
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DOI：
10.18632/aging.103122
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发表时间：
2020-05-15
期刊：
影响因子：
5.2
通讯作者：
Chauhan, Anjali
中科院分区：
文献类型：
--
作者：
Hudobenko, Jacob;Ganesh, Bhanu Priya;Chauhan, Anjali
生长分化因子（GDF）11水平随年龄增长而下降。与年龄相关的GDF 11丢失与多种年龄相关疾病的发病机制有关。补充GDF 11可逆转老年小鼠的心脏肥大、骨丢失和肺功能障碍，表明GDF 11具有恢复活力的作用。关于GDF 11在老年小鼠急性损伤（如中风）后改善恢复的潜力，人们知之甚少。在年轻和老年雄性小鼠和死后人脑样品中评估GDF 11/8水平。使老年小鼠经历短暂的大脑中动脉闭塞（MCAo）。MCAo后5天，小鼠接受溴脱氧尿苷/ 5-溴-2 '-脱氧尿苷（BrdU）和重组GDF 11或载体5天，并评估中风后1个月的恢复情况。MRI用于确定脑卒中后30天的脑脊液（CSF）体积、胼胝体（CC）面积和脑萎缩。免疫组织化学用于评估胶质增生、神经发生、血管生成和突触密度。随着年龄的增长，在小鼠和人类中发现较低的GDF 11/8水平（p
Growth differentiation factor (GDF) 11 levels decline with aging. The age-related loss of GDF 11 has been implicated in the pathogenesis of a variety of age-related diseases. GDF11 supplementation reversed cardiac hypertrophy, bone loss, and pulmonary dysfunction in old mice, suggesting that GDF11 has a rejuvenating effect. Less is known about the potential of GDF11 to improve recovery after an acute injury, such as stroke, in aged mice. GDF11/8 levels were assessed in young and aged male mice and in postmortem human brain samples. Aged mice were subjected to a transient middle cerebral artery occlusion (MCAo). Five days after MCAo, mice received and bromodeoxyuridine / 5-Bromo-2'-deoxyuridine (BrdU) and either recombinant GDF11 or vehicle for five days and were assessed for recovery for one month following stroke. MRI was used to determine cerebrospinal fluid (CSF) volume, corpus callosum (CC) area, and brain atrophy at 30 days post-stroke. Immunohistochemistry was used to assess gliosis, neurogenesis, angiogenesis and synaptic density. Lower GDF11/8 levels were found with age in both mice and humans (p