Endothelin-1-induced focal cerebral ischemia in the growth hormone/IGF-1 deficient Lewis Dwarf rat.
Endothelin-1-induced focal cerebral ischemia in the growth hormone/IGF-1 deficient Lewis Dwarf rat.
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DOI：
10.1093/gerona/glu118
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发表时间：
2014-11
期刊：
影响因子：
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通讯作者：
Han Yan;M. Mitschelen;Peter Toth;N. Ashpole;J. Farley;Erik L. Hodges;J. Warrington;Song Han
中科院分区：
文献类型：
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作者：
Han Yan;M. Mitschelen;Peter Toth;N. Ashpole;J. Farley;Erik L. Hodges;J. Warrington;Song Han
衰老是脑血管疾病的主要危险因素。生长激素（GH）及其合成代谢介质，胰岛素样生长因子（IGF）-1，随着年龄的增长而减少，这种下降已被证明会促进血管功能障碍。此外，较低的GH/IGF-1水平与人类较高的中风死亡率相关。提示GH/IGF-1水平降低是脑血管病危险性增加的重要因素。本研究旨在评估GH/IGF-1缺乏是否影响脑缺血的结果。我们发现，内皮素-1诱导的大脑中动脉闭塞导致一个温和的，但不显着减少脑梗死面积GH/IGF-1缺陷dw/dw大鼠与对照杂合子同窝和dw/dw大鼠与早期生活GH治疗。内皮素受体的表达和内皮素-1诱导的大脑中动脉收缩在三个实验组中是相似的。有趣的是，dw/dw大鼠表现出减少脑水肿和较少的星形胶质细胞浸润相比，其杂合子同窝仔，这种效果被GH治疗逆转。由于反应性星形胶质细胞对调节卒中后炎症过程、维持血脑屏障和神经修复至关重要，因此需要进一步研究以确定GH/IGF-1缺陷动物脑缺血后星形胶质细胞活化减少的长期功能后果。
Aging is a major risk factor for cerebrovascular disease. Growth hormone (GH) and its anabolic mediator, insulin-like growth factor (IGF)-1, decrease with advancing age and this decline has been shown to promote vascular dysfunction. In addition, lower GH/IGF-1 levels are associated with higher stroke mortality in humans. These results suggest that decreased GH/IGF-1 level is an important factor in increased risk of cerebrovascular diseases. This study was designed to assess whether GH/IGF-1-deficiency influences the outcome of cerebral ischemia. We found that endothelin-1-induced middle cerebral artery occlusion resulted in a modest but nonsignificant decrease in cerebral infarct size in GH/IGF-1 deficient dw/dw rats compared with control heterozygous littermates and dw/dw rats with early-life GH treatment. Expression of endothelin receptors and endothelin-1-induced constriction of the middle cerebral arteries were similar in the three experimental groups. Interestingly, dw/dw rats exhibited reduced brain edema and less astrocytic infiltration compared with their heterozygous littermates and this effect was reversed by GH-treatment. Because reactive astrocytes are critical for the regulation of poststroke inflammatory processes, maintenance of the blood-brain barrier and neural repair, further studies are warranted to determine the long-term functional consequences of decreased astrocytic activation in GH/IGF-1 deficient animals after cerebral ischemia.