Limb remote ischemic post‑conditioning reduces injury and improves long‑term behavioral recovery in rats following subarachnoid hemorrhage: Possible involvement of the autophagic process.

Limb remote ischemic post‑conditioning reduces injury and improves long‑term behavioral recovery in rats following subarachnoid hemorrhage: Possible involvement of the autophagic process.
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肢体远程缺血后处理可减少蛛网膜下腔出血后大鼠的损伤并改善长期行为恢复:可能涉及自噬过程

DOI:
10.3892/mmr.2017.7858
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发表时间:
2018-01
影响因子:
3.4
通讯作者:
Miao YF
Miao YF
中科院分区:
医学4区
文献类型:
--
作者:
Hu X;Lv T;Yang SF;Zhang XH;Miao YF

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出血相关的神经损伤是蛛网膜下腔出血(SAH)后致残和致死的主要原因。本研究旨在利用血管内穿刺大鼠SAH模型,探讨肢体远程缺血后处理(RIPostC)潜在的神经保护作用以及自噬可能发挥的作用。使用动脉瘤夹在双侧股动脉进行3个周期的阻断(10分钟)和再通(10分钟)来诱导RIPostC。早期RIPostC在SAH后立即开始,延迟RIPostC在延迟30分钟后开始,重复RIPostC组每天进行该操作,持续3天。术后3天进行脑含水量、SAH分级、脱氧核糖核苷酸末端转移酶介导的dUTP缺口末端标记 - DAPI染色、透射电子显微镜检查以及神经和行为学测试。1个月后使用转棒试验和莫里斯水迷宫试验评估行为和记忆的长期结果。使用蛋白质印迹法评估自噬的生物标志物,包括Beclin - 1和微管相关蛋白1轻链3(LC3)。本研究结果表明,与其他组相比,重复RIPostC能够减轻脑水肿,防止神经元凋亡,并改善短期和长期的神经功能及记忆。重复RIPostC治疗后大脑皮质中的Beclin - 1和LC3表达上调。自噬溶酶体在SAH后3天增加,并在重复RIPostC组中维持1个月。因此,本研究表明,优化的重复RIPostC可能提供一种非侵入性策略来诱导神经保护,并改善SAH相关脑损伤的短期和长期预后,可能涉及自噬途径。
Hemorrhage-related neurologic injury is a primary cause of disability and mortality following subarachnoid hemorrhage (SAH). The aim of the present study was to investigate the potential neuroprotective effect and the possible role of autophagy in limb remote ischemic post-conditioning (RIPostC) using an endovascular puncture rat model of SAH. RIPostC was induced by three cycles of occlusion (10 min) and release (10 min) in the bilateral femoral artery using an aneurysm clip. Early RIPostC began immediately following SAH, delayed RIPostC began following a 30 min delay and the repeated RIPostC group underwent the protocol every day for 3 days. Brain water content, SAH grading, terminal deoxynucleotidyl transferase dUTP nick end labeling-DAPI staining, transmission electron microscopy, and neurological and behavioral tests were conducted three days following surgery. Long term outcomes of behavior and memory were assessed using a rotarod test and Morris water maze test 1 month subsequently. Biomarkers of autophagy, including Beclin-1 and light chain 3 (LC3), were assessed using western blotting. The results of the present study demonstrated that, compared with other groups, repeated RIPostC was able to alleviate brain edema, prevent neuronal apoptosis, and improve short term and long term neurological function and memory. Beclin-1 and LC3 in the cortex were upregulated following treatment with repeated RIPostC. Autolysosomes increased 3 days following SAH and were maintained for 1 month in the repeated RIPostC group. Therefore, the present study indicated that the optimized repeated RIPostC may provide a noninvasive strategy to induce neuroprotection, and improve the short and long term outcomes of SAH-related cerebral injury, possibly involving the autophagy pathway.
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发表时间: 2015-10-01
期刊: CANCER LETTERS
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