Bone Marrow Mononuclear Cells Transplantation and Training Increased Transplantation of Energy Source Transporters in Chronic Stroke
Bone Marrow Mononuclear Cells Transplantation and Training Increased Transplantation of Energy Source Transporters in Chronic Stroke
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骨髓单核细胞移植和训练增加慢性中风患者能量来源转运蛋白的移植
DOI：
10.1016/j.jstrokecerebrovasdis.2021.105932
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发表时间：
2021
影响因子：
2.5
通讯作者：
Taguchi Akihiko
中科院分区：
文献类型：
--
作者：
Ogawa Yuko;Saino Orie;Okinaka Yuka;Kikuchi-Taura Akie;Takeuchi Yukiko;Taguchi Akihiko
目的：骨髓单个核细胞（BM-MNC）联合训练对脑卒中慢性期有显著的治疗作用。然而，这种联合治疗的机制尚未研究。在这里，我们研究了它对慢性中风mice脑代谢的影响。材料和方法在大脑中动脉闭塞后4周（慢性阶段），静脉内移植BM-MNC（1x 105细胞在100 μL磷酸盐缓冲盐水中）。分别于给药后3 h和10周检测代谢相关基因缺氧诱导因子1-α（Hif-1α）、脯氨酰羟化酶3（Phd 3）、丙酮酸脱氢酶激酶1（Pdk 1）、Na+/K+-ATP酶（Na+/K+-ATP酶）的转录变化（Atp 1 α1 β 3）、连接蛋白、葡萄糖转运蛋白和单羧酸转运蛋白，结果显示BM-MNC移植后3 h对侧皮质代谢相关基因转录激活。在细胞治疗后进行行为测试，并在细胞治疗后10周检查运动功能改善的小鼠的脑代谢。BM-MNC移植和训练的联合治疗的治疗效果是明显的同侧大脑前动脉（ACA）cortex.ConclusionsBM-MNC移植结合训练的转录激活的形式在同侧和对侧的慢性中风激活基因表达。
ObjectivesBone marrow mononuclear cells (BM-MNC) show a significant therapeutic effect in combination with training even in the chronic phase of stroke. However, the mechanism of this combination therapy has not been investigated. Here, we examined its effects on brain metabolism in chronic stroke mice.Materials and methodsBM-MNC (1x105cells in 100 µL of phosphate-buffered saline) were intravenously transplanted at 4 weeks (chronic stage) after the middle cerebral artery occlusion. At 3 h and 10 weeks after the administration of BM-MNC, we evaluated transcription changes of the metabolism-related genes, hypoxia inducible factor 1-α (Hif-1α), prolyl hydroxylase 3 (Phd3), pyruvate dehydrogenase kinase 1 (Pdk1), Na+/K+-ATPase (Atp1α1‒3), connexins, glucose transporters, and monocarboxylate transporters, in the brain during chronic phase of stroke using quantitative polymerase chain reaction.ResultsThe results showed transcriptional activation of the metabolism-related genes in the contralateral cortex at 3 h after BM-MNC transplantation. Behavioral tests were performed after cell therapy, and the brain metabolism of mice with improved motor function was examined at 10 weeks after cell therapy. The therapeutic efficacy of the combination therapy with BM-MNC transplantation and training was evident in the form of transcriptional activation of ipsilateral anterior cerebral artery (ACA) cortex.ConclusionsBM-MNC transplantation combined with training for chronic stroke activated gene expression in both the ipsilateral and the contralateral side.