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Intravenous delivery of mesenchymal stem cells protects both white and gray matter in spinal cord ischemia.
Brain Research ( IF 2.7 ) Pub Date : 2020-08-06 , DOI: 10.1016/j.brainres.2020.147040
Naomi Yasuda 1 , Masanori Sasaki 2 , Yuko Kataoka-Sasaki 3 , Hiroshi Nagahama 3 , Jeffery D Kocsis 4 , Nobuyoshi Kawaharada 5 , Osamu Honmou 2
Affiliation  

Ischemic spinal cord injury (iSCI) is a devastating complication of aortic surgery, with few strategies for prevention. Intravenous infusion of mesenchymal stem cells (MSCs) for iSCI has been shown to provide functional improvement through protection of gray matter. The purpose of this study was to investigate additional mechanisms which may exert therapeutic efficacy in iSCI.

Severe iSCI was created to occlude the descending aorta, which was cross-clamped 5 mm distal to the left subclavian artery for 16 min. One day after iSCI induction, iSCI rats were randomized into two groups: one received intravenous infusion of MSCs (MSC-group), the other received vehicle (no cells; vehicle-group). Locomotor function and in vivo MRI were recorded. H&E, Nissl and toluidine blue stainings, immunohistochemical analysis, diffusion tensor imaging (DTI), and the assessment of blood-spinal cord barrier (BSCB) stability were performed.

MSC treated animals exhibited gradual improvement in hind-limb locomotor function during the 4-week study period; however the vehicle-treated group displayed persistent motor deficits. In the MSC-treated group we observed the protection of white and gray matter volume reduction of axonal and neuronal loss or degeneration and preservation of microvasculature including BSCB function.

Intravenous infusion of MSCs may provide therapeutic efficacy to improve functional outcomes in a rat model of severe iSCI via protection of white and gray matter.



中文翻译:

间充质干细胞的静脉内递送保护脊髓缺血中的白质和灰质。

缺血性脊髓损伤 (iSCI) 是主动脉手术的破坏性并发症,几乎没有预防策略。已证明为 iSCI 静脉输注间充质干细胞 (MSC) 可通过保护灰质提供功能改善。本研究的目的是研究可能在 iSCI 中发挥治疗功效的其他机制。

创建严重的 iSCI 以闭塞降主动脉,将其在左锁骨下动脉远端 5 mm 处交叉夹紧 16 分钟。iSCI 诱导后一天,将 iSCI 大鼠随机分为两组:一组接受静脉输注 MSC(MSC 组),另一组接受载体(无细胞;载体组)。记录运动功能和体内MRI。进行了 H&E、尼氏和甲苯胺蓝染色、免疫组织化学分析、扩散张量成像 (DTI) 和血-脊髓屏障 (BSCB) 稳定性评估。

在 4 周的研究期间,MSC 治疗的动物表现出后肢运动功能的逐渐改善;然而,载体治疗组表现出持续的运动缺陷。在 MSC 治疗组中,我们观察到白质和灰质体积减少对轴突和神经元丢失或变性的保护以及微血管系统的保护,包括 BSCB 功能。

MSCs 的静脉输注可能通过保护白质和灰质来改善严重 iSCI 大鼠模型的功能结果。

更新日期:2020-08-11
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