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预处理神经干细胞增强小鼠缺血再灌注后的神经保护作用。

Adjudin-preconditioned neural stem cells enhance neuroprotection after ischemia reperfusion in mice.

机构信息

School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.

Department of Neurology & Institute of Neurology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Room 211, Med-X Research Institute, 1954 Huashan Road, Shanghai, 200030, China.

出版信息

Stem Cell Res Ther. 2017 Nov 7;8(1):248. doi: 10.1186/s13287-017-0677-0.

DOI:10.1186/s13287-017-0677-0
PMID:29115993
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5678778/
Abstract

BACKGROUND

Transplantation of neural stem cells (NSCs) has been proposed as a promising therapeutic strategy for the treatment of ischemia/reperfusion (I/R)-induced brain injury. However, existing evidence has also challenged this therapy on its limitations, such as the difficulty for stem cells to survive after transplantation due to the unfavorable microenvironment in the ischemic brain. Herein, we have investigated whether preconditioning of NSCs with adjudin, a small molecule compound, could enhance their survivability and further improve the therapeutic effect for NSC-based stroke therapy.

METHOD

We aimed to examine the effect of adjudin pretreatment on NSCs by measuring a panel of parameters after their transplantation into the infarct area of ipsilateral striatum 24 hours after I/R in mice.

RESULTS

We found that pretreatment of NSCs with adjudin could enhance the viability of NSCs after their transplantation into the stroke-induced infarct area. Compared with the untreated NSC group, the adjudin-preconditioned group showed decreased infarct volume and neurobehavioral deficiency through ameliorating blood-brain barrier disruption and promoting the expression and secretion of brain-derived neurotrophic factor. We also employed HO-induced cell death model in vitro and found that adjudin preconditioning could promote NSC survival through inhibition of oxidative stress and activation of Akt signaling pathway.

CONCLUSION

This study showed that adjudin could be used to precondition NSCs to enhance their survivability and improve recovery in the stroke model, unveiling the value of adjudin for stem cell-based stroke therapy.

摘要

背景

神经干细胞（NSCs）移植被提出作为治疗缺血/再灌注（I/R）诱导的脑损伤的一种很有前途的治疗策略。然而，现有的证据也对这种治疗方法提出了挑战，例如由于缺血性脑内的不利微环境，干细胞移植后难以存活。在此，我们研究了用小分子化合物阿朱林预处理 NSCs 是否可以提高它们的存活率，并进一步改善基于 NSCs 的中风治疗的疗效。

方法

我们旨在通过在 I/R 后 24 小时将 NSCs 移植到同侧纹状体梗死区后测量一系列参数来检查阿朱林预处理对 NSCs 的影响。

结果

我们发现，用阿朱林预处理 NSCs 可以增强 NSCs 移植到中风诱导的梗死区后的活力。与未处理的 NSC 组相比，阿朱林预处理组通过改善血脑屏障破坏和促进脑源性神经营养因子的表达和分泌，减少了梗死体积和神经行为缺陷。我们还在体外使用 HO 诱导的细胞死亡模型发现，阿朱林预处理可以通过抑制氧化应激和激活 Akt 信号通路来促进 NSCs 的存活。

结论

这项研究表明，阿朱林可以用于预处理 NSCs 以提高其存活率并改善中风模型中的恢复，揭示了阿朱林在基于干细胞的中风治疗中的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/5678778/3d535e76e73b/13287_2017_677_Fig12_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/5678778/3d535e76e73b/13287_2017_677_Fig12_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/5678778/790ec0bdc0c3/13287_2017_677_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/5678778/d44bd7778c7e/13287_2017_677_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/5678778/2a427b0842dd/13287_2017_677_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/5678778/23e44d507719/13287_2017_677_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/5678778/3c91da0d7429/13287_2017_677_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/5678778/83512973d143/13287_2017_677_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/5678778/3a6065cbcfe9/13287_2017_677_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/5678778/a2d166fee30a/13287_2017_677_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/5678778/84f9179e751d/13287_2017_677_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/5678778/7b5d983da700/13287_2017_677_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/5678778/68b1f27620fb/13287_2017_677_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/5678778/3d535e76e73b/13287_2017_677_Fig12_HTML.jpg

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