Optogenetic Inhibition of Striatal Neuronal Activity Improves the Survival of Transplanted Neural Stem Cells and Neurological Outcomes after Ischemic Stroke in Mice.
Optogenetic Inhibition of Striatal Neuronal Activity Improves the Survival of Transplanted Neural Stem Cells and Neurological Outcomes after Ischemic Stroke in Mice.
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纹状体神经元活动的光遗传学抑制可改善小鼠缺血性中风后移植神经干细胞的存活率和神经系统结果。
DOI：
10.1155/2017/4364302
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发表时间：
2017
影响因子：
4.3
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Lu Y;Jiang L;Li W;Qu M;Song Y;He X;Zhang Z;Yang GY;Wang Y
神经干细胞移植是一种很有前途的改善脑缺血后恢复的治疗方法。然而，植入的NSC的存活、增殖、迁移和分化如何受到内源性神经元活性的影响仍不清楚。在这项工作中，我们使用光遗传学技术来控制纹状体神经元的活性，并研究它们的活性如何影响移植的NSC的存活和迁移以及缺血性卒中后的整体神经学结果。将从表达荧光蛋白的转基因小鼠培养的神经干细胞移植到短暂性大脑中动脉闭塞（tMCAO）手术后的纹状体梗死周围区域。在tMCAO后，通过植入光纤每天兴奋或抑制纹状体神经元15分钟。结果显示，与单独的NSC或PBS组相比，接受NSC移植和光遗传学抑制的小鼠具有较小的脑梗死体积和增加的NSC迁移（p < 0.05）。相比之下，接受NSC移植和光遗传学激发的小鼠与PBS对照组相比，在梗死体积和神经行为改善方面没有差异。体外实验进一步揭示，来自兴奋的GABA能神经元的条件培养基通过旁分泌机制降低NSC的活力。结论纹状体神经元活性的光遗传抑制进一步改善了脑缺血后亚急性期NSC移植后的神经恢复。
Neural stem cell (NSC) transplantation is a promising treatment to improve the recovery after brain ischemia. However, how the survival, proliferation, migration, and differentiation of implanted NSC are influenced by endogenous neuronal activity remains unclear. In this work, we used optogenetic techniques to control the activity of striatal neurons and investigated how their activity affected the survival and migration of transplanted NSCs and overall neurological outcome after ischemic stroke. NSCs cultured from transgenic mice expressing fluorescent protein were transplanted into the peri-infarct region of the striatum after transient middle cerebral artery occlusion (tMCAO) surgery. The striatal neurons were excited or inhibited for 15 minutes daily via implanted optical fiber after tMCAO. The results revealed that mice which received NSC transplantation and optogenetic inhibition had smaller brain infarct volume and increased NSC migration compared to the NSC alone or PBS group (p < 0.05). In contrast, mice which received NSC transplantation and optogenetic excitation showed no difference in infarct volume and neurological behavior improvement compared to the PBS control group. In vitro experiments further revealed that the conditioned media from excited GABAergic neurons reduced NSC viability through paracrine mechanisms. Conclusion. Optogenetic inhibition of striatal neuronal activity further improved neurological recovery after NSC transplantation at the subacute phase after brain ischemia.
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影响因子：
12.4
作者：
Daadi, Marcel M.;Li, Zongjin;Steinberg, Gary K.
通讯作者：
Steinberg, Gary K.
影响因子：
4.4
作者：
Nguyen, Nga;Lee, Sang Bae;Ahn, Jee-Yin
通讯作者：
Ahn, Jee-Yin
DOI：
10.1073/pnas.0404474101
发表时间：
2004-08-10
影响因子：
11.1
作者：
Kelly, S;Bliss, TM;Steinberg, GK
通讯作者：
Steinberg, GK
HMGB1对EPC旁分泌作用的影响促进小鼠缺血后新生血管形成
影响因子：
5.2
作者：
Chen, Chao;Lin, Xiaojie;Yang, Guo-Yuan
通讯作者：
Yang, Guo-Yuan
影响因子：
2.5
作者：
LEWIN, GR;MENDELL, LM
通讯作者：
MENDELL, LM