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正电子发射断层扫描术(PET)对神经干细胞和 GABA 前体细胞移植后颞叶癫痫大鼠模型代谢变化的研究

PET imaging of metabolic changes after neural stem cells and GABA progenitor cells transplantation in a rat model of temporal lobe epilepsy.

机构信息

Department of Nuclear Medicine and PET Center, The Second Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.

Institute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, China.

出版信息

Eur J Nucl Med Mol Imaging. 2019 Oct;46(11):2392-2397. doi: 10.1007/s00259-019-04408-2. Epub 2019 Jul 24.

Abstract

PURPOSE

Stem cell transplantation is promising for temporal lobe epilepsy (TLE) treatment. This study aimed to use PET imaging for the investigation of dynamic metabolic changes after transplantation of human neural stem cells (NSCs) and human GABA progenitor cells (GPCs) in a rat model of TLE.

METHODS

F-FDG PET imaging, video-electroencephalography (EEG), whole-cell patch-clamp recordings and immunostaining were performed after transplantation of NSCs and GPCs.

RESULTS

PET imaging demonstrated that glucose metabolism was gradually improved in the NSCs group, but decreased in GPCs and the control. Video-EEG manifested that seizures were suppressed after NSCs or GPCs transplantation; whole-cell patch-clamp confirmed increased inhibitory response of GPC-derived cells; immunostaining studies verified that the transplanted NSCs and GPCs could survive, migrate and differentiate into mature neuronal subtypes.

CONCLUSION

F-FDG PET imaging could be a distinguishing approach for evaluation of dynamic glycolytic metabolic changes after transplantation of NSCs and GPCs in TLE. Whole-cell patch-clamp provides evidence for functional maturation and integration of transplanted stem cells within host circuits.

摘要

目的

干细胞移植有望成为颞叶癫痫(TLE)的治疗方法。本研究旨在通过正电子发射断层扫描(PET)成像,研究 TLE 大鼠模型中移植人神经干细胞(NSCs)和人 GABA 祖细胞(GPCs)后,动态代谢变化。

方法

在移植 NSCs 和 GPCs 后,进行 F-FDG PET 成像、视频脑电图(EEG)、全细胞膜片钳记录和免疫染色。

结果

PET 成像显示,NSCs 组的葡萄糖代谢逐渐改善,但 GPCs 组和对照组则降低。视频-EEG 显示,移植 NSCs 或 GPCs 后可抑制癫痫发作;全细胞膜片钳证实,GPC 衍生细胞的抑制反应增加;免疫染色研究证实,移植的 NSCs 和 GPCs 能够存活、迁移并分化为成熟的神经元亚型。

结论

F-FDG PET 成像可以作为评估 TLE 中 NSCs 和 GPCs 移植后动态糖酵解代谢变化的一种区分方法。全细胞膜片钳为移植干细胞在宿主回路中的功能成熟和整合提供了证据。

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