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体内经非侵入性和靶向递送磁电纳米颗粒实现无线脑刺激。

In Vivo Wireless Brain Stimulation via Non-invasive and Targeted Delivery of Magnetoelectric Nanoparticles.

机构信息

Indiana Spinal Cord and Brain Injury Research Group, Stark Neuroscience Research Institute & Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.

Indiana Spinal Cord and Brain Injury Research Group, Stark Neuroscience Research Institute & Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.

出版信息

Neurotherapeutics. 2021 Jul;18(3):2091-2106. doi: 10.1007/s13311-021-01071-0. Epub 2021 Jun 15.

Abstract

Wireless and precise stimulation of deep brain structures could have important applications to study intact brain circuits and treat neurological disorders. Herein, we report that magnetoelectric nanoparticles (MENs) can be guided to a targeted brain region to stimulate brain activity with a magnetic field. We demonstrated the nanoparticles' capability to reliably evoke fast neuronal responses in cortical slices ex vivo. After fluorescently labeled MENs were intravenously injected and delivered to a targeted brain region by applying a magnetic field gradient, a magnetic field of low intensity (350-450 Oe) applied to the mouse head reliably evoked cortical activities, as revealed by two-photon and mesoscopic imaging of calcium signals and by an increased number of c-Fos expressing cells after stimulation. Neither brain delivery of MENs nor the magnetic stimulation caused significant increases in astrocytes and microglia. Thus, MENs could enable a non-invasive and contactless deep brain stimulation without the need of genetic manipulation.

摘要

无线且精确的深部脑结构刺激在研究完整的脑回路和治疗神经疾病方面具有重要的应用。在此,我们报告称,磁电纳米粒子(MENs)可被引导至靶向脑区,通过磁场刺激脑活动。我们证明了这些纳米粒子能够可靠地在体外皮质切片中引发快速的神经元反应。在静脉注射荧光标记的 MENs 并通过施加磁场梯度将其递送至靶向脑区后,施加于小鼠头部的低强度磁场(350-450 Oe)可靠地诱发了皮质活动,这通过双光子和钙信号的介观成像以及刺激后 c-Fos 表达细胞数量的增加得到证实。MENs 的脑内递送或磁场刺激均不会导致星形胶质细胞和小胶质细胞的显著增加。因此,MENs 可以实现非侵入性和非接触式的深部脑刺激,而无需基因操作。

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