Deep brain stimulation of the ventromedial prefrontal cortex causes reorganization of neuronal processes and vasculature
Deep brain stimulation of the ventromedial prefrontal cortex causes reorganization of neuronal processes and vasculature
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DOI：
10.1016/j.neuroimage.2015.10.049
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发表时间：
2016-01-15
期刊：
影响因子：
5.7
通讯作者：
Lerch, Jason P.
中科院分区：
文献类型：
--
作者：
Chakravarty, M. Mallar;Hamani, Clement;Lerch, Jason P.
背景：胼胝体下扣带区慢性高频电深部脑刺激（DBS）目前正在临床研究作为难治性抑郁症的治疗方法。在啮齿类动物模型中，同源区域腹内侧前额叶皮层 (VMPFC) 的实验性 DBS 先前已证明具有抗抑郁样作用。我们的目标是确定结构重塑是否伴随着之前观察到的慢性 DBS 导致的脑功能改变。方法：在这里，我们每天对 8 只 9 周龄的 C57Bl/6 小鼠应用 6 小时高频双侧 VMPFC DBS，持续 5 天。我们通过使用假刺激组（8只小鼠）和对照组（8只在头骨上钻了一个孔的小鼠）研究了“微损伤”效应。死后使用高分辨率磁共振成像对全脑解剖进行研究，并使用组织学和免疫组织化学进一步研究显示体积扩张的区域。结果：与假手术组和对照组相比，DBS 组显示整个海马体和左侧丘脑体积的双侧增加。在体素水平上还观察到局部海马和丘脑体积增加；然而，在 DBS 组和假手术组中都观察到了这些增加。海马体的后续免疫组织化学显示，与对照组相比，DBS 增加了血管大小和突触密度，而假手术组则显示星形胶质细胞大小增加。 结论：我们的工作表明，DBS 不仅通过改变神经回路的功能，而且还通过在细胞水平上改变回路的结构来发挥作用。神经塑性改变可能在影响 DBS 治疗的临床疗效中发挥作用。 (C) 2015 Elsevier Inc. 保留所有权利。
Background: Chronic high-frequency electrical deep brain stimulation (DBS) of the subcallosal cingulate region is currently being investigated clinically as a therapy for treatment of refractory depression. Experimental DBS of the homologous region, the ventromedial prefrontal cortex (VMPFC), in rodent models has previously demonstrated anti-depressant-like effects. Our goal was to determine if structural remodeling accompanies the alterations of brain function previously observed as a result of chronic DBS.Methods: Here we applied 6 h of high-frequency bilateral VMPFC DBS daily to 8 9-week old C57Bl/6 mice for 5 days. We investigated the "micro-lesion" effect by using a sham stimulation group (8 mice) and a control group (8 mice with a hole drilled into the skull only). Whole brain anatomy was investigated post-mortem using high-resolution magnetic resonance imaging and areas demonstrating volumetric expansion were further investigated using histology and immunohistochemistry.Results: The DBS group demonstrated bilateral increases in whole hippocampus and the left thalamus volume compared to both sham and control groups. Local hippocampal and thalamic volume increases were also observed at the voxel-level; however these increases were observed in both DBS and sham groups. Follow-up immunohistochemistry in the hippocampus revealed DBS increased blood vessel size and synaptic density relative to the control group whereas the sham group demonstrated increased astrocyte size.Conclusions: Our work demonstrates that DBS not only works by altering function with neural circuits, but also by structurally altering circuits at the cellular level. Neuroplastic alterations may play a role inmediating the clinical efficacy of DBS therapy. (C) 2015 Elsevier Inc. All rights reserved.