Dataset Information

Tissue Response to Deep Brain Stimulation and Microlesion: A Comparative Study.

ABSTRACT: Deep brain stimulation (DBS) is used for a variety of movement disorders, including Parkinson's disease. There are several theories regarding the biology and mechanisms of action of DBS. Previously, we observed an up-regulation of neural progenitor cell proliferation in post-mortem tissue suggesting that DBS can influence cellular plasticity in regions beyond the site of stimulation. We wanted to support these observations and investigate the relationship if any, between DBS, neural progenitor cells, and microglia.We used naïve rats in this study for DBS electrode implantation, stimulation, and microlesions. We used immunohistochemistry techniques for labeling microglial and progenitor cells, and fluorescence microscopy for viewing and quantification of labeled cells.We present data that demonstrates a reciprocal relationship of microglia and neural precursor cells in the presence of acute high frequency stimulation. In our hands, stimulated animals demonstrate significantly lower numbers of activated microglia (p?=?0.026) when compared to microlesion and sham animals. The subthalamic region surrounding the DBS stimulating electrode reveals a significant increase in the number of neural precursor cells expressing cell cycle markers, plasticity and precursor cell markers (Ki67; p?=?0.0013, MCM2; p?=?0.0002).We conclude that in this animal model, acute DBS results in modest local progenitor cell proliferation and influenced the total number of activated microglia. This could be of clinical significance in patients with PD, as it is thought to progress via neuroinflammatory processes involving microglia, cytokines, and the complement system. Further studies are required to comprehend the behavior of microglia in different activation states and their ability to regulate adult neurogenesis under physiologic and pathologic conditions.

SUBMITTER: Vedam-Mai V

PROVIDER: S-EPMC4961567 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Tissue Response to Deep Brain Stimulation and Microlesion: A Comparative Study.

Vedam-Mai Vinata V Baradaran-Shoraka Massoud M Reynolds Brent A BA Okun Michael S MS

Neuromodulation : journal of the International Neuromodulation Society 20160328 5

<h4>Objectives</h4>Deep brain stimulation (DBS) is used for a variety of movement disorders, including Parkinson's disease. There are several theories regarding the biology and mechanisms of action of DBS. Previously, we observed an up-regulation of neural progenitor cell proliferation in post-mortem tissue suggesting that DBS can influence cellular plasticity in regions beyond the site of stimulation. We wanted to support these observations and investigate the relationship if any, between DBS, ...[more]

PMID: 27018335

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Project description:OBJECTIVE:Computational models are a popular tool for predicting the effects of deep brain stimulation (DBS) on neural tissue. One commonly used model, the volume of tissue activated (VTA), is computed using multiple methodologies. We quantified differences in the VTAs generated by five methodologies: the traditional axon model method, the electric field norm, and three activating function based approaches-the activating function at each grid point in the tangential direction (AF-Tan) or in the maximally activating direction (AF-3D), and the maximum activating function along the entire length of a tangential fiber (AF-Max). APPROACH:We computed the VTA using each method across multiple stimulation settings. The resulting volumes were compared for similarity, and the methodologies were analyzed for their differences in behavior. MAIN RESULTS:Activation threshold values for both the electric field norm and the activating function varied with regards to electrode configuration, pulse width, and frequency. All methods produced highly similar volumes for monopolar stimulation. For bipolar electrode configurations, only the maximum activating function along the tangential axon method, AF-Max, produced similar volumes to those produced by the axon model method. Further analysis revealed that both of these methods are biased by their exclusive use of tangential fiber orientations. In contrast, the activating function in the maximally activating direction method, AF-3D, produces a VTA that is free of axon orientation and projection bias. SIGNIFICANCE:Simulating tangentially oriented axons, the standard approach of computing the VTA, is too computationally expensive for widespread implementation and yields results biased by the assumption of tangential fiber orientation. In this work, we show that a computationally efficient method based on the activating function, AF-Max, reliably reproduces the VTAs generated by direct axon modeling. Further, we propose another method, AF-3D as a potentially superior model for representing generic neural tissue activation.

Dataset Information

Tissue Response to Deep Brain Stimulation and Microlesion: A Comparative Study.

Publications

Tissue Response to Deep Brain Stimulation and Microlesion: A Comparative Study.

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