Matrix electrical stimulation regulates CD8+ T cell fate
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ABSTRACT:
PROVIDER: PRJNA1018236 | ENA |
REPOSITORIES: ENA
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Project description:Current standards for safe delivery of electrical stimulation to the central nervous system are based on foundational studies which examined post-mortem tissue for histological signs of damage. This set of observations and the subsequently proposed limits to safe stimulation, termed the “Shannon limits,” allow for a simple calculation (using charge per phase and charge density) to determine the intensity of electrical stimulation that can be delivered safely to brain tissue. In the three decades since the Shannon limits were reported, advances in molecular biology have allowed for more nuanced and detailed approaches to be used to expand current understanding of the physiological effects of stimulation. Here, we investigated spatial transcriptomics as a new approach to assess the safety and efficacy of electrical stimulation in the brain. Electrical stimulation was delivered to the rat visual cortex with either acute or chronic electrode implantation procedures (acute: tissue collection 3 hours post-stimulation on the day of surgery; chronic: stimulation delivered 1-month post-implantation, and tissue collection 24 hours later). To explore the influence of device type and stimulation parameters, we used carbon fiber ultramicroelectrode arrays (7 µm diameter) and microwire electrode arrays (50 µm diameter) delivering charge and charge density levels selected above and below reported tissue damage thresholds (range: 2-20 nC, 0.1-1 mC/cm2). Spatial transcriptomics was performed using Visium Spatial Gene Expression Slides (10x Genomics), which enabled simultaneous immunohistochemistry and spatial transcriptomics to directly compare traditional histological metrics to transcriptional profiles within each tissue sample. Our data revealed unique spatial patterns of differentially expressed genes that are related to cellular processes including inflammation, cell cycle progression, and plasticity. Effects were dependent on stimulation parameters and were localized to both traditional and ultra-small device locations. The abundance of data gathered using this approach allows for sophisticated analysis that can be used to generate new hypotheses while also revealing novel potential biomarkers of neurostimulation.
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Project description:Passive implants currently used in the clinics cannot prevent failure rates and inherent revision arthroplasties. Novel bioelectronic devices that include biophysical stimulators (such as electric stimulators) and sensing systems are desired since these will allow for long-term monitoring and control of the bone-implant interface, in a personalized manner. We have developed acting-sensing dual systems operated at high frequency (HF) that are able to stimulate osteoconduction in pre-osteoblasts and osteoinduction in human adipose-derived mesenchymal stem cells (hASCs). The project included – to our knowledge – the first-time proteomic analysis of microvesicles secreted from osteoblasts electrically-stimulated in vitro by a capacitive stimulator of thin interdigitated electrodes delivering an electrical 60 kHz HF stimulation, 30 min/day. Results revealed regulation of osteodifferentiation and mineralization-related proteins (e.g. Tgfb3, Ttyh3, Itih1, Aldh1a1).
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Project description:Electrical brain stimulation (EBS) has gained popularity for laboratory and clinical applications. However, comprehensive characterization of the cellular diversity and cell type-specific gene expression changes induced by EBS remains limited, particularly with respect to specific brain regions and stimulation sites. In this study, we present the first single-nucleus RNA sequencing (snRNA-seq) profiles of rat cortex, hippocampus, and thalamus subjected to alternating current electrical stimulation (ACES) at 40 Hz.
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Project description:To investigate the mechanism of electrical stimulation in the repair of spinal cord injury, we established a rat model of spinal cord injury. Then, we used RNA-SEQ data obtained from ES treatment and 6 different rat models of spinal cord injury for gene expression profile analysis.
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