Biophysical Studies of Non-Invasive Brain Cell Stimulation with Focused Ultrasound

聚焦超声非侵入性脑细胞刺激的生物物理研究

基本信息

批准号：
9448055
负责人：
Jerome Jacques Lacroix
金额：
$ 17.58万
依托单位：
WESTERN UNIVERSITY OF HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-25 至 2019-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9448055
关键词：
Acoustic Stimulation Acoustics Acute Address Adverse effects Area Astrocytes Biological Biophysical Process Biophysics Brain Brain region Calcium Calcium Channel Calcium Signaling Cell membrane Cell physiology Cells Clinic Cyclic AMP-Dependent Protein Kinases Cytoskeletal Proteins Data Dementia Disease Energy Transfer Engineering Extracellular Matrix Female Fluorescence Focused Ultrasound Genetic Engineering Goals Green Fluorescent Proteins Human Image Intervention Ion Channel Lead Legal patent Lipid Bilayers Longevity Measurement Measures Mechanical Stimulation Mechanical Stress Mechanics Mediating Membrane Membrane Proteins Memory Metabolic Modality Modeling Molecular Molecular Conformation Mus Nanotechnology Nerve Regeneration Neuroglia Neurologic Neurology Neurons Operative Surgical Procedures Optical reporter Optics Osmotic Shocks Patients Pharmacology Physiologic pulse Positioning Attribute Proteins Reporter Reporting Resolution Rodent Sampling Signal Transduction Slice Stimulus Stretching System Techniques Technology Technology Transfer Testing Therapeutic Time Tissues Traumatic Brain Injury Ultrasonography Variant Work base biophysical analysis brain cell brain size brain tissue clinical translation design engineering design experimental study inhibitor/antagonist innovation magnetic field male mechanical force neural circuit neuroregulation neurovascular neurovascular coupling new technology optical sensor relating to nervous system response sensor voltage

项目摘要

Abstract Low-intensity pulsed ultrasound stimulation (LIPUS) is a promising technology for non-invasive deep brain neuromodulation. Unfortunately, this technology is presently not available in the clinic due to the lack of understanding of the molecular and cellular processes that take place in brain cells upon ultrasound stimulation. The goal of this project is to uncover these mechanism(s). Our preliminary data show that LIPUS elicit robust and consistent calcium signals in astrocytes, suggesting a totally unanticipated mechanism wherein the neuromodulatory effects of LIPUS are mediated by astrocytes, via direct or indirect activation of calcium channels. To investigate these hypotheses, we propose to dissect LIPUS-induced calcium signaling in astrocytes and neurons using pharmacological agents. If successful, this work will help make this new technology available to patients who currently do not have access to effective and safe therapeutic options. Non-invasive astrocyte stimulation with ultrasound may also lead to new treatments for traumatic brain injury, neurovascular diseases or dementia. In parallel to this effort, we will develop genetically-encoded fluorescent reporters of mechanical deformations of plasma membranes induced upon LIPUS. Our preliminary molecular engineering design is very promising and will lead to a patent application upon further characterization and optimization. These sensors will enable rapid and easy localization and quantification of physical perturbations produced in cells and tissues by exogenous and endogenous mechanical forces. We expect these reporters to have a major impact in mechanobiology and nanotechnology.

抽象的低强度脉冲超声刺激（Lipus）是一种无创的有前途的技术深脑神经调节。不幸的是，目前在诊所无法使用这项技术由于缺乏对大脑中发生的分子和细胞过程的了解超声刺激时的细胞。该项目的目的是发现这些机制。我们的初步数据表明，Lipus在星形胶质细胞中引起稳健和一致的钙信号，提出一种完全意外的机制，其中脂肪的神经调节作用是由星形胶质细胞介导，通过钙通道的直接或间接激活。调查这些假设，我们建议在星形胶质细胞和神经元中剖析脂肪诱导的钙信号传导使用药理剂。如果成功，这项工作将有助于使这项新技术目前无法获得有效且安全的治疗选择的患者。超声检查的非侵入性星形胶质细胞刺激也可能导致创伤的新治疗方法脑损伤，神经血管疾病或痴呆症。与这项努力并行，我们将发展质膜机械变形的遗传编码的荧光记者诱导脂肪。我们的初步分子工程设计非常有前途，将会在进一步的表征和优化后导致专利应用。这些传感器会能够快速轻松地定位和量化细胞中产生的物理扰动以及通过外源性和内源性机械力组织。我们希望这些记者能够对机械生物学和纳米技术产生重大影响。