CAREER: Magnetic Stimulation and Myelination

脱髓鞘是神经纤维的保护性覆盖物（髓鞘）的降解，这是与神经病症相关的常见副作用，例如，多发性硬化症、阿尔茨海默病和帕金森病。目前治疗脱髓鞘轴突的方法需要重新浸泡和支持少突胶质细胞，这是促进髓鞘发育的特殊细胞。科学界已经发现，当施加外部刺激时，神经元可以被激活，例如电刺激，光遗传刺激和磁刺激。其中，磁刺激是唯一的非侵入性方法，用于再生体内受损的神经元。 该项目旨在发现磁刺激对髓鞘形成过程的影响的新的，基本的理解，最终可能导致创建新的技术和工具，用于开发下一代神经医疗设备。随后，这些设备可能会在未来催生医学界对神经系统疾病的创新治疗。此外，该项目将吸引K-12，本科生和研究生，以激励他们追求再生神经工程的职业生涯。特别是，该项目将采用推广活动和实践活动，积极招募女性，第一代，代表性不足，退伍军人的学生参加该项目，并准备他们为这一令人兴奋的领域作出贡献。PI的首要职业目标是在夏洛特的北卡罗来纳州大学机械工程系生物医学工程和科学中心内建立一个非常成功的神经工程研究和培训计划。 为此，本项目的目标是研究磁刺激（MSTIM）诱导的少突胶质细胞（OLs）轴突髓鞘形成及其信号转导机制。 神经系统中有髓鞘轴突的脱髓鞘是神经系统疾病和脊髓损伤的有害特征。然而，受损的轴突可以被修复（即，当内源性少突胶质细胞祖细胞（OPC）分化成新的髓鞘生成少突胶质细胞（OL）时，然而，由于OPC不能分化OL，内源性OL对轴突的再髓鞘化是有限的。神经元的电活动在OPC分化和轴突的髓鞘化过程中起着必要的作用。神经调节是一种新兴的神经技术，它可以兴奋或抑制功能障碍的神经元回路，使其进入更生理的状态，并可以成为诱导髓鞘形成的有效工具。已经发现神经元的体外电刺激（ESTIM）和光遗传学刺激（OSTIM）增加神经活性并增强轴突的髓鞘形成，但是是侵入性方法。一种类似的技术，磁刺激（MSTIM），是一种非侵入性的神经调节形式，也可以调节神经活动。 本研究计划有三个目标：（1）建立MSTIM神经活性依赖性髓鞘形成的体外模型，（2）研究MSTIM诱导OPCs分化和轴突髓鞘形成，（3）研究MSTIM诱导髓鞘形成的神经元和OPCs释放的神经营养因子和信号分子。该奖项反映了NSF的法定使命，并被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

Demyelination is the degradation of the protective covering (myelin sheath) of nerve fibers, a common side effect associated with neurological disorders, e.g., multiple sclerosis, Alzheimer’s disease and Parkinson’ disease. Current methods to treat demyelinated axons require re-immersion and support of oligodendrocytes, special cells that promote myelin development. The scientific community has found that neurons can be activated when an external stimulation is applied such as Electrical, Optogenetic and Magnetic stimulation. Of these, Magnetic stimulation is the only non-invasive method for regenerating injured neurons in the body. This project seeks to discover a new, fundamental understanding of the effects of Magnetic stimulation on the myelination process that may eventually lead to the creation of new techniques and tools for the development of the next generation of neurological medical devices. Subsequently, these devices may spawn innovative treatments of neurological diseases by the medical community in the future. Additionally, this project will engage K-12, undergraduate, and graduate students to inspire them to pursue careers in Regenerative Neural Engineering. In particular, this project will employ outreach activities and hands-on activities to actively recruit female, first generation, underrepresented, and veterans’ students into the project and prepare them to contribute to this exciting field. The PI’s overarching career goal is to establish a highly successful neural engineering research and training program within the Center for Biomedical Engineering and Science in the Department of Mechanical Engineering at the University of North Carolina, Charlotte. Towards this goal, the goal of this project is to investigate magnetic stimulation (MSTIM) induced myelination of axons by oligodendrocytes (OLs) and the signaling mechanisms of MSTIM in myelination. Demyelination of myelinated axons in the nervous system is a deleterious feature of neurological diseases and spinal cord injuries. However, damaged axons can be repaired (i.e., remyelinated) when endogenous oligodendrocyte progenitor cells (OPCs) differentiate into new myelinating oligodendrocytes (OLs). Remyelination of axons by endogenous OLs, however, is limited due to OPCs’ failure to differentiate OLs. Electrical activity of neurons plays a necessary role in OPC differentiation and myelination of axons by OLs. Neuromodulation, an emerging neurotechnology, excites or inhibits dysfunctional neuronal circuits to alter them into a more physiological state and can be an effective tool for inducing myelination. In vitro electrical stimulation (ESTIM) and optogenetic stimulation (OSTIM) of neurons have been found to increase neural activity and enhance myelination of axons, but are invasive methods. A similar technique, magnetic stimulation (MSTIM), is a non-invasive form of neuromodulation that also modulates neural activity. The Research plan is organized under three objectives: (1) establish an in vitro model of neural activity-dependent myelination by MSTIM, (2) investigate MSTIM induced differentiation of OPCs and myelination of axons, and (3) investigate the neurotrophic factors, and signaling molecules released from neurons and OPCs with MSTIM-induced myelination. Outcomes are expected to enable an understanding of the fundamental mechanisms of interactions between MSTIM and the nervous system.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.