Development of magnetic force biotechnology to facilitate neural regeneration

中枢神经系统（CNS）由大脑和脊髓组成，负责协调我们整个身体的活动。这种协调需要数十亿个神经元（神经细胞）之间的精确连接，有时距离长达0.5米。这些连接是由被称为轴突的又长又细的纤维构成的，轴突从细胞体伸出，允许电脉冲在神经元之间传递（有点像连接计算机部件的电路）。中枢神经系统中神经回路的损伤可由急性创伤（例如脊髓损伤）或帕金森病等神经系统疾病的发展引起。在中枢神经系统中，是脊髓包含控制复杂运动（如行走）的神经元回路。不幸的是，中枢神经系统中轴突的自然再生能力极其有限，因此由大脑或脊髓损伤引起的功能缺陷可能无限期地持续下去。目前，全世界有数百万人生活在这种损伤的致残影响中，因此，迫切需要找到能够恢复这些神经连接的潜在治疗方法的新方法。该项目建立在先前成功的合作基础上，利用物理科学和生物工程方法利用远程磁力操纵神经元。在这里，我们将研究磁力方法是否可以用于远程引导轴突重新生长，重新连接神经回路和恢复功能。为此，我们将设计和开发新的可控磁力装置。我们将使用这些系统来瞄准特殊的微观磁性纳米颗粒，这些纳米颗粒装载在轴突的细胞内区室中，称为核内体。此外，我们将探索利用先进的基因修饰技术制备能够在内部生物合成磁性纳米颗粒的神经细胞。为了验证这些方法，我们将研究磁力对脊髓损伤的新型生物模型的影响，该模型结合了从大鼠皮层和脊髓培养的活组织切片。该项目将汇集一个广泛的跨学科团队，在物理和材料科学、神经科学、电生理学、合成生物学和神经外科方面具有专业知识。如果成功，该项目将为将方法转化为脊髓损伤的临床前和最终临床治疗提供关键的基础技术。它还将对神经科学和神经系统疾病的其他领域的研究产生重大影响，这些领域试图重建中枢神经系统的回路，比如帕金森氏病。

The central nervous system (CNS) consists of both the brain and spinal cord and is responsible for co-ordinating activity across our entire body. Such co-ordination requires the precise connections of billions of neurons (nerve cells), sometimes across distances of up to 0.5 metres long. These connections are made using long, thin fibres known as axons, which project from the cell body and allow the transport of electrical impulses between the neurons (somewhat like the electrical circuits that connect components in a computer).Damage to the neural circuitry in the CNS can be caused by acute trauma (for example spinal cord injury) or following the development of neurological disorders such as Parkinson's disease. Within the CNS, it is the spinal cord that contains the neuronal circuits that govern complex movements such as walking. Unfortunately, the ability of axons in the CNS to naturally regenerate is extremely limited, and so the functional deficits that result from damage to the brain or spinal cord, can persist indefinitely. Millions of people worldwide are currently living with the disabling effects of such damage, and so new approaches to find potential treatments that could restore these neural connections are desperately needed.This project builds on a previously successful collaboration to use physical sciences and bioengineering approaches to manipulate neurons using remote magnetic forces. Here we will investigate whether magnetic force methods could be used to remotely guide axon re-growth to reconnect neural circuits and restore function. To do this we will design and develop new controllable magnetic force devices. We will use these systems to target specialist microscopic magnetic nanoparticles loaded into intracellular compartments in the axons known as endosomes. In addition, we will explore the use of advanced genetic modification techniques to prepare neuronal cells that can biosynthesize magnetic nanoparticles internally. To test these methodologies, we will investigate the effects of magnetic forces on a novel biological model of spinal cord injury, that incorporates living sections of tissue cultured from the rat cortex and spinal cord.The project will bring together a wide-reaching, cross-disciplinary team with expertise in physics and materials science, neuroscience, electrophysiology, synthetic biology, and neurosurgery. If successful, the project will provide the crucial foundation technology required to translate the methods towards pre-clinical and ultimately clinical treatments of spinal cord injury. It will also have significant impact on research in other areas of neuroscience and neurological disorders which seek to re-establish circuits in the CNS, such as Parkinson's disease.