A compartmentalised chamber for the in vitro study and manipulation of axon degeneration.

神经系统疾病占全球疾病负担的近10%。人们已经进行了大量的研究，试图了解神经细胞在不同情况下（如中风、创伤性脑损伤或阿尔茨海默病）是如何死亡的？的疾病。研究人员使用动物，最常见的是大鼠和小鼠，来模拟这些条件的各个方面，试图了解神经细胞如何免受退化和死亡的影响。许多研究都集中在神经细胞体上，而很少有人关注神经细胞的其他部分：轴突，一个神经将大脑的一个区域连接到另一个区域的精细过程，或者与其他神经细胞接触的突触。显然，不仅保护神经细胞体，而且保护突触和轴突也很重要，因为在某些疾病中，神经元的这些部分可能首先受到损伤，随后神经细胞体死亡。我们可以在整个动物身上进行更多的实验，但显然最好是在培养中进行实验，以减少和取代对整个动物实验的需要。尽管我们对轴突或突触退化所涉及的分子途径知之甚少，但我们确实知道它涉及可以被抑制的活性生化途径。了解这些途径可能为治疗干预提供新的途径。我们将建造一个设备，使我们能够在培养室中培养神经细胞，这样神经细胞体就在一个隔间中，轴突将通过非常小的孔生长到另一个隔间中。轴突只能在培养室底部的粘性条纹上生长，这样它们就能像在动物大脑中一样形成束。由于两个隔室之间的孔非常小，每一侧的流体环境可以独立地改变，再次模仿大脑环境的另一个方面。一旦我们完善了这个用于生长神经元的腔室系统，我们将进行一项实验，使用药物来操纵轴突生物学，并测试我们是否可以保护它们免受伤害。我们认为这些实验将展示该系统的优势，并鼓励其他科学家在研究中使用该设备，减少对动物的使用。

Diseases of the nervous system account for nearly 10% of the global burden of disease. An enormous amount of research has been undertaken to try and understand how and why nerve cells die in different conditions such as stroke, traumatic brain injury or Alzheimer?s disease. Researchers have used animals, most commonly rats and mice, to mimic aspects of these conditions to try and understand how nerve cells might be protected from degeneration and death. Much work has focussed on the nerve cell body and much less attention has been paid to other parts of the nerve cell: the axon, the fine process by which one nerve connects one region of the brain to another, or the synapse which makes contact with other nerve cells. It is clear that it is important to protect not only the nerve cell body but also the synapse and the axon since in some diseases these parts of the neuron may be the first to be injured with subsequent death of the nerve cell body. We could carry out more experiments in whole animals but it is clearly preferable to do experiments in culture and to reduce and replace the need for whole animal experiments.Although we know little about the molecular pathways that are involved in axon or synapse degeneration we do know that it involves active biochemical pathways that can be inhibited. Understanding these pathways may offer novel routes to therapeutic interventions. We will build a device that enables us to grow nerve cells in a culture chamber so that the nerve cell bodies are in one compartment and the axons will grow through very small holes into another compartment. The axons will only grow on sticky stripes printed on the bottom of the culture chamber so that they form bundles in the same way as they do in animals brains. Because the holes between the two compartments are so small, the fluid environment on each side can be changed independently, again mimicking another aspect of the brain environment. Once we have perfected this chamber system for growing neurons we will carry out an experiment using drugs to manipulate the axon biology and test if we can protect them from injury. We think these experiments will demonstrate the advantages of the system and will encourage other scientists to use this device in their research and reduce their use of animals.