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中风、创伤性脑损伤或阿尔茨海默病等不同情况下死亡的方式和原因。年代的疾病。研究人员用动物，最常见的是大鼠和小鼠，来模拟这些情况的各个方面，试图了解神经细胞是如何免受退化和死亡的。很多工作都集中在神经细胞体上，而对神经细胞的其他部分的关注就少得多：轴突，一个神经连接大脑的一个区域到另一个区域的精细过程，或者与其他神经细胞联系的突触。很明显，不仅要保护神经细胞体，而且要保护突触和轴突，因为在某些疾病中，神经元的这些部分可能是神经细胞体随后死亡时首先受损的部分。我们可以在整个动物身上进行更多的实验，但显然更可取的是在培养中进行实验，以减少和取代对整个动物实验的需求。尽管我们对参与轴突或突触退化的分子途径所知甚少，但我们确实知道它涉及可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。我们将建造一种装置，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室中，轴突就会通过非常小的孔生长到另一个室中。轴突只会生长在打印在培养箱底部的粘性条纹上，这样它们就会像动物的大脑一样形成束状结构。因为两个隔室之间的孔非常小，两边的流体环境可以独立改变，再次模仿大脑环境的另一个方面。一旦我们完善了这个生长神经元的腔室系统，我们将进行一个实验，使用药物来操纵轴突生物学，并测试我们是否能保护它们免受伤害。我们认为这些实验将证明该系统的优点，并将鼓励其他科学家在他们的研究中使用该设备，减少他们对动物的使用。

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.