To develop therapies and a strategy for their translation to treat early lesions in multiple sclerosis

我们的目标是开发一种治疗多发性硬化症(MS)患者的药物，以便减少甚至预防对他们大脑的永久性损害。多发性硬化症会导致大脑内的炎性病变，这可能会不可逆转地损害脆弱的脑组织，要么导致神经纤维失去髓鞘绝缘层，要么杀死神经纤维。这种损害会导致毁灭性的症状，包括失明、瘫痪和麻木。炎症损害大脑的原因尚不清楚，但我们的证据是，缺氧可能是问题的一部分。发炎的大脑可能会消耗太多的氧气，以至于血液无法足够快地提供氧气。为了找出答案，我们建议在全身麻醉下，在大鼠脊髓的部分区域诱导一种类似于多发性硬化症的小规模炎性病变。损伤很小，放置得很仔细，老鼠根本没有表现出任何症状，但损伤足够大，可以在显微镜下清楚地看到。有这种损伤的大鼠将接受一系列不同疗法中的一种，以减少炎症造成的损害。治疗的效果将通过比较治疗和未治疗的损伤的大小和性质在显微镜下进行评估。这些治疗是基于这样一种信念，即改善炎症组织的氧合将有助于它在恶劣的炎症条件下生存下来。一些治疗方法只是增加呼吸空气中的氧气供应，而另一些治疗方法则是通过治疗血管来增加向大脑的氧气输送。其他治疗方法试图保护发炎组织免受缺氧引发的损害。一个重要的目标是使用医院使用的脑部扫描仪获得有关病变性质的信息。原因是，如果已知实验性病变的特性，脑扫描可以用来区分那些有类似病变的患者，然后就有可能对预期受益的特定患者应用有效的治疗方法。目前，这种特殊类型的损伤只能在死亡后或在手术中取出脑组织后通过显微镜才能检测到。如果研究成功，将产生一种新的有效疗法来预防多发性硬化症的残疾。

We aim to develop a medicine to treat patients with multiple sclerosis (MS) so that permanent damage to their brain is diminished, or perhaps even prevented. MS causes inflammatory lesions within the brain and this can irreversibly damage the delicate brain tissue, either causing the nerve fibres to lose their insulating layer of myelin, or killing the nerve fibres. This damage causes the devastating symptoms, including blindness, paralysis and numbness. The reason inflammation damages the brain is not known but our evidence is that a lack of oxygen may be part of the problem. The inflamed brain may use so much oxygen that it cannot be provided fast enough by the blood. To find out, we propose to induce a small inflammatory lesion that mimics the MS lesion in part of the rat spinal cord, under general anaesthesia. The lesion is so small, and carefully placed, that the rats show no symptoms at all, but the lesion is sufficiently large to be able to see it clearly under the microscope. Rats with the lesion will be treated with one of a number of different therapies designed to reduce the damage caused by the inflammation. The efficacy of the therapy will be assessed microscopically by comparing the size and nature of the treated and untreated lesions. The treatments are based on a belief that improving oxygenation of the inflamed tissue will help it to survive the harsh conditions of the inflammation. Some treatments simply involve increasing the oxygen supply in the breathing air, while others are designed to increase the delivery of oxygen to the brain by treating the blood vessels. Other treatments attempt to protect the inflamed tissue from damaging events initiated by the shortage of oxygen. One important goal is to obtain information about the properties of the lesion using a brain scanner, as used in hospitals. The reason is that if the properties of the experimental lesion are known, brain scanning can be used to distinguish those patients with similar lesions, and then it will be possible to apply the effective therapies to the particular patients anticipated to benefit from them. At present the particular type of lesion can only be detected by microscopy, either after death, or after taking a piece of brain tissue out during an operation. If the research is successful it will result in a new and effective therapy to prevent disability in MS.