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药物来治疗多发性硬化症（MS）患者，从而减少甚至可能预防对他们大脑的永久性损伤。多发性硬化症会在大脑内引起炎性病变，这会对脆弱的脑组织造成不可逆转的损害，要么导致神经纤维失去髓鞘绝缘层，要么导致神经纤维死亡。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，但我们的证据表明，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，以至于血液不能足够快地提供氧气。为了找到答案，我们建议在全身麻醉下，在大鼠脊髓的一部分诱导一个模仿MS病变的小炎症病变。病变很小，而且放置得很小心，大鼠根本没有表现出任何症状，但病变足够大，在显微镜下可以清楚地看到。患有病变的大鼠将接受多种不同疗法中的一种治疗，以减少炎症造成的损害。通过比较治疗和未治疗的病变的大小和性质，将在显微镜下评估治疗的效果。这种治疗方法是基于一种信念，即改善发炎组织的氧合将有助于它在恶劣的炎症条件下存活下来。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起的损伤。一个重要的目标是利用脑部扫描仪获得病变性质的信息，就像医院使用的那样。原因是，如果知道实验性病变的性质，大脑扫描可以用来区分那些具有相似病变的患者，然后将有可能将有效的治疗方法应用于预期从中受益的特定患者。目前，特定类型的病变只能在死亡后或在手术中取出脑组织后通过显微镜检测到。如果这项研究取得成功，它将导致一种新的有效的治疗方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.