Enhancing axon growth and functional recovery after cerebral ischemia (stroke)

大脑一侧的异常血流(由于血栓或出血)被称为中风，通常会导致身体另一侧的残疾。如果在受伤后几个小时进行治疗，就需要发挥作用，因为通常情况下，入院和诊断都会延迟。中风主要影响老年人，但很少有研究在老年模型系统中检查中风的潜在治疗方法。令人鼓舞的是，最近的研究表明，即使是年迈的大脑和脊髓也有一定的适应中风的能力。然而，目前还没有针对中风的恢复性疗法。我们之前已经证明，一种名为软骨素酶ABC的药物可以促进受损神经纤维的生长，并可以恢复成年大鼠脊髓损伤后失去的功能。到目前为止，软骨素酶ABC促进卒中后神经和功能恢复的潜力还没有被检验。我们建议在这里调查这件事。我们的研究旨在通过大脑和脊髓的备用(未受伤)神经纤维来鼓励代偿，从而克服中风导致的肢体功能障碍。为了模拟老年人的中风，将在麻醉的老年大鼠的大脑中诱导一个小中风。术后将给予止痛。联合治疗将在一周后开始。为了促进大脑对侧(未受伤)神经纤维的生长，软骨素酶ABC将被注射到大脑和脊髓的区域。老鼠将被安置在已知的环境中，以鼓励受伤的前爪康复。其他大鼠将作为对照，以确定联合治疗的每一部分的效果。每周将对大鼠进行测试，以评估接受治疗的大鼠的恢复情况。五周后，将进行管路追踪，以确定未受伤的神经纤维是否对治疗有反应。两周后，将对大鼠进行终末麻醉，以提供组织进行分析。我们将寻找证据，证明联合治疗导致神经纤维连接的变化，这可能解释观察到的任何行为改善。结果将在任何出版禁令解除后，通过我们的公关部批准的新闻发布向公众公布。我们还将联系全国性报纸以及包括《新科学家》在内的杂志的科学记者。我还参加了对市中心学校的外联活动，讨论中风的风险因素，涉及负责任地使用动物的工作，以及中风的潜在治疗方法。

Abnormal blood flow to one side of the brain (due to clots or bleeds) is called stroke and often causes disability in the opposite side of the body. Therapies need to work when given many hours after injury, because there is typically a delay to admission to hospital and diagnosis. Stroke primarily affects elderly people, yet few studies have examined potential therapies for stroke in an aged model system. Encouragingly, recent research shows that even aged brains and spinal cords have some capacity for adapting to stroke. There are, however, no restorative therapies for stroke. We have previously shown that a drug, called chondroitinase ABC, can boost growth of injured nerve fibers and can restore function lost after spinal cord injury in adult rats. To date, the potential of chondroitinase ABC for promoting neural and functional recovery after stroke has not been examined. We propose investigating this here. Our study aims to overcome stroke-induced disabilities in limb function by encouraging compensation by spared (uninjured) nerve fibers of the brain and spinal cord. To simulate stroke in elderly people, a small stroke will be induced in the brain of anaesthetised elderly rats. Post-operative analgesia will be given. Combination therapy will be initiated one week later. To boost growth of nerve fibers from the opposite (uninjured) side of the brain, chondroitinase ABC will be injected into regions in the brain and spinal cord. Rats will be housed in environments known to encourage rehabilitation of the injured forepaw. Other rats will be used as controls in order to determine the effect of each part of the combination therapy. Rats will be tested weekly to assess recovery in rats treated with the therapies. After five weeks, tract tracing will be performed to determine whether uninjured nerve fibres have responded to treatment. Two weeks later, rats will be terminally anaesthetised to provide tissue for analysis. We will seek evidence that the combination therapy induced changes in nerve fiber connections that might explain any behavioural improvements observed. Results will be communicated to the general public after any publication embargo is lifted via press release sanctioned by our public relations department. We will also contact science reporters at national newspapers as well as magazines including New Scientist. I also participate in outreach to inner city schools, discussing risk factors for stroke, work involving responsible use of animals and potential therapies for stroke.