Evaluation of combined mild hypothermia and magnesium as a neuroprotective therapy following cerebral ischaemia/stroke

中风-脑缺血每年影响50,000多名澳大利亚人，是澳大利亚导致残疾的主要原因，也是仅次于心脏病的第三大死亡原因。大约25%的中风患者在一个月内死亡，而大多数幸存者由于语言、记忆、思维过程、视力、平衡或肢体运动控制受损(瘫痪)而致残。澳大利亚社区每年因中风-脑缺血造成的直接和间接损失超过20亿美元。一旦中风发生，抑制或限制大脑损伤的能力将减少中风对患者和澳大利亚社区的破坏性影响。尽管进行了几十年的研究，但还没有完全令人满意的药物可以直接抑制中风后的脑损伤；寻找新的治疗方法是至关重要的。当整个大脑的血液供应减少时，就会发生中风(全局性脑缺血；心脏骤停、闭合性头部损伤)或大脑的特定区域，通常是由于大脑动脉阻塞(局灶性脑缺血或血栓栓塞性中风)。该项目将评估镁和亚低温(35)联合治疗方案在局灶性和全局性脑缺血动物模型中减少脑损伤的效果。这项工作源于我们最近的数据，首次表明镁在低温下只对脑缺血后的动物具有神经保护作用。因此，我们的数据表明，镁与低温相结合是一种有效的中风治疗方法。此外，镁-亚低温治疗有几个吸引人的地方。这两家公司都可能有多种行动机制，管理成本低，而且安全。重要的是，该项目的实验结果将使更好地设计未来的临床试验，以测试镁-适度低温组合的有效性，以改善中风后患者的预后。

Stroke-cerebral ischaemia affects over 50,000 Australians every year and is Australia's leading single cause of disability and third greatest cause of death after heart disease. About 25% of people who suffer a stroke die within one month while most survivors are disabled because of impaired speech, memory, thought processes, vision, balance, or motor control of the limbs (paralysis). The direct and indirect cost of stroke-cerebral ischaemia to the Australian community is over $2 billion annually. The ability to inhibit or limit brain damage once a stroke has occurred will reduce the devastating effects of stroke to patients and the Australian community. Despite decades of research, there is no totally satisfactory drug that directly inhibits brain damage following stroke; the search for new treatments is paramount. A stroke occurs when there is a reduced blood supply to the entire brain (global cerebral ischaemia; eg. cardiac arrest, closed head injury) or to a specific region of the brain, usually as a result of a blockage in a brain artery (focal cerebral ischaemia or thrombo-embolic stroke). This project will evaluate the efficacy of combined magnesium and mild hypothermia (35) treatment protocols to reduce brain damage in animal models of focal and global cerebral ischaemia. This work stems from our recent data showing for the first time that magnesium is only neuroprotective in animals following cerebral ischaemia when present with hypothermia. Thus our data indicates that magnesium, when combined with hypothermia is an effective stroke therapy. Moreover treatment with magnesium-mild hypothermia has several attractions. Both are likely to have multiple mechanisms of action, are cheap to administer and safe. Importantly, the experimental findings from this project will enable better design of future clinical trials to test the efficacy of combined magnesium-modest hypothermia to improve patient outcome following stroke.