Pharmacological modulation of microglial responses after transient forebrain ischaemia in rats

大鼠短暂前脑缺血后小胶质细胞反应的药理学调节

• 批准号: nhmrc : 143624
• 负责人: Prof Bevyn Jarrott
• 金额: $ 11.4万
• 依托单位: Monash University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/pharmacological-modulation-microglial-ischaemia-rats/99186
• 关键词: Pharmacological; modulation; microglial; responses; after

A stroke is caused by an acute blockade of blood flow to a brain region and is normally caused by a clot in the artery that supplies blood to that region. Within minutes, the region of the brain that is receiving no blood flow, dies and so the functions controlled by that region cease. If this region controls key functions such as breathing then the patient dies and this occurs in about one third of patients. However, in the majority of patients, the blockage affects parts of the brain controlling movement of limbs or speech and so these patients suffer permanent disabilities. Not surprisingly, stroke is the most common life-threatening neurological disease and the major cause of disability in adults over 45. Apart from the profound effect stroke has on the patient and the family, the annual cost of disability to the Australian community is approx $ 1 billion. If the disability could be minimised by reducing institutionalization then the cost saving would be great. Research is being carried out to define how nerves die when they have insufficient blood supply and progress has been made in understanding the biochemical basis of this process. Such knowledge opens the way for the design of novel drugs to delay nerve death. Our laboratory has been successful in designing a novel drug, AM-36 that minimises nerve death in the forebrain of rats that have had the blood supply to the forebrain interrupted for 3 to 5 hours. A recent report has shown that a stroke in the forebrain can lead to nerve damage in the spinal cord and this could contribute to impaired walking in stroke patients. This is an unexpected finding and this project seeks to define how and when nerves in the spine die after a stroke in the forebrain. Such information should then lead to the rational design of drugs to minimise the death of nerves in the spinal cord as well as in the forebrain.

中风是由流向大脑区域的血液的急性阻塞引起的，通常是由向该区域供血的动脉中的凝块引起的。几分钟内，大脑中没有血液流动的区域就会死亡，因此该区域控制的功能就会停止。如果这个区域控制着呼吸等关键功能，那么病人就会死亡，大约三分之一的病人会死亡。然而，在大多数患者中，阻塞会影响控制肢体运动或语言的大脑部分，因此这些患者会遭受永久性残疾。毫不奇怪，中风是最常见的危及生命的神经系统疾病，也是45岁以上成年人残疾的主要原因。除了中风对患者和家庭的深远影响外，澳大利亚社区每年因残疾而造成的损失约为10亿美元。如果残疾可以通过减少机构化来最小化，那么节省的成本将是巨大的。目前正在进行研究，以确定神经在血液供应不足时是如何死亡的，并且在理解这一过程的生化基础方面取得了进展。这些知识为设计新型药物以延缓神经死亡开辟了道路。我们的实验室已经成功地设计了一种新药AM-36，它可以最大限度地减少前脑血液供应中断3到5小时的大鼠前脑的神经死亡。最近的一份报告表明，前脑中风可能导致脊髓神经损伤，这可能导致中风患者行走障碍。这是一个意想不到的发现，该项目旨在确定前脑中风后脊柱中的神经如何以及何时死亡。这些信息将引导药物的合理设计，以最大限度地减少脊髓和前脑神经的死亡。