Elucidating torpor's effects on brain activity and behaviour and investigating its neuroprotective properties against acute ischaemic stroke

阐明麻木对大脑活动和行为的影响并研究其对急性缺血性中风的神经保护特性

• 批准号: MR/S001948/1
• 负责人: Yige Huang
• 金额: $ 36.16万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS001948%2F1
• 关键词: Elucidating; torpor; effects; brain; activity

Stroke is a leading cause of adult disability and death globally. It occurs when a clot forms in blood vessels in the brain. The affected area of brain is starved of oxygen, leading to the death of brain cells. The result is often life-changing disability or death. Thrombolysis, a drug treatment that dissolves the clot, has proven to be very effective against stroke. However, the time window in which it can be used is short (4.5 hours). Therefore, stroke scientists have been researching new methods of treating stroke that may complement thrombolysis and improve outcome in post-stroke patients. Research in animals shows that hypothermia is the most effective neuroprotective therapy (i.e. a treatment that protects brain cells from damage e.g. due to a stroke). However, current ways of triggering hypothermia (e.g. cooling the body's surface using a cooling blanket) lead to thermogenesis. This is a response that involves shivering (which is unpleasant for the patient) and, more importantly, increases the body's production of heat and which opposes the effect of cooling. However, in nature there is a way of triggering hypothermia that reduces thermogenesis: torpor.Torpor is a reversible regulated state of reduced body temperature and metabolism. It occurs naturally in some animals in response to food shortage. Hibernation is the name of one form of profound torpor that occurs seasonally. However, recent research has shown that particular drugs can be used to trigger torpor in animals that do not naturally go into torpor. Other research has shown that even some primates naturally go into torpor. As a result, there is growing promise that the neuroprotective properties of torpor can be harnessed to develop new effective treatments for stroke. However, before this can happen, several questions need to be answered:1) How does torpor affect brain activity? 2) How does torpor affect brain function?3) Does inducing torpor using drugs protect the brain against damage resulting from a stroke?In order to investigate these questions, the following experiments will be performed in mice:1) Recording of brain activity during torpor2) Assessing how performance in a tests of brain function is affected by torpor 3) Assessing how torpor affects the extent of brain damage and impairment of function that would be caused by a stroke

中风是全球成年人残疾和死亡的主要原因。当大脑血管中形成血块时，就会发生这种情况。受影响的大脑区域缺氧，导致脑细胞死亡。结果往往是改变生活的残疾或死亡。溶栓是一种溶解凝块的药物治疗，已被证明对中风非常有效。然而，它可以使用的时间窗口很短（4.5小时）。因此，脑卒中科学家一直在研究治疗脑卒中的新方法，以补充溶栓并改善脑卒中后患者的预后。动物研究表明，低温是最有效的神经保护疗法（即保护脑细胞免受中风等损伤的治疗）。然而，目前触发体温过低的方法（例如，使用冷却毯冷却体表）会导致生热。这种反应包括颤抖（这对病人来说是不舒服的），更重要的是，它增加了身体产生的热量，与降温的效果相反。然而，在自然界中，有一种触发体温过低的方法可以减少生热作用：麻木。昏睡是一种体温和新陈代谢降低的可逆调节状态。这在一些动物体内自然发生，以应对食物短缺。冬眠是一种季节性的深度麻木状态。然而，最近的研究表明，特定的药物可以用来引发动物的麻木，而这些动物不会自然进入麻木状态。其他研究表明，即使是一些灵长类动物也会自然地进入昏睡状态。因此，越来越多的人希望利用睡眠的神经保护特性来开发新的有效的中风治疗方法。然而，在这种情况发生之前，有几个问题需要回答：1)麻木是如何影响大脑活动的？2)麻木如何影响大脑功能？3)用药物诱导昏睡能保护大脑免受中风造成的损伤吗？为了研究这些问题，我们将在小鼠身上进行以下实验：1)记录冬眠时的大脑活动2)评估冬眠如何影响大脑功能测试的表现3)评估冬眠如何影响中风引起的脑损伤和功能损害的程度

项目成果

The relationship between fasting-induced torpor, sleep, and wakefulness in laboratory mice.

禁食引起的torpor，睡眠和实验室小鼠的清醒之间的关系。

• DOI: 10.1093/sleep/zsab093
• 发表时间: 2021-09-13
• 期刊: Sleep
• 影响因子: 5.6
• 作者: Huang YG;Flaherty SJ;Pothecary CA;Foster RG;Peirson SN;Vyazovskiy VV
• 通讯作者: Vyazovskiy VV

The hypothalamic link between arousal and sleep homeostasis in mice.

• DOI: 10.1073/pnas.2101580118
• 发表时间: 2021-12-21
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Yamagata T;Kahn MC;Prius-Mengual J;Meijer E;Šabanović M;Guillaumin MCC;van der Vinne V;Huang YG;McKillop LE;Jagannath A;Peirson SN;Mann EO;Foster RG;Vyazovskiy VV
• 通讯作者: Vyazovskiy VV

The relationship between fasting-induced torpor, sleep and wakefulness in the laboratory mouse

实验小鼠禁食引起的麻木、睡眠和觉醒之间的关系

• DOI: 10.1101/2020.05.05.076570
• 发表时间: 2020
• 作者: Huang Y