A novel central circuit involved in paradoxical thermoregulatory inversion and induction of torpor-like state

项目摘要 为了维持哺乳动物的体温(TCORE)，中枢神经系统 体温调节网络对皮肤降温的反应是通过增加棕色脂肪组织和 发抖发热，并通过皮肤血管收缩减少热量损失。然而， 在几种情况下(如冬眠、麻木、快速眼动睡眠)，这些“标准” 用来保护TCORE的体温调节反应似乎被“体温调节”所取代 冷暴露导致产热抑制和热暴露的反转 刺激生热作用。我们假设POA体温调节功能的阻断是 启动温度调节反转所需的，以及这种自相矛盾的 体温调节受一条新的中枢体温调节通路控制。我们将在 麻醉大鼠的活体神经生理学研究，平行演示 自由行为大鼠模型的体温调节反转以及最新的解剖学研究 了解调节体温调节倒置的相关神经通路。本研究 将开辟体温调节研究的新领域，并将阐明一种新的机制 快速、可控、稳定、可逆亚低温诱导治疗脑缺血 治疗中风、脑损伤和阻止持续的神经性高烧。

Project Summary To maintain body core temperature (TCORE) in mammals, the central nervous system thermoregulatory networks respond to skin cooling by increasing brown adipose tissue and shivering thermogenesis, and by reducing heat loss via cutaneous vasoconstriction. However, there are several conditions (e.g., hibernation, torpor, REM sleep) in which these “standard” thermoregulatory responses to protect TCORE appear to be superseded by a “thermoregulatory inversion” in which cold exposure causes inhibition of thermogenesis and warm exposure stimulates thermogenesis. We hypothesize that blockade of POA thermoregulatory function is required for the initiation of thermoregulatory inversion and that such paradoxical thermoregulation is governed by a new central thermoregulatory pathway. We will employ in vivo neurophysiological studies in anesthetized rats, a parallel demonstration of thermoregulatory inversion in a free-behaving rat model, and state-of-the-art anatomical studies to understand the relevant neural pathways regulating thermoregulatory inversion. This study will open a new field of research in thermoregulation and will elucidate a new mechanism for a rapid, controllable, stable and reversible induction of hypothermia for the treatment of ischemic stroke, brain trauma and to block persistent, high neurogenic fevers.