THERMOREGULATORY RESPONSE TO FOCAL BRAIN ISCHEMIA

对局灶性脑缺血的体温调节反应

• 批准号: 2502937
• 负责人: John Wallace Kuluz
• 金额: $ 8.22万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2000-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2502937
• 关键词: artery occlusion; body temperature regulation; brain injury; cerebral artery; cerebral ischemia /hypoxia; cytokine; hyperthermia; immunocytochemistry; interleukin 1; interleukin 6; laboratory rat; pathologic process; pyrogens; reperfusion; ultrasound blood flow measurement

The principle investigator in this proposal, John Kuluz, MD, is a pediatric intensivist at the University of Miami School of Medicine who regularly cares for a large number of infants, children and adolescents with a variety of acute and chronic brain injuries. His dedication to improving the neurologic outcome of patients following ischemic and traumatic brain injury has motivated him to investigate important questions related to the care of these children in the basic science research laboratory of the Division of Pediatric Critical Care Medicine. However, Dr. Kuluz lacks formal training in neuroscience research methods and therefore has not been capable of designing and performing experiments aimed at uncovering the scientific mechanisms underlying his observations using his current elementary abilities. The broad, long-term objective of this proposal is to train this young clinician-scientist in a large number of basic science research methods and techniques, under the direct supervision of established senior investigators, so that he can embark of a full and productive research career, designing and completing future studies aimed at improving neurological outcome of brain-injured children. Disturbances in thermoregulation resulting in elevated temperature occur commonly after acute brain injury in humans and may delay or even impede neurologic recovery. The principle investigator has previously identified a robust thermoregulatory response to middle cerebral artery occlusion (MCAO) in rats, which result results in marked elevations in both rectal and brain temperature during and after the ischemic period. This phenomenon is rats appears to mimic the thermoregulatory response of humans to ischemic and traumatic brain injury. The major goal of this project is to enhance our understanding of the mechanisms and functional significance of the thermoregulatory response to focal brain ischemia in rats so that neurologic outcome following brain injury in humans can be maximized. The scientific goal of these experiments is to determine the endogenous pyrogen which is responsible for the increase in temperature during MCAO and whether this pyrogen plays a deleterious role in the pathogenesis of focal cerebral ischemia-reperfushion injury. Specific aims are: (1) to measure the changes in brain and body temperature during and for 3 days and up to 30 days after MCAO; (2) to measure the changes in regional cerebral blood flow during MCAO before and after the rise in temperature; (3) to determine the regional distribution, cellular origin(s) and temporal profile of synthesis of the responsible endogenous pyrogen during and after MCAO; and (4) to determine the role of the pyrogen in the thermoregulatory response to MCAO and whether the effects of this pyrogen on focal cerebral ischemia-reperfushion injury are temperature-dependent.

该提案的主要调查者，医学博士John Kuluz是一名 迈阿密大学医学院的儿科强化医师 经常照顾大量的婴儿、儿童和青少年 有各种急性和慢性脑损伤。他致力于 改善脑缺血后患者的神经学结局 创伤性脑损伤促使他研究重要的 基础科学中有关照顾这些儿童的问题 儿科危重病医学部研究实验室。 然而，库鲁兹博士缺乏神经科学研究方法方面的正式培训 因此一直不能设计和执行实验 旨在揭示他观察到的科学机制 利用他目前的基本能力。广泛而长期的目标是 这项建议是为了大量培养这位年轻的临床医生兼科学家 基础科学的研究方法和技术，在指导下 监督老牌高级调查员，这样他就可以开始 一个完整而富有成效的研究生涯，设计和完成未来 旨在改善脑损伤儿童的神经学结果的研究。 体温调节出现干扰，导致温度升高 通常在人类急性脑损伤后，可能会延迟甚至阻碍 神经康复。首席调查员之前已经确定 大脑中动脉闭塞时强大的体温调节反应 (MCAO)，导致双侧直肠明显抬高 以及缺血期期间和之后的大脑温度。这 现象是大鼠似乎模仿了体温调节反应 人类对脑缺血和创伤性损伤的认识。这一行动的主要目标是 项目的目的是增进我们对其机理和功能的了解 大鼠局灶性脑缺血体温调节反应的意义 从而使人类脑损伤后的神经学结果可以 最大化。这些实验的科学目标是确定 导致气温升高的内源性热原 以及这种热原是否在大脑中动脉阻塞中起有害作用。 局灶性脑缺血再灌流损伤的发病机制。具体目标 是：(1)测量大脑和体温的变化 MCAO后3天至30天；(2)测量大脑中动脉的变化 大脑中动脉阻塞前后局部脑血流量升高 温度；(3)确定区域分布，蜂窝 负责任内源性合成的起源(S)及其时间分布 MCAO期间和术后的热原；以及(4)确定热原在大脑中动脉阻塞中的作用 热原在大脑中动脉阻塞时体温调节反应中的作用 这种热原对局灶性脑缺血再灌流损伤的作用如下 依赖于温度。