THERMOREGULATORY RESPONSE TO FOCAL BRAIN ISCHEMIA

对局灶性脑缺血的体温调节反应

• 批准号: 2796980
• 负责人: John Wallace Kuluz
• 金额: $ 9.68万
• 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 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2796980
• 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.

这项提案的主要研究者，医学博士约翰·库鲁兹，是一位 迈阿密大学医学院的儿科重症监护医生， 定期照料大量婴儿、儿童和青少年; 各种急性和慢性脑损伤他致力于 改善缺血性脑卒中后患者的神经学结局， 创伤性脑损伤促使他研究重要的 在基础科学方面与照顾这些儿童有关的问题 儿科重症监护医学部的研究实验室。 然而，库鲁兹博士缺乏神经科学研究方法方面的正规培训 因此无法设计和进行实验 旨在揭示他的观察背后的科学机制 用他现在的基本能力广泛的长期目标 这个提议是要大量培训这位年轻的临床科学家， 基础科学研究方法和技术，在直接 监督既定的高级调查员，使他能够着手 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功能结果的研究。 体温调节紊乱导致体温升高 通常发生在人类急性脑损伤后， 神经恢复首席调查员之前已经确认 对大脑中动脉闭塞的强烈体温调节反应 （MCAO），这导致大鼠直肠和 以及缺血期间和之后的脑温度。这 现象是大鼠似乎模仿的体温调节反应， 缺血性和创伤性脑损伤。这个项目的主要目标是 项目是为了提高我们的机制和功能的理解 局部脑缺血时体温调节反应的意义 大鼠，以便在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 导致温度升高的内源性热原 以及这种热原是否在MCAO中起有害作用， 局灶性脑缺血再灌注损伤的发病机制具体目标 （1）测量脑温和体温的变化， MCAO后3天至30天;（2）测量MCAO后 局部脑血流量在MCAO之前和之后的上升， （3）确定区域分布，细胞 负责的内源性合成的来源和时间概况 MCAO期间和之后的热原;以及（4）确定 热原在MCAO体温调节反应中的作用以及 该热原对局灶性脑缺血再灌注损伤的作用机制 依赖于温度。