Adaptation, plasticity and phylogeny: factors mediating tissue oxygen homeostasis

适应、可塑性和系统发育：介导组织氧稳态的因素

• 批准号: 386056-2010
• 负责人: Dunn, Jeff
• 金额: $ 2.55万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=528728
• 关键词: Adaptation; plasticity; phylogeny; factors; mediating

The long term objective of this program is to understand how tissues adapt to changes in oxygen delivery and utilization in terms of the oxygen homeostasis. A unique multimodal system will be used to assess tissue oxygenation. This combines Magnetic Resonance Imaging with near-infrared (NIR) spectroscopy and implantable interstitial sensors (for partial pressure of oxygen (pO2)). We will determine the relationship between tissue oxygenation (defined as either hemoglobin saturation, interstitial pO2, or the level of hypoxia needed to cause increased lactate or the binding of histological hypoxia markers) and cerebral metabolic rate for oxygen (CMRO2) before and after adaptation to chronic hypoxia in the rat model. We will thus identify the level of hypoxia that will inhibit CMRO2 and how the acute response is modified by chronic adaptation. We will determine the effects of chronic increased CMRO2 (induced with experimental seizures) on tissue oxygenation as measured with the multimodal system. We will use a phylogenic approach to help determine the capacity for brain oxygenation to adapt. Here we will compare brain pO2 over a range of inspired oxygen levels in lowland birds with that of the bar-headed goose. This animal is adapted for flight at high altitudes and hypoxic conditions. We have developed a unique pO2 sensor that can be implanted chronically and used in awake unrestrained animals. This will reduce artifacts related to acute tissue damage as well as anesthesia. This study will determine if adaptation results in normalization of brain oxygen levels during hypoxia, or a tolerance to reduced levels. We will determine if cell oxygen sensing will adapt in a model of chronic hypoxia exposure. The hypoxia inducible factor (HIF) pathway is regulated by pathways sensitive to intracellular oxygen. We will quantify HIF concentration before and after adaptation and relate to tissue pO2 to show if regulation of this path is modified by chronic hypoxia. This work will provide unique information on how brain oxygenation is influenced by acute and chronic hypoxia and the capacity of brain to adapt to hypoxia.

该程序的长期目标是了解组织如何根据氧稳态来适应氧气递送和利用的变化。 独特的多模式系统将用于评估组织氧合。这将磁共振成像与近红外（NIR）光谱和可植入的间质传感器（用于氧气（PO2）的部分压）。 We will determine the relationship between tissue oxygenation (defined as either hemoglobin saturation, interstitial pO2, or the level of hypoxia needed to cause increased lactate or the binding of histological hypoxia markers) and cerebral metabolic rate for oxygen (CMRO2) before and after adaptation to chronic hypoxia in the rat model.因此，我们将确定将抑制CMRO2的缺氧水平以及如何通过慢性适应来改变急性反应。我们将确定慢性增加的CMRO2（用实验性癫痫发作）对用多模式系统测量的组织氧合的影响。 我们将使用系统发育方法来帮助确定脑氧合适应的能力。在这里，我们将在低地鸟类的一系列启发氧气中比较脑PO2和棒状鹅的氧气水平。该动物适合在高海拔和低氧条件下飞行。我们已经开发了一种独特的PO2传感器，该传感器可以长期植入并用于清醒的无情动物中。这将减少与急性组织损伤以及麻醉有关的伪影。这项研究将确定适应性是否导致缺氧期间脑氧水平的归一化，或者对降低水平的耐受性。我们将确定细胞氧气是否会适应慢性缺氧模型。低氧诱导因子（HIF）途径受对细胞内氧敏感的途径调节。 我们将在适应之前和之后定量HIF浓度，并与组织PO2相关，以显示该路径的调节是否通过慢性缺氧修饰。这项工作将提供有关脑氧合如何受急性和慢性缺氧以及大脑适应缺氧的能力影响的独特信息。