Defining microvascular structure and function in the aged cervical spinal cord

定义老年颈脊髓的微血管结构和功能

• 批准号: 10453217
• 负责人: ZIN Z KHAING
• 金额: $ 7.82万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-15 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10453217
• 关键词: Accident and Emergency department; Acute; Address; Adult; Age; Age-Years; Aging; Anatomy; Area; Area Under Curve; Astrocytes; Blood Flow Velocity; Blood Vessels; Blood Volume; Blood capillaries; Blood flow; Bolus Infusion; Brain; Centers for Disease Control and Prevention (U.S.); Cerebral cortex; Cerebrovascular Circulation; Cervical; Cervical spinal cord structure; Cervical spine; Characteristics; Contusions; Doppler Ultrasound; Drops; Female; Forelimb; Foundations; Goals; Health; Histologic; Human; Hypoxia; Image; Imaging Techniques; Inflammation; Injury; Kinetics; Knowledge; Label; Lasers; Lectin; Legal patent; Lesion; Measures; Metabolic; Methods; Microcirculation; Microglia; Microvascular Dysfunction; Nature; Nutrient; Older Population; Outcome; Oxygen; Perfusion; Persons; Population; Pre-Clinical Model; Rattus; Recovery of Function; Reporting; Resistance; Resolution; Rodent; Rodent Model; Severities; Spinal; Spinal Cord; Spinal cord injury; Structure; Surface; Techniques; Technology; Testing; Thick; Time; Tissues; Trauma; Ultrasonography; United States; Vascular blood supply; Work; age group; age related; aged; aging brain; behavior test; contrast enhanced; density; falls; gray matter; hemodynamics; human model; human old age (65+); hypoperfusion; image processing; imaging modality; improved functioning; innovation; intravital imaging; ischemic injury; locomotor deficit; male; normal aging; novel; older patient; preclinical study; primary outcome; response; sex; two-photon; white matter

Abstract The older population (≥65 years old) represents the fastest growing age group in the United States. According to the Centers for Disease Control and Prevention, the number of people 65 years of age or older living in the United States is projected to double by 2030 to 72 million adults, representing 20% of the total U.S. population [1]. Normal aging results in a nearly 30% reduction of microvasculature in the cerebral cortex with significant drops in capillary density, vascular responses to metabolic demand, and reduced angiogenic capabilities. This phenomenon of reduced blood vessel density and blood supply in normal aging is thought to underlie the “sensitive” nature of the aging brain to ischemic injuries. The aged spinal cord is also vulnerable to injuries; in recent years, ground levels falls resulting in spinal cord injuries (SCI) are among the most common trauma suffered by older patients presenting to the emergency room. Unfortunately we know next to nothing about how spinal cord microvasculature and hemodynamic changes with age. The present study aims to address this knowledge gap. We hypothesize that there are significant alterations to the microvasculature in the cervical spine with aging, which confer increased vulnerability to injuries. Our group has recently developed novel methods, using powerful intravital ultrafast contrast enhanced ultrasound (CEUS) imaging, to visualize blood flow within the microvasculature with unparalleled temporal (30,000 frames per second) and spatial (down to 50 micron) resolution. An important departure from other imaging modalities, where microvascular flow is examined just a few hundred microns deep from the surface of the tissue (e.g., laser speckle and two photon imaging), ultrafast CEUS imaging allows us to examine intraparenchymal microvascular structure and blood flow hemodynamics within the entire depth of the spinal cord tissue in real- time. We will apply this innovative intravital imaging to study 1) intraspinal microvasculature anatomy and function during normal aging, and 2) age-related microvascular vulnerabilities after tSCI. Additionally, cerebral blood flow and microvascular density differences have been detected between males and females in both human and rodent models. Therefore, microvascular changes during normal aging will be examined in both sexes. Results from this study will be foundational to understanding sex and age-related alterations in both the static and dynamic microvascular function of the spinal cord.

抽象的 据统计，老年人口（≥65 岁）是美国增长最快的年龄组。 向疾病控制和预防中心报告，居住在 65 岁或以上的人口数量 预计到 2030 年，美国成年人数量将翻一番，达到 7200 万，占美国总人口的 20% [1] 正常衰老导致大脑皮层微血管减少近 30%，且显着减少。 毛细血管密度下降、血管对代谢需求的反应以及血管生成能力降低。 正常衰老过程中血管密度和血液供应减少的现象被认为是造成这种现象的原因 老化的大脑对缺血性损伤“敏感”，老化的脊髓也容易受到损伤； 近年来，地面坠落导致脊髓损伤（SCI）是最常见的创伤之一 不幸的是，我们对到急诊室就诊的老年患者几乎一无所知。 本研究旨在解决脊髓微血管和血流动力学如何随年龄变化的问题。 我们认为微血管系统发生了重大变化。 颈椎随着年龄的增长，导致我们团队最近更容易受伤。 开发了新方法，使用强大的活体超快对比增强超声 (CEUS) 成像，以无与伦比的时间可视化微血管内的血流（每帧 30,000 帧） 第二）和空间（低至 50 微米）分辨率与其他成像方式的重要区别， 在距离组织表面仅几百微米深的地方检查微血管血流（例如， 激光散斑和双光子成像），超快 CEUS 成像使我们能够检查实质内 脊髓组织整个深度内的微血管结构和血流动力学 我们将应用这种创新的活体成像来研究 1) 脊柱内微血管解剖学和 正常衰老过程中的功能，以及 2) tSC​​I 后与年龄相关的微血管脆弱性。 男性和女性的脑血流量和微血管密度存在差异 因此，将在人类和啮齿动物模型中检查正常衰老过程中的微血管变化。 这项研究的结果将为理解性别和年龄相关的变化奠定基础。 脊髓的静态和动态微血管功能。