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 老年人（≥65岁）代表了美国增长最快的年龄段。根据 到疾病控制和预防中心，居住在65岁以上的人数 美国预计到2030至7200万成年人将翻一番，占美国总人口的20％ [1]。正常的衰老导致大脑皮层中微脉管系统的降低近30％，显着 毛细血管密度下降，对代谢需求的血管反应以及血管生成能力降低。这 正常衰老中血管密度和血液供应降低的现象被认为是 衰老大脑对缺血性损伤的“敏感”性质。老年脊髓也容易受伤。 近年来，地面水平下降导致脊髓损伤（SCI）是最常见的创伤之一 遭受急诊室的老年患者的困扰。不幸的是，我们几乎一无所知 脊髓的微血管和血液动力学如何随着年龄的增长而变化。本研究旨在解决这个问题 知识差距。我们假设在微脉管系统中有重大变化 颈椎衰老，该会议增加了受伤的脆弱性。我们的小组最近有 开发的新方法，使用强大的弹药超级对比度增强超声（CEU） 成像，以无与伦比的临时性可视化微脉管系统内的血流（每30,000帧 第二）和空间（降至50微米）分辨率。与其他成像方式的重要背道而驰， 其中仅检查了从组织表面深处几百微米的微血管流动（例如， 激光斑点和两个光子成像），超快CEUS成像使我们能够检查核内质的 脊髓组织整个深度内的微血管结构和血流血流动力学 时间。我们将应用这种创新的静脉内成像进行研究1）脊柱内微举行解剖结构和 在正常衰老期间的功能，2）与年龄相关的微血管脆弱性TSCI后。此外， 在男性和女性之间发现了脑血流和微血管密度差异 人类和啮齿动物模型。因此，将在正常衰老过程中检查微血管变化 两个性别。这项研究的结果将是理解性别和年龄相关的改变的基础 脊髓的静态和动态微血管功能。