Defining microvascular structure and function in the aged cervical spinal cord

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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.