Gareau Daniel S, RochaKim Nicholas, Choudhury Arnab, Bamkole Michael, Snuderl Matija, Zou Julia, Yaroslavsky Anna, Jacques Steven L, Strickland Sidney, Krueger James G, Ahn Hyung Jin
Laboratory of Investigative Dermatology, The Rockefeller University, New York, NY, United States.
Department of Pharmacology, Physiology and Neuroscience, Rutgers-New Jersey Medical School, Newark, NJ, United States.
Front Mol Neurosci. 2023 Jul 3;16:1163447. doi: 10.3389/fnmol.2023.1163447. eCollection 2023.
Many Alzheimer's disease (AD) patients suffer from altered cerebral blood flow and damaged cerebral vasculature. Cerebrovascular dysfunction could play an important role in this disease. However, the mechanism underlying a vascular contribution in AD is still unclear. Cerebrovascular reactivity (CVR) is a critical mechanism that maintains cerebral blood flow and brain homeostasis. Most current methods to analyze CVR require anesthesia which is known to hamper the investigation of molecular mechanisms underlying CVR. We therefore combined spectroscopy, spectral analysis software, and an implantable device to measure cerebral blood volume fraction () and oxygen saturation () in unanesthetized, freely-moving mice. Then, we analyzed basal and and CVR of 5-month-old C57BL/6 mice during hypercapnia as well as during basic behavior such as grooming, walking and running. Moreover, we analyzed the CVR of freely-moving AD mice and their wildtype (WT) littermates during hypercapnia and could find impaired CVR in AD mice compared to WT littermates. Our results suggest that this optomechanical approach to reproducibly getting light into the brain enabled us to successfully measure CVR in unanesthetized freely-moving mice and to find impaired CVR in a mouse model of AD.
许多阿尔茨海默病（AD）患者存在脑血流改变和脑血管受损的情况。脑血管功能障碍可能在这种疾病中起重要作用。然而，AD中血管因素的潜在机制仍不清楚。脑血管反应性（CVR）是维持脑血流和脑内环境稳定的关键机制。目前大多数分析CVR的方法都需要麻醉，而麻醉已知会妨碍对CVR潜在分子机制的研究。因此，我们将光谱学、光谱分析软件和一种可植入装置相结合，以测量未麻醉、自由活动小鼠的脑血容量分数（ ）和血氧饱和度（ ）。然后，我们分析了5月龄C57BL/6小鼠在高碳酸血症期间以及梳理毛发、行走和奔跑等基本行为过程中的基础 和 以及CVR。此外，我们分析了自由活动的AD小鼠及其野生型（WT）同窝小鼠在高碳酸血症期间的CVR，发现与WT同窝小鼠相比，AD小鼠的CVR受损。我们的结果表明，这种可重复地将光导入大脑的光机械方法使我们能够成功测量未麻醉自由活动小鼠的CVR，并在AD小鼠模型中发现CVR受损。
