Fiberoptic hemodynamic spectroscopy reveals abnormal cerebrovascular reactivity in a freely moving mouse model of Alzheimer's disease.

Fiberoptic hemodynamic spectroscopy reveals abnormal cerebrovascular reactivity in a freely moving mouse model of Alzheimer's disease.
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DOI:
10.3389/fnmol.2023.1163447
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发表时间:
2023
影响因子:
4.8
通讯作者:
Ahn, Hyung Jin
Ahn, Hyung Jin
中科院分区:
医学2区
文献类型:
--
作者:
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

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许多阿尔茨海默病(AD)患者患有改变的脑血流和受损的脑血管。脑血管功能障碍在本病中可能起重要作用。然而,血管在AD中的作用机制仍不清楚。脑血管反应性(CVR)是维持脑血流和脑内环境稳定的重要机制。目前大多数分析CVR的方法需要麻醉,这是已知的,阻碍了CVR的分子机制的调查。因此,我们结合光谱,光谱分析软件,和植入式设备来测量脑血容量分数(CBVF)和氧饱和度(SO2)在未麻醉,自由移动的小鼠。然后,我们分析了5个月大的C57 BL/6小鼠在高碳酸血症期间以及在梳理、行走和跑步等基本行为期间的基础CBVF和SO2以及CVR。此外,我们分析了高碳酸血症期间自由移动的AD小鼠及其野生型(WT)同窝仔的CVR,并发现与WT同窝仔相比,AD小鼠的CVR受损。我们的研究结果表明,这种可重复地将光引入大脑的光机械方法使我们能够成功地测量未麻醉自由移动小鼠的CVR,并在AD小鼠模型中发现受损的CVR。
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 (CBVF) and oxygen saturation (SO2) in unanesthetized, freely-moving mice. Then, we analyzed basal CBVF and SO2, 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.
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