한빛사논문
Hannah C. Bennett 1,7, Qingguang Zhang 2,3,7, Yuan-ting Wu 1,5,7, Steffy B. Manjila 1,7, Uree Chon 1,6, Donghui Shin 1, Daniel J. Vanselow 1, Hyun-Jae Pi 1, Patrick J. Drew 2,4 & Yongsoo Kim 1,2,*
1Department of Neural and Behavioral Sciences, The Pennsylvania State University, Hershey, PA 17033, USA.
2Center for Neural Engineering, Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA 16802, USA.
3Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
4Department of Biomedical Engineering, Biology, and Neurosurgery, The Pennsylvania State University, University Park, PA 16802, USA.
5Present address: Department of Neurosurgery, Department of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
6Present address: Neurosciences Graduate Program, Stanford University, Stanford, CA 94305, USA.
7These authors contributed equally: Hannah C. Bennett, Qingguang Zhang, Yuan-ting Wu, Steffy B. Manjila.
*Corresponding author: correspondence to Yongsoo Kim
Abstract
Aging is frequently associated with compromised cerebrovasculature and pericytes. However, we do not know how normal aging differentially impacts vascular structure and function in different brain areas. Here we utilize mesoscale microscopy methods and in vivo imaging to determine detailed changes in aged murine cerebrovascular networks. Whole-brain vascular tracing shows an overall ~10% decrease in vascular length and branching density with ~7% increase in vascular radii in aged brains. Light sheet imaging with 3D immunolabeling reveals increased arteriole tortuosity of aged brains. Notably, vasculature and pericyte densities show selective and significant reductions in the deep cortical layers, hippocampal network, and basal forebrain areas. We find increased blood extravasation, implying compromised blood-brain barrier function in aged brains. Moreover, in vivo imaging in awake mice demonstrates reduced baseline and on-demand blood oxygenation despite relatively intact neurovascular coupling. Collectively, we uncover regional vulnerabilities of cerebrovascular network and physiological changes that can mediate cognitive decline in normal aging.
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