Impaired dynamics of precapillary sphincters and pericytes at first-order capillaries predict reduced neurovascular function in the aging mouse brain
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The microvascular inflow tract, comprising the penetrating arterioles, precapillary sphincters and first-order capillaries, is the bottleneck for brain blood flow and energy supply. Exactly how aging alters the structure and function of the microvascular inflow tract remains unclear. By in vivo four-dimensional two-photon imaging, we reveal an age-dependent decrease in vaso-responsivity accompanied by a decrease in vessel density close to the arterioles and loss of vascular mural cell processes, although the number of mural cell somas and their alpha smooth muscle actin density were preserved. The age-related reduction in vascular reactivity was mostly pronounced at precapillary sphincters, highlighting their crucial role in capillary blood flow regulation. Mathematical modeling revealed impaired pressure and flow control in aged mice during vasoconstriction. Interventions that preserve dynamics of cerebral blood vessels may ameliorate age-related decreases in blood flow and prevent brain frailty.
|Status||Udgivet - 2023|
We acknowledge Niels Bohr Institute Electronics & Mechanical Workshop, University of Copenhagen, where we receive great technical support from S. Stausgaard-Petersen, J. H. Fagerlund and their colleagues. We acknowledge the Core Facility for Integrated Microscopy, Faculty of Health and Medical Sciences, University of Copenhagen, where we used spinning disc confocal microscopy in our in vitro studies. This study was supported by the Lundbeck Foundation (R273-2017-1791 and R345-2020-1440), the Danish Medical Research Council (1133-00016A), the Alice Brenaa Foundation, Augustinus Foundation (19-2858), Carl og Ellen Hertz Familielegat (19.19.2), A. P. Møller Foundation (20-L-0243), Helsefonden (21-B-0441), the Novo Nordisk foundation (0064289) and a Nordea Foundation Grant to the Center for Healthy Aging (02-2017-1749).
© 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.