Impaired dynamics of precapillary sphincters and pericytes at first-order capillaries predict reduced neurovascular function in the aging mouse brain
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Impaired dynamics of precapillary sphincters and pericytes at first-order capillaries predict reduced neurovascular function in the aging mouse brain. / Cai, Changsi; Zambach, Stefan Andreas; Grubb, Søren; Tao, Lechan; He, Chen; Lind, Barbara Lykke; Thomsen, Kirsten Joan; Zhang, Xiao; Hald, Bjørn Olav; Nielsen, Reena Murmu; Kim, Kayeon; Devor, Anna; Lønstrup, Micael; Lauritzen, Martin Johannes.
In: Nature Aging, Vol. 3, 2023, p. 173-184.Research output: Contribution to journal › Letter › Research › peer-review
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TY - JOUR
T1 - Impaired dynamics of precapillary sphincters and pericytes at first-order capillaries predict reduced neurovascular function in the aging mouse brain
AU - Cai, Changsi
AU - Zambach, Stefan Andreas
AU - Grubb, Søren
AU - Tao, Lechan
AU - He, Chen
AU - Lind, Barbara Lykke
AU - Thomsen, Kirsten Joan
AU - Zhang, Xiao
AU - Hald, Bjørn Olav
AU - Nielsen, Reena Murmu
AU - Kim, Kayeon
AU - Devor, Anna
AU - Lønstrup, Micael
AU - Lauritzen, Martin Johannes
N1 - Publisher Copyright: © 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.1038/s43587-022-00354-1
DO - 10.1038/s43587-022-00354-1
M3 - Letter
C2 - 37118115
AN - SCOPUS:85146884202
VL - 3
SP - 173
EP - 184
JO - Nature Aging
JF - Nature Aging
SN - 2662-8465
ER -
ID: 334910688