Lifelong exposure to high-altitude hypoxia in humans is associated with improved redox homeostasis and structural-functional adaptations of the neurovascular unit
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Lifelong exposure to high-altitude hypoxia in humans is associated with improved redox homeostasis and structural-functional adaptations of the neurovascular unit. / Stacey, Benjamin S; Hoiland, Ryan L; Caldwell, Hannah Grace; Howe, Connor A; Vermeulen, Tyler; Tymko, Michael M; Vizcardo-Galindo, Gustavo A; Bermudez, Daniella; Figueroa-Mujíica, Rómulo J; Gasho, Christopher; Tuaillon, Edouard; Hirtz, Christophe; Lehmann, Sylvain; Marchi, Nicola; Tsukamoto, Hayato; Villafuerte, Francisco C; Ainslie, Philip N; Bailey, Damian M.
In: Journal of Physiology, Vol. 601, No. 6, 2023, p. 1095-1120.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Lifelong exposure to high-altitude hypoxia in humans is associated with improved redox homeostasis and structural-functional adaptations of the neurovascular unit
AU - Stacey, Benjamin S
AU - Hoiland, Ryan L
AU - Caldwell, Hannah Grace
AU - Howe, Connor A
AU - Vermeulen, Tyler
AU - Tymko, Michael M
AU - Vizcardo-Galindo, Gustavo A
AU - Bermudez, Daniella
AU - Figueroa-Mujíica, Rómulo J
AU - Gasho, Christopher
AU - Tuaillon, Edouard
AU - Hirtz, Christophe
AU - Lehmann, Sylvain
AU - Marchi, Nicola
AU - Tsukamoto, Hayato
AU - Villafuerte, Francisco C
AU - Ainslie, Philip N
AU - Bailey, Damian M
N1 - This article is protected by copyright. All rights reserved.
PY - 2023
Y1 - 2023
N2 - High-altitude (HA) hypoxia may alter the structural–functional integrity of the neurovascular unit (NVU). Herein, we compared male lowlanders (n = 9) at sea level (SL) and after 14 days acclimatization to 4300 m (chronic HA) in Cerro de Pasco (CdP), Péru (HA), against sex-, age- and body mass index-matched healthy highlanders (n = 9) native to CdP (lifelong HA). Venous blood was assayed for serum proteins reflecting NVU integrity, in addition to free radicals and nitric oxide (NO). Regional cerebral blood flow (CBF) was examined in conjunction with cerebral substrate delivery, dynamic cerebral autoregulation (dCA), cerebrovascular reactivity to carbon dioxide (CVRCO2) and neurovascular coupling (NVC). Psychomotor tests were employed to examine cognitive function. Compared to lowlanders at SL, highlanders exhibited elevated basal plasma and red blood cell NO bioavailability, improved anterior and posterior dCA, elevated anterior CVRCO2 and preserved cerebral substrate delivery, NVC and cognition. In highlanders, S100B, neurofilament light-chain (NF-L) and T-tau were consistently lower and cognition comparable to lowlanders following chronic-HA. These findings highlight novel integrated adaptations towards regulation of the NVU in highlanders that may represent a neuroprotective phenotype underpinning successful adaptation to the lifelong stress of HA hypoxia.
AB - High-altitude (HA) hypoxia may alter the structural–functional integrity of the neurovascular unit (NVU). Herein, we compared male lowlanders (n = 9) at sea level (SL) and after 14 days acclimatization to 4300 m (chronic HA) in Cerro de Pasco (CdP), Péru (HA), against sex-, age- and body mass index-matched healthy highlanders (n = 9) native to CdP (lifelong HA). Venous blood was assayed for serum proteins reflecting NVU integrity, in addition to free radicals and nitric oxide (NO). Regional cerebral blood flow (CBF) was examined in conjunction with cerebral substrate delivery, dynamic cerebral autoregulation (dCA), cerebrovascular reactivity to carbon dioxide (CVRCO2) and neurovascular coupling (NVC). Psychomotor tests were employed to examine cognitive function. Compared to lowlanders at SL, highlanders exhibited elevated basal plasma and red blood cell NO bioavailability, improved anterior and posterior dCA, elevated anterior CVRCO2 and preserved cerebral substrate delivery, NVC and cognition. In highlanders, S100B, neurofilament light-chain (NF-L) and T-tau were consistently lower and cognition comparable to lowlanders following chronic-HA. These findings highlight novel integrated adaptations towards regulation of the NVU in highlanders that may represent a neuroprotective phenotype underpinning successful adaptation to the lifelong stress of HA hypoxia.
KW - Faculty of Science
KW - Acclimatization
KW - Cerebrovascular function
KW - Cognition
KW - Free radicals
KW - High-altitude
KW - Neurovascular unit
U2 - 10.1113/JP283362
DO - 10.1113/JP283362
M3 - Journal article
C2 - 36633375
VL - 601
SP - 1095
EP - 1120
JO - The Journal of Physiology
JF - The Journal of Physiology
SN - 0022-3751
IS - 6
ER -
ID: 333480022