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 journalJournal articleResearchpeer-review

  • Benjamin S Stacey
  • Ryan L Hoiland
  • Caldwell, Hannah Grace
  • Connor A Howe
  • Tyler Vermeulen
  • Michael M Tymko
  • Gustavo A Vizcardo-Galindo
  • Daniella Bermudez
  • Rómulo J Figueroa-Mujíica
  • Christopher Gasho
  • Edouard Tuaillon
  • Christophe Hirtz
  • Sylvain Lehmann
  • Nicola Marchi
  • Hayato Tsukamoto
  • Francisco C Villafuerte
  • Philip N Ainslie
  • Damian M Bailey
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.
Original languageEnglish
JournalJournal of Physiology
Issue number6
Pages (from-to)1095-1120
Number of pages26
Publication statusPublished - 2023
Externally publishedYes

Bibliographical note

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    Research areas

  • Faculty of Science - Acclimatization, Cerebrovascular function, Cognition, Free radicals, High-altitude, Neurovascular unit

ID: 333480022