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Lifelong exposure to high‐altitude hypoxia in humans is associated with improved redox homeostasis and structural‐functional adaptations of the neurovascular unit

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  • معلومة اضافية
    • Contributors:
      University of South Wales (USW); University of British Columbia (UBC); University of Alberta; Universidad Peruana Cayetano Heredia (UPCH); Loma Linda University; Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier); Pathogenesis and Control of Chronic and Emerging Infections (PCCEI); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Etablissement français du don du sang Montpellier -Université de Montpellier (UM); Université de Montpellier (UM); Institut des Neurosciences de Montpellier (INM); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM); Institut de Génomique Fonctionnelle (IGF); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM); Ritsumeikan University
    • بيانات النشر:
      HAL CCSD
      Wiley
    • الموضوع:
      2023
    • Collection:
      Université de Montpellier: HAL
    • نبذة مختصرة :
      International audience ; 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 4,300 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). Serum proteins were examined to reflect NVU integrity and venous blood assayed for 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 plasma and red blood cell NO bioavailability (P = 0.005, d = 1.549 and P = 0.003, d = 1.681), improved anterior and posterior dCA (low frequency Gain: P = 0.029, d = -1.292 and P = 0.017, d = -1.255 respectively), elevated anterior CVRCO2 (P = 0.113, d = -0.852) and preserved cerebral substrate delivery and NVC (all P = >0.100). In highlanders, S100B, neurofilament light-chain and T-tau were consistently lower (P = 0.018, d = -1.244, P = 0.037, d = -1.075 and P = <0.001, d = -3.894, respectively) and cognition comparable (all P = >0.100) 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. Abstract figure legend We determined how the hypoxia of high-altitude across the temporal continuum of chronic through to lifelong exposure impacts the neurovascular unit (NVU) phenotype and to what extent this is subject to altered redox homeostasis. Basal multimodal biomarkers reflecting NVU structure-function were determined in lowlanders at sea-level (lifelong normoxia) and ...
    • Relation:
      info:eu-repo/semantics/altIdentifier/pmid/36633375; PUBMED: 36633375
    • الرقم المعرف:
      10.1113/JP283362
    • الدخول الالكتروني :
      https://hal.science/hal-03946525
      https://hal.science/hal-03946525v1/document
      https://hal.science/hal-03946525v1/file/TJP-601-1095.pdf
      https://doi.org/10.1113/JP283362
    • Rights:
      http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess
    • الرقم المعرف:
      edsbas.85DC3947