Exploiting moderate hypoxia to benefit patients with brain disease: Molecular mechanisms and translational research in progress  

作　　者：Hannelore Ehrenreich Max Gassmann Luise Poustka Martin Burtscher Peter Hammermann PhD Anna-Leena Sirén Klaus-Armin Nave Kamilla Miskowiak 

机构地区：[1]Clinical Neuroscience,Max Planck Institute for Multidisciplinary Sciences,Göttingen,Germany [2]Institute of Veterinary Physiology and Zürich Center for Integrative Human Physiology,University of Zürich,Zürich,Switzerland [3]Department of Child and Adolescent Psychiatry and Psychotherapy,University Medical Center Göttingen,Göttingen,Germany [4]Faculty of Sports Science,University of Innsbruck,Innsbruck,Austria [5]HBL Investmentpartners GmbH,München‐Frankfurt,Germany [6]Departments of Neurophysiology and Neurosurgery,University of Würzburg,Würzburg,Germany [7]Department of Neurogenetics,Max Planck Institute for Multidisciplinary Sciences,Göttingen,Germany [8]Psychiatric Centre,Copenhagen University Hospital,Rigshospitalet,Copenhagen,Denmark [9]Department of Psychology,University of Copenhagen,Copenhagen,Denmark

出　　处：《Neuroprotection》2023年第1期9-19,共11页神经保护（英文）

基　　金：supported by the Max Planck Society,the Max Planck Förderstiftung,the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation),via DFG-Center for Nanoscale Microscopy&Molecular Physiology of the Brain(CNMPB)and DFG-TRR 274/12020–408885537.

摘　　要：Hypoxia is increasingly recognized as an important physiological driving force.A specific transcriptional program,induced by a decrease in oxygen(O2)availability,for example,inspiratory hypoxia at high altitude,allows cells to adapt to lower O2 and limited energy metabolism.This transcriptional program is partly controlled by and partly independent of hypoxia-inducible factors.Remarkably,this same transcriptional program is stimulated in the brain by extensive motor-cognitive exercise,leading to a relative decrease in O2 supply,compared to the acutely augmented O2 requirement.We have coined the term“functional hypoxia”for this important demand-responsive,relative reduction in O2 availability.Functional hypoxia seems to be critical for enduring adaptation to higher physiological challenge that includes substantial“brain hardware upgrade,”underlying advanced performance.Hypoxia-induced erythropoietin expression in the brain likely plays a decisive role in these processes,which can be imitated by recombinant human erythropoietin treatment.This article review presents hints of how inspiratory O2 manipulations can potentially contribute to enhanced brain function.It thereby provides the ground for exploiting moderate inspiratory plus functional hypoxia to treat individuals with brain disease.Finally,it sketches a planned multistep pilot study in healthy volunteers and first patients,about to start,aiming at improved performance upon motor-cognitive training under inspiratory hypoxia.

关 键 词：brain EPO circle ERYTHROPOIETIN functional hypoxia HIF human pilot study HYPEROXIA inspiratory oxygen manipulations motor-cognitive performance PBMC translation 

分 类 号：R741[医药卫生—神经病学与精神病学]