Key to the understanding of the principles of physiological and structural acclimatization to changes in the balance between energy supply (represented by substrate and oxygen delivery, and mitochondrial oxidative phosphorylation) and energy demand (initiated by neuronal activity) is to determine the controlling variables, how they are sensed and the mechanisms initiated to maintain the balance. The mammalian brain depends completely on continuous delivery of oxygen to maintain its function. We hypothesized that tissue oxygen is the primary sensed variable. In this study two-photon phosphorescence lifetime microscopy (2PLM) was used to determine and define the tissue oxygen tension field within the cerebral cortex of mice to a cortical depth of between 200–250 μm under normoxia and acute hypoxia (FiO2 = 0.10). High-resolution images can provide quantitative distributions of oxygen and intercapillary oxygen gradients. The data are best appreciated by quantifying the distribution histogram that can then be used for analysis. For example, in the brain cortex of a mouse, at a depth of 200 μm, tissue oxygen tension was mapped and the distribution histogram was compared under normoxic and mild hypoxic conditions. This powerful method can provide for the first time a description of the delivery and availability of brain oxygen in vivo.
Oxygen partial pressure 2PLM Tissue oxygen tension Distribution histogram Mouse
This is a preview of subscription content, log in to check access.
This study was supported by the NIH grants R01 NS38632, R24 NS092986, R01 NS091230, R01 NS055104, and R01 EB021018.
LaManna JC, Vendel LM, Farrell RM (1992) Brain adaptation to chronic hypobaric hypoxia in rats. J Appl Physiol 72:2238–2243PubMedGoogle Scholar
LaManna JC, Cordisco BR, Knuese DE et al (1994) Increased capillary segment length in cerebral cortical microvessels of rats exposed to 3 weeks of hypobaric hypoxia. Adv Exp Med Biol 345:627–632CrossRefPubMedGoogle Scholar
Ndubuizu O, LaManna JC (2007) Brain tissue oxygen concentration measurements. Antioxid Redox Signal 9(8):1207–1219CrossRefPubMedGoogle Scholar
Sakadžić S, Roussakis E, Yaseen MA et al (2010) Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue. Nat Methods 7(9):755–759CrossRefPubMedPubMedCentralGoogle Scholar
Sakadžić S, Mandeville ET, Gagnon L et al (2014) Large arteriolar component of oxygen delivery implies a safe margin of oxygen supply to cerebral tissue. Nat Commun 5:5734CrossRefPubMedPubMedCentralGoogle Scholar
Baraghis E, Devor A, Fang Q et al (2011) Two-photon microscopy of cortical NADH fluorescence intensity changes: correcting contamination from the hemodynamic response. J Biomed Opt 16(10):106003CrossRefPubMedPubMedCentralGoogle Scholar
Lauro KL, LaManna JC (1997) Adequacy of cerebral vascular remodeling following three weeks of hypobaric hypoxia. Examined by an integrated composite analytical model. Adv Exp Med Biol 411:369–376CrossRefPubMedGoogle Scholar
Dunn JF, Grinberg O, Roche M et al (2000) Noninvasive assessment of cerebral oxygenation during acclimation to hypobaric hypoxia. J Cereb Blood Flow Metab 20(12):1632–1635CrossRefPubMedGoogle Scholar