The Journal of Physiological Sciences

, Volume 67, Issue 2, pp 325–330 | Cite as

Changes in effective diffusivity for oxygen during neural activation and deactivation estimated from capillary diameter measured by two-photon laser microscope

  • Hiroshi Ito
  • Hiroyuki Takuwa
  • Yosuke Tajima
  • Hiroshi Kawaguchi
  • Takuya Urushihata
  • Junko Taniguchi
  • Yoko Ikoma
  • Chie Seki
  • Masanobu Ibaraki
  • Kazuto Masamoto
  • Iwao Kanno
Original Paper

Abstract

The relation between cerebral blood flow (CBF) and cerebral oxygen extraction fraction (OEF) can be expressed using the effective diffusivity for oxygen in the capillary bed (D) as OEF = 1 − exp(−D/CBF). The D value is proportional to the microvessel blood volume. In this study, changes in D during neural activation and deactivation were estimated from changes in capillary and arteriole diameter measured by two-photon microscopy in awake mice. Capillary and arteriole vessel diameter in the somatosensory cortex and cerebellum were measured under neural activation (sensory stimulation) and neural deactivation [crossed cerebellar diaschisis (CCD)], respectively. Percentage changes in D during sensory stimulation and CCD were 10.3 ± 7.3 and −17.5 ± 5.3 % for capillary diameter of <6 μm, respectively. These values were closest to the percentage changes in D calculated from previously reported human positron emission tomography data. This may indicate that thinner capillaries might play the greatest role in oxygen transport from blood to brain tissue.

Keywords

Brain imaging Capillary Cerebral blood flow PET Two-photon laser microscope 

References

  1. 1.
    Hyder F, Shulman RG, Rothman DL (1998) A model for the regulation of cerebral oxygen delivery. J Appl Physiol 85:554–564PubMedGoogle Scholar
  2. 2.
    Takuwa H, Masamoto K, Yamazaki K, Kawaguchi H, Ikoma Y, Tajima Y et al (2013) Long-term adaptation of cerebral hemodynamic response to somatosensory stimulation during chronic hypoxia in awake mice. J Cereb Blood Flow Metab 33:774–779CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Tajima Y, Takuwa H, Kokuryo D, Kawaguchi H, Seki C, Masamoto K et al (2014) Changes in cortical microvasculature during misery perfusion measured by two-photon laser scanning microscopy. J Cereb Blood Flow Metab 34:1363–1372CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Masamoto K, Tanishita K (2009) Oxygen transport in brain tissue. J Biomech Eng 131:074002CrossRefPubMedGoogle Scholar
  5. 5.
    Safaeian N, David T (2013) A computational model of oxygen transport in the cerebrocapillary levels for normal and pathologic brain function. J Cereb Blood Flow Metab 33:1633–1641CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Fox PT, Raichle ME (1986) Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. Proc Natl Acad Sci USA 83:1140–1144CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Seitz RJ, Roland PE (1992) Vibratory stimulation increases and decreases the regional cerebral blood flow and oxidative metabolism: a positron emission tomography (PET) study. Acta Neurol Scand 86:60–67CrossRefPubMedGoogle Scholar
  8. 8.
    Vafaee MS, Gjedde A (2000) Model of blood–brain transfer of oxygen explains nonlinear flow-metabolism coupling during stimulation of visual cortex. J Cereb Blood Flow Metab 20:747–754CrossRefPubMedGoogle Scholar
  9. 9.
    Ito H, Kanno I, Shimosegawa E, Tamura H, Okane K, Hatazawa J (2002) Hemodynamic changes during neural deactivation in human brain: a positron emission tomography study of crossed cerebellar diaschisis. Ann Nucl Med 16:249–254CrossRefPubMedGoogle Scholar
  10. 10.
    Ito H, Ibaraki M, Kanno I, Fukuda H, Miura S (2005) Changes in cerebral blood flow and cerebral oxygen metabolism during neural activation measured by positron emission tomography: comparison with blood oxygenation level-dependent contrast measured by functional magnetic resonance imaging. J Cereb Blood Flow Metab 25:371–377CrossRefPubMedGoogle Scholar
  11. 11.
    Takuwa H, Autio J, Nakayama H, Matsuura T, Obata T, Okada E et al (2011) Reproducibility and variance of a stimulation-induced hemodynamic response in barrel cortex of awake behaving mice. Brain Res 1369:103–111CrossRefPubMedGoogle Scholar
  12. 12.
    Takuwa H, Matsuura T, Obata T, Kawaguchi H, Kanno I, Ito H (2012) Hemodynamic changes during somatosensory stimulation in awake and isoflurane-anesthetized mice measured by laser-Doppler flowmetry. Brain Res 1472:107–112CrossRefPubMedGoogle Scholar
  13. 13.
    Takuwa H, Tajima Y, Kokuryo D, Matsuura T, Kawaguchi H, Masamoto K et al (2013) Hemodynamic changes during neural deactivation in awake mice: a measurement by laser-Doppler flowmetry in crossed cerebellar diaschisis. Brain Res 1537:350–355CrossRefPubMedGoogle Scholar
  14. 14.
    Tomita Y, Kubis N, Calando Y, Tran Dinh A, Meric P, Seylaz J et al (2005) Long-term in vivo investigation of mouse cerebral microcirculation by fluorescence confocal microscopy in the area of focal ischemia. J Cereb Blood Flow Metab 25:858–867CrossRefPubMedGoogle Scholar
  15. 15.
    Park SH, Masamoto K, Hendrich K, Kanno I, Kim SG (2008) Imaging brain vasculature with BOLD microscopy: MR detection limits determined by in vivo two-photon microscopy. Magn Reson Med 59:855–865CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Sekiguchi Y, Masamoto K, Takuwa H, Kawaguchi H, Kanno I, Ito H et al (2013) Measuring the vascular diameter of brain surface and parenchymal arteries in awake mouse. Adv Exp Med Biol 789:419–425CrossRefPubMedGoogle Scholar
  17. 17.
    Hill RA, Tong L, Yuan P, Murikinati S, Gupta S, Grutzendler J (2015) Regional blood flow in the normal and ischemic brain is controlled by arteriolar smooth muscle cell contractility and not by capillary pericytes. Neuron 87:95–110CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Tamura A, Graham DI, McCulloch J, Teasdale GM (1981) Focal cerebral ischaemia in the rat: 1. Description of technique and early neuropathological consequences following middle cerebral artery occlusion. J Cereb Blood Flow Metab 1:53–60CrossRefPubMedGoogle Scholar
  19. 19.
    Hudetz AG (1997) Blood flow in the cerebral capillary network: a review emphasizing observations with intravital microscopy. Microcirculation 4:233–252CrossRefPubMedGoogle Scholar
  20. 20.
    Jespersen SN, Ostergaard L (2012) The roles of cerebral blood flow, capillary transit time heterogeneity, and oxygen tension in brain oxygenation and metabolism. J Cereb Blood Flow Metab 32:264–277CrossRefPubMedGoogle Scholar
  21. 21.
    Engstrom KG, Taljedal IB (1987) Altered shape and size of red blood cells in obese hyperglycaemic mice. Acta Physiol Scand 130:535–543CrossRefPubMedGoogle Scholar
  22. 22.
    Vovenko E (1999) Distribution of oxygen tension on the surface of arterioles, capillaries and venules of brain cortex and in tissue in normoxia: an experimental study on rats. European journal of physiology 437:617–623CrossRefPubMedGoogle Scholar
  23. 23.
    Itoh Y, Suzuki N (2012) Control of brain capillary blood flow. J Cereb Blood Flow Metab 32:1167–1176CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Peppiatt CM, Howarth C, Mobbs P, Attwell D (2006) Bidirectional control of CNS capillary diameter by pericytes. Nature 443:700–704CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Hamilton NB, Attwell D, Hall CN (2010) Pericyte-mediated regulation of capillary diameter: a component of neurovascular coupling in health and disease. Front Neuroenerg 21:2Google Scholar
  26. 26.
    Schulte ML, Wood JD, Hudetz AG (2003) Cortical electrical stimulation alters erythrocyte perfusion pattern in the cerebral capillary network of the rat. Brain Res 963:81–92CrossRefPubMedGoogle Scholar
  27. 27.
    Kuschinsky W, Paulson OB (1992) Capillary circulation in the brain. Cerebrovasc Brain Metab Rev 4:261–286PubMedGoogle Scholar
  28. 28.
    Hayashi T, Watabe H, Kudomi N, Kim KM, Enmi J, Hayashida K et al (2003) A theoretical model of oxygen delivery and metabolism for physiologic interpretation of quantitative cerebral blood flow and metabolic rate of oxygen. J Cereb Blood Flow Metab 23:1314–1323CrossRefPubMedGoogle Scholar
  29. 29.
    Herman P, Sanganahalli BG, Hyder F (2009) Multimodal measurements of blood plasma and red blood cell volumes during functional brain activation. J Cereb Blood Flow Metab 29:19–24CrossRefPubMedGoogle Scholar

Copyright information

© The Physiological Society of Japan and Springer Japan 2016

Authors and Affiliations

  • Hiroshi Ito
    • 1
    • 2
  • Hiroyuki Takuwa
    • 1
  • Yosuke Tajima
    • 1
  • Hiroshi Kawaguchi
    • 1
    • 3
  • Takuya Urushihata
    • 1
  • Junko Taniguchi
    • 1
  • Yoko Ikoma
    • 1
  • Chie Seki
    • 1
  • Masanobu Ibaraki
    • 4
  • Kazuto Masamoto
    • 1
    • 5
  • Iwao Kanno
    • 1
  1. 1.Biophysics Program, Molecular Imaging CenterNational Institute of Radiological SciencesChibaJapan
  2. 2.Advanced Clinical Research CenterFukushima Medical UniversityFukushimaJapan
  3. 3.Human Informatics Research InstituteNational Institute of Advanced Industrial Science and TechnologyTsukubaJapan
  4. 4.Department of Radiology and Nuclear MedicineAkita Research Institute of Brain and Blood VesselsAkitaJapan
  5. 5.Center for Frontier Science and EngineeringUniversity of Electro-CommunicationsChofuJapan

Personalised recommendations