@misc{oai:repo.qst.go.jp:00071123,
 author = {Ito, Hiroshi and Takuwa, Hiroyuki and Tajima, Yousuke and Kawaguchi, Hiroshi and Masamoto, Kazuto and Taniguchi, Jyunko and Ikoma, Youko and Seki, Chie and Masanobu, Ibaraki and Kanno, Iwao and 伊藤 浩 and 田桑 弘之 and 田島 洋佑 and 川口 拓之 and 正本 和人 and 谷口 順子 and 生駒 洋子 and 関 千江 and 茨木 正信 and 菅野 巖},
 month = {May},
 note = {Objectives: According to a model for the regulation of cerebral oxygen delivery proposed by Hyder et al. [1], 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 capillary blood volume, and therefore changes in D can be estimated from changes in capillary diameter. The discrepancy between the increases in CBF and cerebral metabolic rate of oxygen (CMRO2) during neural activation and deactivation observed in crossed cerebellar diaschisis (CCD) caused by contralateral supratentorial lesions has been reported to causes a significant decrease and increase in OEF using positron emission tomography (PET) in humans, respectively [2, 3]. In the present study, changes in D during neural activation and deactivation were estimated from changes in capillary diameter measured by in vivo two-photon laser microscopic imaging in mice, and compared with those calculated from measures by PET in humans reported previously.
Methods: The cortical vasculature was imaged with two-photon laser microscope through a chronic cranial window at the somatosensory cortex and cerebellum in awake mice (C57BL/6J mice, N=4) after intraperitoneal administration of sulforhodamine 101 (10 mM, 8 muL/g) for labelling blood plasma. First, capillary vessels diameter in the somatosensory cortex was measured at baseline and during sensory stimulation (Whisker stimulation: 10Hz). Second, capillary vessels diameter in the cerebellum was measured at baseline and one day after permanent occlusion of contralateral middle cerebral artery which could cause CCD. Changes in capillary diameter during neural activation and deactivation were calculated, and then changes in D were estimated. Changes in D during neural activation and deactivation caused by motor task and CCD, respectively, were also calculated as OEF=1-exp(-D/CBF) from measures by PET in humans previously reported [2, 3].
Results: Changes in capillary diameter were 6 +- 2% and -10 +- 3%, and changes in D were 13 +- 5% and -20 +- 6% during neural activation (somatosensory cortex) and deactivation (cerebellum) in mice, respectively. Changes in CBF, CMRO2, and OEF during neural activation by motor task reported in humans were 47%, 11%, and -24%, respectively, in the primary motor cortex, and therefore change in D calculated was 7% [2]. Changes in CBF, CMRO2, and OEF during neural deactivation by CCD reported in humans were -20%, -12%, and 8%, respectively, and therefore change in D calculated was -11% [3].
Conclusions: The degree of changes in D during both neural activation and deactivation were larger in mice than in humans, however the degree of changes in D during neural activation were smaller than during neural deactivation for both mice and humans. This might indicate the validity of a model for the regulation of cerebral oxygen delivery proposed by Hyder et al. [1].
References:
[1] Hyder F, et al. J Appl Physiol 1998; 85: 554-564.
[2] Ito H, et al. J Cereb Blood Flow Metab 2005; 25: 371-377.
[3] Ito H, et al. Ann Nucl Med 2002; 16: 249-254., Brain & BrainPET 2013},
 title = {Changes in effective diffusivity for oxygen during neural activation and deactivation estimated from capillary diameter measured by two-photon laser microscope},
 year = {2013}
}