量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum Science and Technology.
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Objectives: Neural activation has been reported to cause larger increase in cerebral blood flow (CBF) than cerebral blood volume (CBV) in humans using PET [1] and has been reported to cause larger increases in red blood cell RBC velocity than RBC concentration in mice using Laser-Doppler flowmetry (LDF) [2]. Crossed cerebellar diaschisis (CCD) caused by contralateral supratentorial lesions can be considered as a condition of neural deactivation, and hemodynamic changes in CCD measured with positron emission tomography (PET) in humans have been reported to show almost the same degree of decrease in CBF and CBV [3]. In the present study, we developed a new mouse model of CCD and measured the change in RBC velocity and concentration due to CCD using LDF.
Methods: RBC velocity and concentration were measured with LDF through a chronic cranial window at the cerebellum in awake mice (C57BL/6J mice, 27-30g, N=6) riding our custom-made apparatus [4]. This apparatus consisted of a head holder and styrofoam ball float on a jet of air under the mice. This allows the mice to walk freely on the ball during LDF measurement. RBC velocity and concentration in bilateral cerebellum were measured at baseline and one day after permanent occlusion of contralateral middle cerebral artery (MCAO) which can cause CCD. The ratio of CCD side to unaffected side in cerebellum for measures by LDF was calculated.
Results: The ratio of CCD side to unaffected side in cerebellum for CBF corresponding to RBC velocity multiplied by RBC concentration after MCAO was decreased by -18% as compared to that of baseline. The ratio of CCD side to unaffected side in cerebellum for RBC concentration after MCAO was decreased by -23% as compared to that of baseline. However, no significant changes in the ratio of CCD side to unaffected side in cerebellum were observed for RBC velocity.
Discussion: The present results indicate that reduction of CBF induced by neural deactivation was mainly caused by the decrease in RBC concentration. The relationship between changes in RBC velocity and concentration due to a neural deactivation is opposite to those due to a neural activation [3]. If RBC concentration can be used as an indicator of CBV, hemodynamic changes due to neural activation and deactivation measured by LDF might be in good agreement with PET measurement in humans previously reported [1,3]. It is likely that our newly established mouse model of CCD will be useful for investigation of the effects of neural deactivation on cerebral microcirculation using two-photon laser microscope and animal PET.
References:
[1] Ito H, et al. J Cereb Blood Flow Metab 2005; 25: 371-377.
[2] Takuwa H, et al. Brain Res. 2012; 1472; 107-112
[3] Ito H, et al. Ann Nucl Med 2002; 16: 249-254.
[4] Takuwa H, et al. Brain Res. 2011; 1369; 103-111
Hemodynamic changes in crossed cerebellar diaschisis measured by Laser-Doppler flowmetry in awake mice
