Macaisa Carla Mari, Watabe Tadashi, Liu Yuwei, Romanov Victor, Kanai Yasukazu, Horitsugi Genki, Kato Hiroki, Shimosegawa Eku, Hatazawa Jun
Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.
Department of Molecular Imaging in Medicine, Osaka University Graduate School of Medicine,Suita 565-0871, Japan.
Brain Sci. 2019 May 3;9(5):101. doi: 10.3390/brainsci9050101.
Fluorocitrate (FC) is a specific metabolic inhibitor of the tricarboxylic acid (TCA) cycle in astrocytes. The purpose of this study was to evaluate whether inhibition of the astrocyte TCA cycle by FC would affect the oxygen metabolism in the rat brain. At 4 h after the intracranial FC injection, the rats ( = 9) were investigated by O-labeled gas PET to measure the cerebral blood flow (CBF), the cerebral metabolic rate of oxygen (CMRO), oxygen extraction fraction (OEF), and cerebral blood volume (CBV). After the O-gas PET, the rats were given an intravenous injection of C-acetate for autoradiography. O-gas PET showed no significant differences in any of the measured parameters between the ipsilateral and contralateral striatum (high dose group: CBF (54.4 ± 8.8 and 55.3 ± 11.6 mL/100mL/min), CMRO (7.0 ± 0.9 and 7.1 ± 1.2 mL/100mL/min), OEF (72.0 ± 8.9 and 70.8 ± 8.2%), and CBV (4.1 ± 0.8 and 4.2 ± 0.9 mL/100mL), respectively). In contrast, the C-acetate autoradiography revealed a significant inhibition of the astrocyte metabolism in the ipsilateral striatum. The regional cerebral oxygen consumption as well as the hemodynamic parameters were maintained even in the face of inhibition of the astrocyte TCA cycle metabolism in the rat brain.
氟柠檬酸(FC)是星形胶质细胞中三羧酸(TCA)循环的一种特异性代谢抑制剂。本研究的目的是评估FC对星形胶质细胞TCA循环的抑制是否会影响大鼠脑内的氧代谢。在颅内注射FC后4小时,对9只大鼠进行了¹⁸O标记气体PET检查,以测量脑血流量(CBF)、脑氧代谢率(CMRO₂)、氧摄取分数(OEF)和脑血容量(CBV)。¹⁸O气体PET检查后,给大鼠静脉注射¹¹C-醋酸盐进行放射自显影。¹⁸O气体PET检查显示,同侧和对侧纹状体的任何测量参数均无显著差异(高剂量组:CBF分别为(54.4±8.8和55.3±11.6 mL/100mL/min),CMRO₂分别为(7.0±0.9和7.1±1.2 mL/100mL/min),OEF分别为(72.0±8.9和70.8±8.2%),CBV分别为(4.1±0.8和4.2±0.9 mL/100mL))。相比之下,¹¹C-醋酸盐放射自显影显示同侧纹状体中星形胶质细胞代谢受到显著抑制。即使大鼠脑内星形胶质细胞TCA循环代谢受到抑制,局部脑氧消耗以及血流动力学参数仍保持稳定。