Preserved Cerebral Oxygen Metabolism in Astrocytic Dysfunction: A Combination Study of 15O-Gas PET with 14C-Acetate Autoradiography
Preserved Cerebral Oxygen Metabolism in Astrocytic Dysfunction: A Combination Study of 15O-Gas PET with 14C-Acetate Autoradiography
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DOI：
10.3390/brainsci9050101
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发表时间：
2019-05-01
期刊：
影响因子：
3.3
通讯作者：
Hatazawa, Jun
中科院分区：
文献类型：
--
作者：
Macaisa, Carla Mari;Watabe, Tadashi;Hatazawa, Jun
氟柠檬酸盐（FC）是星形胶质细胞三羧酸（TCA）循环的特异性代谢抑制剂。本研究的目的是评价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 h，采用O-15标记气体PET检测大鼠脑血流量（CBF）、脑氧代谢率（CMRO 2）、氧摄取分数（OEF）和脑血容量（CBV）。在O-15-gas PET之后，给予大鼠静脉注射C-14-acetate用于放射自显影。O-15-gas PET显示同侧和对侧纹状体之间的任何测量参数均无显著差异（高剂量组：CBF（54.4 +/- 8.8和55.3 +/- 11.6 mL/100 mL/min），CMRO2（分别为7.0 ± 0.9和7.1 ± 1.2 mL/100 mL/min）、OEF（72.0 ± 8.9和70.8 ± 8.2%）和CBV（4.1 ± 0.8和4.2 ± 0.9 mL/100 mL））。相反，C-14-乙酸放射自显影显示同侧纹状体星形胶质细胞代谢的显着抑制。即使在大鼠脑中星形胶质细胞TCA循环代谢受到抑制的情况下，局部脑耗氧量和血流动力学参数仍保持不变。
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 (n = 9) were investigated by O-15-labeled gas PET to measure the cerebral blood flow (CBF), the cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral blood volume (CBV). After the O-15-gas PET, the rats were given an intravenous injection of C-14-acetate for autoradiography. O-15-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/100 mL/min), CMRO2 (7.0 +/- 0.9 and 7.1 +/- 1.2 mL/100 mL/min), OEF (72.0 +/- 8.9 and 70.8 +/- 8.2%), and CBV (4.1 +/- 0.8 and 4.2 +/- 0.9 mL/100 mL), respectively). In contrast, the C-14-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.