Slais Karel, Vorisek Ivan, Zoremba Norbert, Homola Ales, Dmytrenko Lesia, Sykova Eva
Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Exp Neurol. 2008 Jan;209(1):145-54. doi: 10.1016/j.expneurol.2007.09.008. Epub 2007 Sep 20.
The real-time iontophoretic method using tetramethylammonium-selective microelectrodes and diffusion-weighted magnetic resonance imaging were used to measure the extracellular space volume fraction alpha, tortuosity lambda and apparent diffusion coefficient of water (ADC(W)) 240 min after the administration of pilocarpine in urethane-anaesthetized rats. The obtained data were correlated with extracellular lactate, glucose, and glutamate concentrations and the lactate/pyruvate-ratio, determined by intracerebral microdialysis. The control values of alpha and lambda were 0.19+/-0.004 and 1.58+/-0.01, respectively. Following pilocarpine application, alpha decreased to 0.134+/-0.012 100 min later. Thereafter alpha increased, reaching 0.176+/-0.009 140 min later. No significant changes in lambda were observed during the entire time course of the experiment. ADC(W) was significantly decreased 100 min after pilocarpine application (549+/-8 microm(2) s(-1)) compared to controls (603+/-11 microm(2) s(-1)); by the end of the experiments, ADC(W) had returned to control values. The basal cortical levels of lactate, the lactate/pyruvate ratio, glucose and glutamate were 0.61+/-0.05 mmol/l, 33.16+/-4.26, 2.42+/-0.13 mmol/l and 6.55+/-1.31 micromol/l. Pilocarpine application led to a rise in lactate, the lactate/pyruvate ratio and glutamate levels, reaching 2.92+/-0.60 mmol/l, 84.80+/-11.72 and 22.39+/-5.85 micromol/l within about 100 min, with a subsequent decrease to control values 140 min later. The time course of changes in glucose levels was different, with maximal levels of 3.49+/-0.24 mmol/l reached 40 min after pilocarpine injection and a subsequent decrease to 1.25+/-0.40 mmol/l observed 200 min later. Pathologically increased neuronal activity induced by pilocarpine causes cell swelling followed by a reduction in the ECS volume fraction, which can contribute to the accumulation of toxic metabolites and lead to the start of epileptic discharges.
在氨基甲酸乙酯麻醉的大鼠中，使用四甲基铵选择性微电极的实时离子电渗疗法和扩散加权磁共振成像来测量毛果芸香碱给药240分钟后细胞外间隙体积分数α、曲折度λ和水的表观扩散系数（ADC(W)）。将获得的数据与通过脑内微透析测定的细胞外乳酸、葡萄糖和谷氨酸浓度以及乳酸/丙酮酸比值相关联。α和λ的对照值分别为0.19±0.004和1.58±0.01。应用毛果芸香碱后，100分钟后α降至0.134±0.012。此后α升高，140分钟后达到0.176±0.009。在整个实验过程中未观察到λ有显著变化。与对照值（603±11μm² s⁻¹）相比，应用毛果芸香碱100分钟后ADC(W)显著降低（549±8μm² s⁻¹）；到实验结束时，ADC(W)已恢复到对照值。乳酸、乳酸/丙酮酸比值、葡萄糖和谷氨酸的基础皮质水平分别为0.61±0.05 mmol/L、33.16±4.26、2.42±0.13 mmol/L和6.55±1.31μmol/L。应用毛果芸香碱导致乳酸、乳酸/丙酮酸比值和谷氨酸水平升高，在约100分钟内达到2.92±0.60 mmol/L、84.80±11.72和22.39±5.85μmol/L，随后在140分钟后降至对照值。葡萄糖水平的变化时间进程不同，毛果芸香碱注射后40分钟达到最高水平3.49±0.24 mmol/L，200分钟后观察到随后降至1.25±0.40 mmol/L。毛果芸香碱诱导的病理性神经元活动增加导致细胞肿胀，随后细胞外间隙体积分数降低，这可能导致有毒代谢物的积累并引发癫痫放电。
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