Brain metabolism and diffusion in the rat cerebral cortex during pilocarpine-induced status epilepticus

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• 作者：Karel Slais ; Ivan Vorisek ; Norbert Zoremba ; Ales Homola ; Lesia Dmytrenko ; Eva Sykova
• 关键词：Diffusion ; ADC_W ; Microdialysis ; Pilocarpine ; Epilepsy ; Glucose ; Glutamate ; Pyruvate ; Lactate ; Potassium
• 刊名：Experimental Neurology
• 出版年：2008
• 出版时间：January 2008
• 年：2008
• 卷：209
• 期：1
• 页码：145-154
• 全文大小：1033 K

文摘

The real-time iontophoretic method using tetramethylammonium-selective microelectrodes and diffusion-weighted magnetic resonance imaging were used to measure the extracellular space volume fraction α, tortuosity λ 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 α and λ were 0.19 ± 0.004 and 1.58 ± 0.01, respectively. Following pilocarpine application, α decreased to 0.134 ± 0.012 100 min later. Thereafter α increased, reaching 0.176 ± 0.009 140 min later. No significant changes in λ were observed during the entire time course of the experiment. ADC_W was significantly decreased 100 min after pilocarpine application (549 ± 8 μm² s^{− 1}) compared to controls (603 ± 11 μm² 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 μmol/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 μmol/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.