Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Epilepsia. 2021 Jun;62(6):e88-e97. doi: 10.1111/epi.16920. Epub 2021 May 5.
The objective of this study was to monitor the extracellular brain chemistry dynamics at baseline and in relation to spontaneous seizures in human patients with refractory epilepsy. Thirty patients with drug-resistant focal epilepsy underwent intracranial electroencephalography and concurrent brain microdialysis for up to 8 continuous days. Extracellular brain glutamate, glutamine, and the branched-chain amino acids (BCAAs) valine, leucine, and isoleucine were quantified in the dialysis samples by liquid chromatography-tandem mass spectrometry. Extracellular BCAAs and glutamate were chronically elevated at baseline by approximately 1.5-3-fold in brain regions of seizure onset and propagation versus regions not involved by seizures. Moreover, isoleucine increased significantly above baseline as early as 3 h before a spontaneous seizure. BCAAs play important roles in glutamatergic neurotransmission, mitochondrial function, neurodegeneration, and mammalian target of rapamycin signaling. Because all of these processes have been implicated in epilepsy, the results suggest a novel role of BCAAs in the pathogenesis of spontaneous seizures.
本研究旨在监测难治性癫痫患者基线时及自发性癫痫发作时的细胞外脑化学动力学。30 例耐药性局灶性癫痫患者接受颅内脑电图和连续 8 天的脑微透析。通过液相色谱-串联质谱法对透析样本中的细胞外谷氨酸、谷氨酰胺和支链氨基酸（BCAA）缬氨酸、亮氨酸和异亮氨酸进行定量。与未受癫痫影响的区域相比，发作起始和传播区域的细胞外 BCAA 和谷氨酸在基线时慢性升高约 1.5-3 倍。此外，异亮氨酸早在自发性癫痫发作前 3 小时就明显高于基线。BCAA 在谷氨酸能神经传递、线粒体功能、神经退行性变和雷帕霉素靶蛋白信号传导中发挥重要作用。由于所有这些过程都与癫痫有关，因此研究结果表明 BCAA 在自发性癫痫发作发病机制中具有新的作用。
