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Increased branched‐chain amino acids at baseline and hours before a spontaneous seizure in the human epileptic brain
Author(s) -
Ong Caroline,
Damisah Eyiyemisi C.,
Gruenbaum Shaun E.,
Dhaher Roni,
Deng Yanhong,
Sandhu Mani Ratnesh S.,
Zaveri Hitten P.,
Spencer Dennis D.,
Eid Tore
Publication year - 2021
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.16920
Subject(s) - epilepsy , microdialysis , glutamine , extracellular , glutamate receptor , medicine , extracellular fluid , chemistry , amino acid , neuroscience , biology , biochemistry , receptor
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.