Literature DB >> 29620688

Effects of Branched-Chain Amino Acid Supplementation on Spontaneous Seizures and Neuronal Viability in a Model of Mesial Temporal Lobe Epilepsy.

Shaun E Gruenbaum1, Roni Dhaher2, Amedeo Rapuano3, Hitten P Zaveri4, Amber Tang2, Nihal de Lanerolle3, Tore Eid2,3.   

Abstract

BACKGROUND: The essential branched-chain amino acids (BCAAs) leucine, isoleucine, and valine have recently emerged as a potential novel treatment for medically refractory epilepsy. Blood-derived BCAAs can readily enter the brain, where they contribute to glutamate biosynthesis and may either suppress or trigger acute seizures. However, the effects of BCAAs on chronic (ie, spontaneous recurrent) seizures and epilepsy-associated neuron loss are incompletely understood.
MATERIALS AND METHODS: Sixteen rats with mesial temporal lobe epilepsy were randomized into 2 groups that could drink, ad libitum, either a 4% solution of BCAAs in water (n=8) or pure water (n=8). The frequency and relative percent of convulsive and nonconvulsive spontaneous seizures were monitored for a period of 21 days, and the brains were then harvested for immunohistochemical analysis.
RESULTS: Although the frequency of convulsive and nonconvulsive spontaneous recurrent seizures over a 3-week drinking/monitoring period were not different between the groups, there were differences in the relative percent of convulsive seizures in the first and third week of treatment. Moreover, the BCAA-treated rats had over 25% fewer neurons in the dentate hilus of the hippocampus compared with water-treated controls.
CONCLUSIONS: Acute BCAA supplementation reduces seizure propagation, whereas chronic oral supplementation with BCAAs worsens seizure propagation and causes neuron loss in rodents with mesial temporal lobe epilepsy. These findings raise the question of whether such supplementation has a similar effect in humans.

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Year:  2019        PMID: 29620688      PMCID: PMC6170745          DOI: 10.1097/ANA.0000000000000499

Source DB:  PubMed          Journal:  J Neurosurg Anesthesiol        ISSN: 0898-4921            Impact factor:   3.956


  71 in total

1.  Expression of a system L neutral amino acid transporter at the blood-brain barrier.

Authors:  H Matsuo; S Tsukada; T Nakata; A Chairoungdua; D K Kim; S H Cha; J Inatomi; H Yorifuji; J Fukuda; H Endou; Y Kanai
Journal:  Neuroreport       Date:  2000-11-09       Impact factor: 1.837

Review 2.  Transfer of glutamine between astrocytes and neurons.

Authors:  S Bröer; N Brookes
Journal:  J Neurochem       Date:  2001-05       Impact factor: 5.372

3.  Modulation of absence seizures by branched-chain amino acids: correlation with brain amino acid concentrations.

Authors:  F Dufour; K A Nalecz; M J Nalecz; A Nehlig
Journal:  Neurosci Res       Date:  2001-07       Impact factor: 3.304

4.  Function of leucine in excitatory neurotransmitter metabolism in the central nervous system.

Authors:  S M Hutson; E Lieth; K F LaNoue
Journal:  J Nutr       Date:  2001-03       Impact factor: 4.798

5.  Recurrent seizures and hippocampal sclerosis following intrahippocampal kainate injection in adult mice: electroencephalography, histopathology and synaptic reorganization similar to mesial temporal lobe epilepsy.

Authors:  V Bouilleret; V Ridoux; A Depaulis; C Marescaux; A Nehlig; G Le Gal La Salle
Journal:  Neuroscience       Date:  1999-03       Impact factor: 3.590

Review 6.  Glutamate uptake.

Authors:  N C Danbolt
Journal:  Prog Neurobiol       Date:  2001-09       Impact factor: 11.685

Review 7.  Mesial temporal lobe epilepsy: what have we learned?

Authors:  J Engel
Journal:  Neuroscientist       Date:  2001-08       Impact factor: 7.519

8.  Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathway.

Authors:  J C Anthony; F Yoshizawa; T G Anthony; T C Vary; L S Jefferson; S R Kimball
Journal:  J Nutr       Date:  2000-10       Impact factor: 4.798

Review 9.  Pathophysiology of hepatic encephalopathy: a new look at ammonia.

Authors:  Roger F Butterworth
Journal:  Metab Brain Dis       Date:  2002-12       Impact factor: 3.584

10.  Reduced inhibition of dentate granule cells in a model of temporal lobe epilepsy.

Authors:  Masayuki Kobayashi; Paul S Buckmaster
Journal:  J Neurosci       Date:  2003-03-15       Impact factor: 6.167

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  2 in total

Review 1.  Branched-Chain Amino Acids and Seizures: A Systematic Review of the Literature.

Authors:  Shaun E Gruenbaum; Eric C Chen; Mani Ratnesh Singh Sandhu; Ketaki Deshpande; Roni Dhaher; Denise Hersey; Tore Eid
Journal:  CNS Drugs       Date:  2019-08       Impact factor: 5.749

2.  Circulating Metabolites as Biomarkers of Disease in Patients with Mesial Temporal Lobe Epilepsy.

Authors:  Alexandre B Godoi; Amanda M do Canto; Amanda Donatti; Douglas C Rosa; Danielle C F Bruno; Marina K Alvim; Clarissa L Yasuda; Lucas G Martins; Melissa Quintero; Ljubica Tasic; Fernando Cendes; Iscia Lopes-Cendes
Journal:  Metabolites       Date:  2022-05-17
  2 in total

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