Analysis of cerebrospinal fluid γ‐aminobutyric acid by capillary electrophoresis with laser‐induced fluorescence detection

Casado, Mercedes; Molero, Marta; Sierra, Cristina; García‐Cazorla, Àngels; Ormazábal, Aída; Artuch, Rafael

doi:10.1002/elps.201300261

Cited by 12 publications

(13 citation statements)

References 39 publications

(77 reference statements)

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“…A key finding of the present study was that neonates displayed significantly lower in vivo brain GABA+ levels than children in both the BG and cerebellum. Previous ex vivo studies of postmortem brains and cerebrospinal fluid also reported significant increases in GABA concentrations with age . Therefore, it is likely that in vivo GABA concentrations in the BG and cerebellum are lower in neonates compared with children, and that they increase with development.…”

Section: Resultsmentioning

confidence: 95%

In vivo estimation of gamma‐aminobutyric acid levels in the neonatal brain

et al. 2016

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Gamma‐aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain, and plays a key role in brain development. However, the in vivo levels of brain GABA in early life are unknown. Using edited MRS, in vivo GABA can be detected as GABA+ signal with contamination of macromolecule signals. GABA+ is evaluated as the peak ratio of GABA+/reference compound, for which creatine (Cr) or water is typically used. However, the concentrations and T 1 and T 2 relaxation times of these references change during development. Thus, the peak ratio comparison between neonates and children may be inaccurate. The aim of this study was to measure in vivo neonatal brain GABA+ levels, and to investigate the dependency of GABA levels on brain region and age. The basal ganglia and cerebellum of 38 neonates and 12 children were measured using GABA‐edited MRS. Two different approaches were used to obtain GABA+ levels: (i) multiplying the GABA/water ratio by the water concentration; and (ii) multiplying the GABA+/Cr by the Cr concentration. Neonates exhibited significantly lower GABA+ levels compared with children in both regions, regardless of the approach employed, consistent with previous ex vivo data. A similar finding of lower GABA+/water and GABA+/Cr in neonates compared with children was observed, except for GABA+/Cr in the cerebellum. This contrasting finding resulted from significantly lower Cr concentrations in the neonate cerebellum, which were approximately 52% of those of children. In conclusion, care should be taken to consider Cr concentrations when comparing GABA+/Cr levels between different‐aged subjects.

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Section: Resultsmentioning

confidence: 95%

In vivo estimation of gamma‐aminobutyric acid levels in the neonatal brain

et al. 2016

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“…Moreover, we know that a subset of patients with SSADHD has a more severe phenotype, featuring adult-onset epilepsy (Parviz et al 2014), and there have been instances of SUDEP (sudden unexplained death in epilepsy) in adulthood (Lapalme-Remis et al 2015; Knerr et al 2010; Gibson and Pearl, unpublished observation). Previously, Casado and coworkers (2014) documented that GABA levels in cerebrospinal fluid from 55 pediatric controls showed a progressive increase with age. Unfortunately, we could not assess this age-related parameter in our control cohort since information on age characteristics was limited.…”

Section: Discussionmentioning

confidence: 97%

“…Patient age range was 5–41 years (median, 8 years), and ages were available for all. Clinical details were not available on patients at the time of sample shipment, and to our knowledge none of the patients was concurrently receiving vigabatrin or other antiepileptic which may have artefactually elevated plasma total GABA, as is the case for GABA in cerebrospinal fluid for patients receiving vigabatrin (Gibson et al 1995; Casado et al 2014). …”

Section: Methodsmentioning

confidence: 99%

Correlation of blood biomarkers with age informs pathomechanisms in succinic semialdehyde dehydrogenase deficiency (SSADHD), a disorder of GABA metabolism

Jansen

Vogel

Salomons

et al. 2016

J of Inher Metab Disea

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We hypothesized that blood levels of GABA and γ-hydroxybutyric acid (GHB), biomarkers of succinic semialdehyde dehydrogenase deficiency (SSADHD), would correlate with age. GABA and GHB were quantified in plasma and red blood cells (RBCs) from eighteen patients (age range 5–41 years; median 8). Both metabolites negatively correlated with age (P<0.05). Plasma and RBC GHB declined with age, reaching a nadir and approximate steady-state by 10 years. Declining plasma GABA achieved this approximate steady state at 30–40 years of age. These biomarker relationships may reflect further GABA- and GHB-ergic neurotransmission imbalances that correlate with the onset of adolescent/adulthood neuropsychiatric morbidity and epilepsy in SSADHD.

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“…7,8 Our aim was to analyse the CSF free-GABA values in a large cohort of patients with different neuropaediatric disorders, by assessing clinical, biochemical, and molecular data. Although there are a few reports on small groups of patients, they emphasize only the influence of antiepileptic drugs (AEDs) and mainly focus on patients with epilepsy.…”

Section: Aedmentioning

confidence: 99%

“…7,8 Our aim was to analyse the CSF free-GABA values in a large cohort of patients with different neuropaediatric disorders, by assessing clinical, biochemical, and molecular data. …”

mentioning

confidence: 99%