Measuring human brain GABA in vivo
ABSTRACT Gamma-aminobutyric acid (GABA) plays a pivotal role in suppressing the origin and spread of seizure activity. Low occipital
lobe GABA was associated with poor seizure control in patients with complex partial seizures. Vigabatrin irreversibly inhibits
GABA-transaminase, raising brain and cerebrospinal fluid (CSF) GABA concentrations. The effect of vigabatrin on occipital
lobe GABA concentrations was measured by in vivo nuclear magnetic-resonance spectroscopy. Using a single oral dose of vigabatrin,
the rate of GABA synthesis in human brain was estimated at 17% of the Krebs cycle rate. As the daily dose of vigabatrin was
increased to up to 3 g, the fractional elevation of brain GABA was similar to CSF increase. Doubling the daily dose from 3
to 6g failed to increase brain GABA further. Increased GABA concentrations appear to reduce GABA synthesis in humans as it
does in animals. With traditional antiepileptic drugs, remission of the seizure disorder was associated with normal GABA levels.
With vigabatrin, elevated CSF and brain GABA was associated with improved seizure control. Vigabatrin enhances the vesicular
and nonvesicular release of GABA. The release of GABA during seizures may be mediated in part by transporter reversal that
may serve as an important protective mechanism. During a seizure, this mechanism may be critical in stopping the seizure or
preventing its spread.
Article: Evaluation of GABA system and cell damage in parahippocampus of patients with temporal lobe epilepsy showing antiepileptic effects after subacute electrical stimulation.[show abstract] [hide abstract]
ABSTRACT: The gamma-aminobutyric acid (GABA) system and neuronal loss were evaluated in the parahippocampal cortex (PHC) of patients with intractable mesial temporal lobe epilepsy (MTLE) who received subacute electrical stimulation and showed antiepileptic effects. GABA tissue content, GABA(A) and benzodiazepine (BZD) receptor levels, as well as neuronal density were determined in PHC of five patients (ESAE group) with an MTLE history of 14.8 +/- 2.5 years and seizure frequency of 11 +/- 2.9 per month, two (40%) of them with mesial sclerosis. This group demonstrated antiepileptic effects after subacute electrical stimulation (130 Hz, 450 micros, 200-400 microA), applied continuously during 16 to 20 days in PHC. Values were compared with those obtained from patients with severe MTLE (history of 21.7 +/- 2.8 years and seizure frequency of 28.2 +/- 14 per month) in whom electrical stimulation did not induce antiepileptic effects (ESWAE group, n = 4), patients with MTLE in whom no electrical stimulation was applied (MTLE group, n = 4), and autopsy material acquired from subjects without epilepsy (n = 4 obtained from three subjects). The ESAE group demonstrated high GABA tissue levels (219%), as well as a significantly higher cell count (58.5%) when compared with the MTLE group. The ESWAE group showed enhanced BZD-receptor levels (38%), whereas their values for GABA tissue levels and GABA(A) receptor were similar to those obtained from the MTLE group. It is suggested that subacute electrical stimulation of PHC is more effective in patients with less severe epilepsy, an effect associated with a high GABA tissue content and a low rate of cell loss.Epilepsia 06/2004; 45(5):459-66. · 3.96 Impact Factor