CSF GABA Levels Research Articles

JM-20 Treatment After MCAO Reduced Astrocyte Reactivity and Neuronal Death on Peri-infarct Regions of the Rat Brain.

Stroke is frequently associated with severe neurological decline and mortality, and its incidence is expected to increase due to aging population. The only available pharmacological treatment for cerebral ischemia is thrombolysis, with narrow therapeutic windows. Efforts aimed to identify new therapeutics are crucial. In this study, we look into plausible molecular and cellular targets for JM-20, a new hybrid molecule, against ischemic stroke in vivo. Male Wistar rats were subjected to 90min middle cerebral artery occlusion (MCAO) following 23h of reperfusion. Animals treated with 8mg/kg JM-20 (p.o., 1h after reperfusion) showed minimal neurological impairment and lower GABA and IL-1β levels in CSF when compared to damaged rats that received vehicle. Immunocontent of pro-survival, phosphorylated Akt protein decreased in the cortex after 24h as result of the ischemic insult, accompanied by decreased number of NeuN+ cells in the peri-infarct cortex, cornu ammonis 1 (CA1) and dentate gyrus (DG) areas. Widespread reactive astrogliosis in both cortex and hippocampus (CA1, CA3, and DG areas) was observed 24h post-ischemia. JM-20 prevented the activated Akt reduction, neuronal death, and astrocytes reactivity throughout the brain. Overall, the results reinforce the pharmacological potential of JM-20 as neuroprotective agent and provide important evidences about its molecular and cellular targets in this model of cerebral ischemia.

Effects of prenatal exposure to different colors on offsprings mood.

There is much evidence indicating that depression is influenced by the levels of neurotransmitters such as dopamine, GABA and adrenaline. The current study we designed to investigate the effect of exposure of pregnant rats to different colors on neurotransmitters level, as indicators of mood disorders in off springs. Five groups of pregnant female Wistar rats (eight rats in each group) were enrolled in this study. Dopamine, adrenaline and GABA concentration in sera of rats were measured using ELISA. The colors black and red elevated the GABA levels in serum and CSF while the colors green and blue decreased the GABA levels. The colors black and red also decreased the sera and CSF levels of dopamine compared to the control group. The concentration of adrenaline was increased following exposure to the colors black, red and blue but decreased only following color green exposure. These results showed serious changes in neurotransmitter levels due to exposure to different colors which can be translated as mood and behavior changes. It can be concluded that exposure during pregnancy can lead to postpartum behavioral changes even at adulthood and such changes can be made by colors.

KCNQ2 mutations: genotype-phenotype association beyond epilepsy

Background: KCNQ2 abnormalities were described in infants with benign familial neonatal seizures (BFNS) and epileptic encephalopathy (EE). Associated features possibly include abnormal neuroimaging findings such as hypomyelination and/or T2 high signal of basal ganglia. Methods: This report describes 4 infants carrying different heterozygous KCNQ2 variants and 2 infants with 20q13.33 deletions encompassing KCNQ2 gene. Results: The different KCNQ2 mutations led to EE in 3 patients and included a novel de novo missense variant, p.Arg201Cys/c.601C>T, in an infant with severe EE and global developmental delay, hyperkinetic movement disorder, autonomic dysfunction with chronic hypoventilation, apnea, low GABA levels in CSF, and hypomyelination. She died at age 3 years of respiratory failure. One patient with BFNS and normal MRI has a previously reported c.508delG frame shift mutation in KCNQ2. Of the two de novo 22q13.33 deletions (1.2Mb versus 254.1 Kb) the larger caused a more severe phenotype, including focal epilepsy from infancy until 4 years, moderate developmental delay and diffuse brain volume loss. Conclusions: Along with varied epilepsy phenotypes and neuroimaging findings KCNQ abnormalities were associated with severe autonomic dysfunction and reduced CSF GABA levels. This might have further treatment implications, besides that the altered potassium channel function itself presents a therapeutic target.

Manifestations respiratoires au cours du syndrome ‘DRESS’ : cohorte rétrospective et revue de la littérature

Recently we have developed a simple and sensitive assay for the measurement of GABA in fluids and tissues by high performance liquid chromatography [16]. The only sample preparation required is deproteinization and usually 100 μl of CSF is all that is required for a reliable determination of OABA. We have measured GABA CSF levels in patients with various neurological disorders as well as in a few control specimens. The control values, around 300 nM, agree with published results. Patients with Parkinson's disease or Huntington's chorea had CSF GABA levels ranging from 26–150 nM with occasional high values and are in general agreement with those reported by Enna et al. [7]. Cerebrospinal fluid GABA levels in patients with myoclonus, stroke, dystonia and other miscellaneous neurological disorders ranged from 50–600 nM, without any recognizable pattern. From the results obtained thus far, low levels of CSF GABA are not necessarily limited to patients with Huntington's chorea or Parkinson's disease.

Glutamate and GABA levels in CSF from patients affected by dementia and olivo-ponto-cerebellar atrophy.

The modifications in the CSF content of glutamate and GABA in patients afflicted with primary degenerative dementia (PDD) and olivo-ponto-cerebellar atrophy (OPCA) have been evaluated. Control subjects (with disk herniation) were also included in the study. The amino-acids assays were carried out utilizing enzymatic-bioluminescence technique. GABA levels in controls were 803 +/- 98 (n = 7) and in demented patients 702 +/- 98 (n = 7) pmol/ml. Glutamate levels were 2067 +/- 244 (n = 10) in controls, 1190 +/- 81 (n = 16) pmol/ml (vs controls p less than 0.01) in demented patients, and 1116 +/- 146 (vs controls p less than 0.01) in OPCA patients. These results suggest that CSF glutamate levels in severely demented patients might be a result of generalized neuronal loss in the brain with a reactive gliosis.

Fluoxetine Partly Exerts its Actions Through GABA: A Neurochemical Evidence

Fluoxetine, as a serotonin re-uptake inhibitor augments serotonin concentration within the synapse by inhibiting the serotonin transporter. The contribution of amino acids has also been shown in depression. We hypothesized that fluoxetine exerts its actions at least in part by intervening brain signaling operated by amino acid transmitters. Therefore the aim of this study is to supply neurochemical evidence that fluoxetine produces changes in amino acids in cerebrospinal fluid of rats. Sprague-Dawley rats were anesthetized and concentric microdialysis probes were implanted stereotaxically into the right lateral ventricle. Intraperitoneal fluoxetine (2.5 or 5 mg/kg) or physiological saline was administered and the probes were perfused with artificial cerebrospinal fluid at a rate of 1 mul/min. In the chronic fluoxetine group, the rats were treated daily with oral fluoxetine solution or inert syrup for 3 weeks. The microdialysis probes were placed on the 21st day and perfused the next day. Fluoxetine was ineffective in changing the cerebrospinal fluid GABA levels at the dose of 2.5 mg/kg but produced a significant increase in the perfusates following injection of 5 mg/kg of fluoxetine (P < 0.05). Oral fluoxetine administration (5 mg/kg) for 21 days also elevated the CSF GABA levels by approximately 2-fold (P < 0.05). L: -glutamic acid levels were not affected in all groups. These neurochemical findings show that fluoxetine, a selective serotonin re-uptake inhibitor affects brain GABA levels indirectly, and our results suggest that acute or chronic effects may be involved in beneficial and/or adverse effects of the drug.

P.1.g.001 Increased CSF cholecystokinin, NPY and GABA levels in pathological gambling

P.1.g.001 Increased CSF cholecystokinin, NPY and GABA levels in pathological gambling

303. Measurement of human cortical GABA synthesis in vivo

Studies of GABA receptors and CSF GABA levels have implicated the GABAergic system in mood disorders. Recently H magnetic resonance spectroscopy (MRS) has shown that cortical GABA is changed in unipolar depression. The mechanism of the changes is unknown and may hold clues for clinical effects and treatments. GABA synthesis may be reduced, or GABA turnover may be elevated by GABAergic overstimulation, reaching new, lower steady-state levels. Key to evaluating these possibilities is the ability to measure the synthesis of cortical GABA in humans in vivo. C MRS was used to detect the incorporation of the non-radioactive isotope C in GABA, glutamate, and glutamate during a 90-minute infusion of [1-C]glucose in three healthy volunteers. The GABA C2 time course was fitted with a single exponential function after removing the contribution from natural abundance labeling of the co-resonant N-acetylaspartate C3, showing that 2.4 6 2.1% (mean 6 s.d.) of the GABA pool is degraded and replaced per minute. Given a GABA concentration of 1.48 mmol g in healthy controls obtained from previous H MRS studies (Sanacora et al., Arch Psych 56:1043), the rate of synthesis of GABA was estimated to be 0.035 mmol min g, which is ;4% of the rate of the cortical tricarboxylic acid cycle. While more studies will more precisely define the rate, the results demonstrate the possibility of direct measurements of GABA synthesis in mood disorders.

GABA and brain abnormalities in schizophrenia

Some recent autopsy studies indicate that γ-aminobutyric acid (GABA) function is decreased in brain areas that involve some of the well-described structural changes observed in schizophrenia. The current study examined the relationship between CSF and plasma GABA levels and brain structural measures in schizophrenia. Sixty-two drug-free, physically healthy male patients with schizophrenia (DSM-IIIR) were evaluated for plasma and CSF GABA, as well as brain structural measures on CT scans. Plasma levels of GABA were associated with prefrontal sulcal widening and VBRs, but not global sulcal widening in the schizophrenic patients. CSF GABA measures were not associated with brain structural measures, but were associated with age and age of onset. The significant relationship between plasma GABA, but not CSF GABA, and specific brain morphology measures in schizophrenic patients suggests that if GABA transmission is impaired in schizophrenia, it is a local, but not global, phenomenon.

Neurotransmitter amino acids in cerebrospinal fluid of patients with Parkinson's disease

We measured the CSF and plasma levels of glutamate, glutamine, aspartate (only in plasma), asparagine, glutamine, glycine and GABA in 31 patients with Parkinson's disease and in 45 matched controls. We used an ion-exchange chromatography method. When compared to controls, PD patients had similar CSF levels of glutamate, glutamine, asparagine, and glycine higher CSF GABA levels higher plasma levels of glutamine, asparagine, and glycine, and lower plasma levels of aspartate. The CSF levels of the amino acids measured were not correlated with the clinical features of PD. Our results that CSF GABA levels are not decreased in PD as previously suggested.

Schizotypal features in relatives of schizophrenic patients with and without a family history of schizophrenia

Some recent autopsy studies indicate that γ-aminobutyric acid (GABA) function is decreased in brain areas that involve some of the well-described structural changes observed in schizophrenia. The current study examined the relationship between CSF and plasma GABA levels and brain structural measures in schizophrenia. Sixty-two drug-free, physically healthy male patients with schizophrenia (DSM-IIIR) were evaluated for plasma and CSF GABA, as well as brain structural measures on CT scans. Plasma levels of GABA were associated with prefrontal sulcal widening and VBRs, but not global sulcal widening in the schizophrenic patients. CSF GABA measures were not associated with brain structural measures, but were associated with age and age of onset. The significant relationship between plasma GABA, but not CSF GABA, and specific brain morphology measures in schizophrenic patients suggests that if GABA transmission is impaired in schizophrenia, it is a local, but not global, phenomenon.

Somatostatin, β-endorphin, and prolactin levels in human cerebrospinal fluid during the γ-vinyl-GABA treatment of patients with complex partial epilepsy

The anticonvulsant action of the new anticonvulsant drug γ-vinyl-GABA (GVG) is obviously mediated by elevation of the concentration of GABA in the brain. The effect of GVG administration on other transmitter systems is not fully known in humans. We studied the possible interactions of GVG administration with peptidergic systems. Included in this study were 67 patients with complex partial epilepsy (CPS). The first CSF sample was taken before GVG administration. The second CSF sample was taken after 3 months of GVG treatment (3 g/day). Thereafter half of the responders (50% decrease in seizure frequency or clear improvement in global performance) received 3 g/day and the other half received 1.5 g/day for the next three months, after which the third CSF sample was taken. Somatostatin 9SLI), β-endorphin (β-EP), and prolactin (PROL) levels in CSF were measured by radioimmunoassay. Total GABA (tGABA) and GVG levels in CSF were measured by high performance liquid chromatography. After 3 months of GVG treatment there was a slight increase in the β-EP (p=0.027, Student's paired t-test), which was not found after 6 months of GVG administration. Both SLI and PROL were stable during the study. Peptide levels were not connected to the clinical response to GVG, GVG dosage, or to tGABA levels in the CSF. In conclusion, the elevation of GABA levels in the brain during GVG treatment apparently does not induce long-term interactions with the peptidergic systems studied.

Disappearance of neonatal seizures and low CSF GABA levels after treatment with vitamin B 6

In an infant with neonatal seizures, CSF GABA levels were determined before and after treatment with vitamin B 6. Before onset of treatment, the level of GABA in CSF was very low (13 pmol/ml). Injection of vitamin B 6 blocked the seizures immediately. When GABA level in CSF was again analysed after continued treatment with vitamin B 6, a value of 127 pmol/ml was determined, which is within the normal concentration range in children. The data substantiate previous findings in brain tissue from a patient with vitamin B 6-dependent seizures, and strongly indicate that impairment of central GAB Aergic activity was the cause of the seizures.

Free and conjugated GABA in human cerebrospinal fluid: Effect of degenerative neurologic diseases and isoniazid

γ-Aminobutyric acid (GABA) was measured in CSF as such and following acid hydrolysis by the ion-exchange/fluorometric method. The conjugated GABA level was obtained by subtracting the free GABA level from the total GABA level. Results showed that at room temperature, while the free GABA level increased, the level of conjugated GABA decreased in a linear fashion during the first 24 h ( r = −0.974; P < 0.001). Aging and CSF conjugated GABA levels were inversely correlated ( r = −0.613; P < 0.05). Unlike free GABA levels, the levels of conjugated GABA were not altered in Huntington's disease, Parkinson's disease, cerebellar ataxias, dementias, epilepsy and multiple sclerosis compared to controls. In patients with Huntington's disease, on administration of isoniazid at 900 mg/day, along with pyridoxine at 100 mg/day, a 4-fold increase of both free ( P < 0.005) and conjugated GABA ( P < 0.0025) was seen. The results indicate that while total GABAergic peptides are not altered in several of the neurologic disease studied, drugs such as isoniazid and/or pyridoxine can significantly elevate both free and conjugated GABA levels in human CSF.

Cerebrospinal fluid GABA levels in children with infantile spasms.

The mean CSF GABA level in 22 children with infantile spasms was significantly lower than in 35 controls. There was no significant difference between the CSF GABA levels in untreated children and those treated with anticonvulsants, or between uncontrolled and temporarily controlled patients. After treatment with ACTH, CSF GABA levels were lower than before treatment, and seizures disappeared. Brain GABAergic neuronal function may be disturbed in children with infantile spasms, but the decreased CSF GABA level does not directly correlate with the seizures of infantile spasms.

Gamma-aminobutyric acid (GABA) in cerebrospinal fluid.

Levels of gamma-aminobutyric acid (GABA) in cerebrospinal fluid (CSF) were measured by radioreceptor assay (RRA) in 25 normal controls and in 121 patients with various central nervous system disorders. CSF-GABA levels could be measured down to 5 pmoles/ml reliably by this assay. In normal controls, the mean (+/- SEM) GABA level in CSF was 127 +/- 5.2 pmoles/ml. There was no correlation between age, sex and the CSF-GABA level in normal controls. The lowest CSF-GABA level, which was 60 +/- 6.0 pmoles/ml, was observed in alcoholic patients suffering from cerebellar ataxia. The CSF-GABA levels were quite low in patients with Alzheimer's disease, late cortical cerebellar atrophy, neuro-Behçet's syndrome, olivopontocerebellar atrophy, Huntington's chorea, Parkinson's disease and cerebral hemorrhage. On the other hand, the CSF-GABA levels of meningitis patients were significantly increased. These findings suggest that measuring the CSF-GABA level is quite beneficial in the diagnosis and pathophysiological determinations of some diseases.

Relationship between GABA concentrations in cerebrospinal fluid and seizure excitability.

Various studies suggest that alterations in GABAergic function may be connected to epileptic seizures. Low CSF GABA levels have been reported in epilepsy and also febrile convulsions of children. In this study the pentetrazole seizure threshold of dogs was compared with the concentration of GABA in the CSF and blood plasma. A highly significant positive correlation was found between seizure excitability and CSF GABA level, but not between CSF and plasma GABA concentrations.

CSF GABA in normal subjects and patients with depression, schizophrenia, mania, and anorexia nervosa.

The authors examined the CSF GABA of 87 subjects: 29 normal control subjects, 11 patients with schizophrenia, 26 with depression, 6 with mania, and 15 with anorexia nervosa. Depressed patients had significantly lower CSF GABA levels than did normal subjects. This finding suggests that GABA may have a direct or indirect association with depressive affective disorders.

Preliminary studies on CSF gamma-aminobutyric acid levels in psychiatric patients before and during treatment with different psychotropic drugs

1. 1. Measurements of CSF GABA levels were performed on different groups of psychiatric patients. 2. 2. Two different methods were used for determination of CSF GABA concentration: a) gaschromatography/ mass spectrometry and b) amino acid analysis with fluorescence detection. 3. 3. No difference in CSF GABA levels between control patients and untreated schizophrenic patients was seen. 4. 4. An increase of CSF GABA levels was found after 30 days of treatment with sulpiride and during chronic treatment with different neuroleptics for many years in long-stay hospitalized schizophrenic patients. 5. 5. In short-stay hospitalized schizophrenic patients after a period of about 6 weeks of treatment with different neuroleptics in combination with benzodiazepines and antiparkinsonian drugs a decrease of CSF GABA levels compared with control patients was observed. 6. 6. It is assumed that the increase of GABA in CSF could be indicative for a neuroleptic drug. The simultaneous administration of benzodiazepines and antiparkinsonian drugs might be responsible for the decrease in CSF GABA levels.

CSF GABA in psychotic disorders.

CSF GABA levels were not significantly different in a group of drug-free psychotic patients compared to a group of psychotic patients at two points during haloperidol treatment or a neurological comparison group. In the untreated group, CSF GABA was significantly negatively correlated with clinical ratings of anxiety and agitation. Early in haloperidol treatment CSF GABA was significantly positively correlated with CSF HVA.