Neurometabolic effects of ACTH on free amino compounds in opsoclonus-myoclonus syndrome.

To evaluate the possible role of central free amino compounds in pediatric opsoclonus-myoclonus syndrome (OMS), 21 cerebrospinal fluid (CSF) amino compounds were measured by an amino acid analyzer or mass spectroscopy in 74 anesthetized children, 54 with OMS and 20 age-matched neurological controls. In OMS, only phosphoethanolamine was increased compared to controls; OMS severity and duration had significant converse effects on alanine and phosphoethanolamine. In contrast, corticotropin (ACTH) treatment was associated with increased alanine and phenylalanine, and decreased taurine compared to controls and untreated OMS, and increased glutamine, lysine, ornithine, and tyrosine compared to untreated OMS. Other than low taurine, these effects were not found with corticosteroid treatment, and non-steroidogenic immunotherapy had no effect. The ACTH dose-association was most apparent for alanine and phosphoethanolamine, but lysine and ornithine were also higher in the high-dose ACTH group. There were no significant disease- or treatment-associated perturbations in GABA, glycine, or other amino acids. These data suggest a unique pattern of ACTH effects on non-neurotransmitter CSF amino compounds, for the most part not shared by steroids.

Cabergoline scavenges peroxynitrite enhanced by L-DOPA therapy in patients with Parkinson's disease.

Long-term or high-dose L-DOPA therapy in patients with Parkinson's disease (PD) may accelerate degeneration of dopaminergic neurons, possibly by increasing oxidative stress. To investigate the effects of cabergoline on peroxynitrite-mediated oxidative damage caused by L-DOPA, the concentration of 3-nitrotyrosine in cerebrospinal fluid (CSF) of 18 PD patients was compared with that in 20 normal controls. The concentration of 3-nitrotyrosine in patients following L-DOPA therapy was significantly higher than in untreated PD patients and controls. On the other hand, the concentration in PD patients after cabergoline therapy was significantly lower than in PD patients after L-DOPA therapy alone. These data suggest that cabergoline scavenges peroxynitrite induced by L-DOPA in patients with PD.

Detection of 28 neurotransmitters and related compounds in biological fluids by liquid chromatography/tandem mass spectrometry.

This work presents two liquid chromatography/tandem mass spectrometry (LC/MS/MS) acquisition modes: multiple reaction monitoring (MRM) and neutral loss scan (NL), for the analysis of 28 compounds in a mixture. This mixture includes 21 compounds related to the metabolism of three amino acids: tyrosine, tryptophan and glutamic acid, two pterins and five deuterated compounds used as internal standards. The identification of compounds is achieved using the retention times (RT) and the characteristic fragmentations of ionized compounds. The acquisition modes used for the detection of characteristic ions turned out to be complementary: the identification of expected compounds only is feasible by MRM while expected and unexpected compounds are detected by NL. In the first part of this work, the fragmentations characterizing each molecule of interest are described. These fragmentations are used in the second part for the detection by MRM and NL of selected compounds in mixture with and without biological fluids. Any preliminary extraction precedes the analysis of compounds in biological fluids.

An assessment of progression of brain edema with amino acid levels in cerebrospinal fluid and changes in electroencephalogram in an adult cat model of cold brain injury.

We investigated the relationship between the changes of the electroencephalogram (EEG) and concentration of amino acids (AAs) in cerebrospinal fluid (CSF) using a model of cold brain injury. A cold injury was made over the motor area of anesthetized adult cats (n = 45). The AAs in CSF from cisterna magna and in the blood were assayed by liquid chromatography. Frequency components and spike discharges/100 s in EEG were evaluated. Data were obtained before production of the lesion and every hour for 8 hours after the lesion was made. The AA-levels and EEG after the lesion was made were compared with those obtained in the controls and the sham operation group: S-group (n = 10) which were not significantly different. Glutamate and aspartate were not detected but methionine and serine were detected in the control CSF and S-group. These AAs increased during the first 4 hours (p < 0.05) and decreased thereafter. Significant increases in spike discharge and disappearance of fast wave (p < 0.02), and increase in AAs were concurrently detected. The AAs originated from necrosis in the lesion. During the next 4 hours, increase of phenylalanine, tyrosine, and valine continued (p < 0.05). Slow wave components (p < 0.02) and precursor AAs of neurotransmitters in CSF increased in association with expansion of edema fluid. In conclusion, our findings showed that changes in the concentration of AAs in CSF are useful indices of progression of edema associated with brain contusion.