Regionally infused lidocaine can dose-dependently protect the ischemic spinal cord in rabbits and may be associated with the EAA changes.

OBJECTIVE: In our previous study, we found that lidocaine, infused through the abdominal aorta, could protect the spinal cord against the ischemia-reperfusion (I/R) injury caused by aortic occlusion. However, whether lidocaine protective effects have dose-dependent properties and its underlying mechanisms still remain unclear. This study was designed to investigate whether regionally infused lidocaine could dose-dependently protect spinal cord against I/R injury in rabbits and its underlying mechanism. METHODS: 46 New Zealand white rabbits were randomized into six groups: Group NS (normal saline control); Group L10 (lidocaine 10 mg/kg); Group L20 (lidocaine 20 mg/kg); Group L40 (lidocaine 40 mg/kg); Group L80 (lidocaine 80 mg/kg) and Group Sham. In Group NS, Group L10, Group L20, Group L40 and Group L80, spinal cord ischemia was induced by infrarenal aortic occlusion for 30 min. The sham group did not receive spinal cord ischemia. During the occlusion, normal saline or lidocaine at different doses was infused continuously through a catheter into the clamped abdominal aorta respectively. Neurologic behavior functions were assessed according to the Tarlov scale system at the moments of 0, 6, 24 and 48 h after reperfusion. The neural injuries were evaluated by the histological examination and the count of normal α-motor neurons in the ventral horn. The levels of excitatory amino acids (EAAs) in the spinal cord, including glutamate (Glu) and aspartic acid (Asp), were analyzed by high performance liquid chromatography with fluorescence detection. RESULTS: The Tarlov scales in the Group L20 and the Group L40 were significantly higher than those in the Group NS at 24 and 48 h after reperfusion (P < 0.05). 12.5 % animals in Group L40 and 25 % animals in Group L20 were paraplegic versus 75 % animals in Group NS at 48 h after reperfusion (P < 0.05). The median of normal α-motor neurons in the L20, L40 and L80 groups was 7.5, 9 and 5 respectively which was significantly higher than in the NS group (count 0, P < 0.05). The levels of L-ASP and L-Glu remarkably decreased in the Group L10 and the Group L40 compared to Group NS (P < 0.05). CONCLUSIONS: These data revealed that regional administration of lidocaine through the abdominal aorta can provide dose-dependent protection on spinal cord I/R in rabbits. Inhibition of EAA release may be one of the underlying mechanisms.

Behavioural and molecular endophenotypes in psychotic disorders reveal heritable abnormalities in glutamatergic neurotransmission.

Psychotic disorders such as schizophrenia are biologically complex and carry huge population morbidity due to their prevalence, persistence and associated disability. Defined by features such as delusions and hallucinations, they involve cognitive dysfunction and neurotransmitter dysregulations that appear mostly to involve the dopaminergic and glutamatergic systems. A number of genetic and environmental factors are associated with these disorders but it has been difficult to identify the biological pathways underlying the principal symptoms. The endophenotype concept of stable, heritable traits that form a mechanistic link between genes and an overt expression of the disorder has potential to reduce the complexity of psychiatric phenotypes. In this study, we used a genetically sensitive design with individuals with a first episode of psychosis, their non-affected first-degree relatives and non-related healthy controls. Metabolomic analysis was combined with neurocognitive assessment to identify multilevel endophenotypic patterns: one concerned reaction times during the performance of cognitive and emotional tests that have previously been associated with the glutamate neurotransmission system, the other involved metabolites involved directly and indirectly in the co-activation of the N-methyl-D-aspartate receptor, a major receptor of the glutamate system. These cognitive and metabolic endophenotypes may comprise a single construct, such that genetically mediated dysfunction in the glutamate system may be responsible for delays in response to cognitive and emotional functions in psychotic disorders. This focus on glutamatergic neurotransmission should guide drug discovery and experimental medicine programmes in schizophrenia and related disorders.

Different serine and glycine metabolism in patients with schizophrenia receiving clozapine.

Dysfunction of the N-methyl-d-aspartate receptor, which is modulated by excitatory amino acids (EAA), is involved in the pathophysiology of schizophrenia. The effects of antipsychotics on EAA metabolism are uncertain. Positive clinical effects of treatment with antipsychotics were not always associated with changes in EAA serum levels in patients with schizophrenia in clinical trials. To examine EAA serum levels in relation to the intensity of psychotic symptoms and the type of medication received we compared these variables among patients with schizophrenia (n = 49) treated with first (FGA) or second (SGA) generation antipsychotics or clozapine. Glutamate, aspartate, glycine, total serine and d-serine serum levels were measured by High Performance Liquid Chromatography. The Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) were used to assess symptoms of schizophrenia. Lower average levels of glycine and total serine were found in the serum of patients receiving clozapine when compared to the groups of patients treated with FGA or SGA. There were no differences in serum glutamate, aspartate or d-serine levels or in the intensity of schizophrenic symptoms assessed by PANSS or SANS among the groups of patients treated with FGA or SGA or clozapine. Lower glycine and total serine serum levels could be caused by the particular characteristics of the population of patients receiving clozapine rather than as an effect of the clozapine. The results suggest selective deficiency of l-serine synthesis in the patients with resistance to non-clozapine treatment. It might be an unique biochemical and pathophysiological characteristic of the treatment-resistance in schizophrenia.

Predictive value of selected biochemical markers of brain damage for functional outcome in ischaemic stroke patients.

BACKGROUND AND PURPOSE: Previous studies suggested that biochemical markers of brain damage could act as prognostic factors in ischaemic stroke. The aim of the present study was to assess predictive value of the selected biomarkers S100B protein, neuron-specific enolase (NSE), C-reactive protein (CRP) and D-dimers, as well as GABA and excitatory amino-acids (EAA) measured in blood for 3-month functional outcome in ischaemic stroke patients. MATERIAL AND METHODS: We investigated 54 patients with ischaemic stroke (mean age: 73.3 +/-11.7). Serum concentrations of S100B, NSE, CRP, EAA and GABA, as well as plasma concentrations of D-dimers, were assessed in blood samples taken at admission and at 12, 24, and 72 hours after stroke onset. Functional status was measured with modified Rankin Scale (mRS) 3 months after stroke onset. RESULTS: Significant independent predictors of outcome in ischaemic stroke patients 3 months after stroke were: S100B level at 12 h (OR: 1.7; 95% CI: 0.5-7.0; p = 0.007), NSE at 12 h (OR: 2.4; 95% CI: 0.7-8.1; p = 0.037), 24 h (OR: 10.2; 95% CI: 2.4-43.2; p = 0.0007), and 72 h (OR: 10.2; 95% CI: 2.3-45.0; p = 0.0001), CRP at 72 h (OR: 8.3; 95% CI: 1.5-45.4; p = 0.009) and D-dimers at admission (OR: 4.8; 95% CI: 1.1-20.7; p = 0.02), 24 h (OR: 5.5; 95% CI: 1.4-20.9; p = 0.004), and 72 h after stroke onset (OR: 2.7; 95% CI: 0.6-11.8; p = 0.01). CONCLUSIONS: The results of the present study are consistent with previous evidence indicating that selected biomarkers could help in prediction of the outcome in ischaemic stroke early after symptoms onset.

[Curative effect and possible mechanisms of topiramate in treatment of Tourette syndrome in rats].

OBJECTIVE: The pathogenesis of Tourette syndrome (TS) is associated with the disorders of neurotransmitters, such as dopamine (DA) and excitatory amino acids (EAA). Antiepileptic drugs such as topiramate have shown some effects on TS, but the mechanism has not been clearly identified. The objective of the research was to evaluate the relationship between the pathogenesis of TS and abnormality of neurotransmitters by determining the levels of brain free DA and plasma EAA in iminodipropionitrile (IDPN) induced head twitch response (HTR) rats, and to investigate the effects of topiramate on HTR induced by IDPN. METHODS: Forty-eight Sprague-Dawley rats were randomly divided into six groups: blank control, TS model, and haloperidol-(0.5 mg/kg) and topiramate-treated (5, 10 and 20 mg/kg). HTR was induced by 7-day peritoneal injections of IDPN (150 mg/kg daily) and was used as TS model. Brain free DA levels and plasma levels of EAA were measured using ELISA and high performance liquid chromatography respectively 35 days after haloperidol or topiramate administration. RESULTS: Brain free DA levels were significantly lower and plasma EAA levels were significantly higher in the TS model group compared with those in the blank control group (P<0.05). Topiramate of 10 and 20 mg/kg significantly decreased the frequency of IDPN-induced HTR and significantly increased the level of brain free DA when compared with the TS model group (P<0.05). Topiramate of 20 mg/kg treatment as haloperidol treatment significantly decreased plasma EAA levels compared with the TS model group (P<0.05). CONCLUSIONS: The pathogenesis of TS is related to the super-sensitivity of DA receptor in the center nervous system and the over-effect of plasma EAA. Topiramate can reduce IDPN-induced HTR, probably through the inhibition of DA and DA-receptor combination in the brain and the secretion and release of plasma EEA.

Determination of excitatory amino acids in biological fluids by capillary electrophoresis with optical fiber light-emitting diode induced fluorescence detection.

The capillary electrophoresis (CE) system with optical fiber light-emitting diode (optical fiber LED) induced fluorescence detector was developed for the analysis of the excitatory amino acids (EAAs) tagged with naphthalene-2,3-dicarboxaldehyde (NDA). The separation of EAAs was carried out in an uncoated fused-silica capillary (50 cm x 75 microm i.d.) with a buffer of 10 mM borate at pH 9.3 and an applied voltage of 20 kV. High sensitivity was obtained by the use of optical fiber LED induced fluorescence detector with a violet LED as the excitation light source. The limits of detection (S/N = 3) for glutamic acid (Glu) and aspartic acid (Asp) were 2.1 x 10(-8) and 2.3 x 10(-8) M, respectively. The detection approach was successfully applied to the analysis of Glu and Asp in biological fluids including human serum, rabbit serum and human cerebrospinal fluid (CSF) with satisfactory results.

A facile and sensitive chemiluminescence detection of amino acids in biological samples after capillary electrophoretic separation.

It was found that native amino acids enhanced the chemiluminescence (CL) reaction between luminol and BrO(-) in an alkaline aqueous solution. This has led to the development of a facile and highly sensitive CL detection scheme for the determination of amino acids in biological samples after capillary electrophoretic (CE) separation. The CE-CL conditions were optimized. An electrophoretic buffer of 2.5 x 10(-2) M sodium borate (pH 9.4) containing 1 x 10(-4) M luminol was used. The oxidizer solution of 8 x 10(-4) M NaBrO in 0.1 M sodium carbonate buffer solution (pH 12.5) was introduced post-column. Under the optimal conditions, the detection limits were 1.0 x 10(-7) M for glutamic acid (Glu) and 1.3 x 10(-7) M (S/N = 3) for aspartic acid (Asp). The relative standard deviations (RSDs) of peak area and migration time were in the ranges of 3.8-4.3% and 1.4-1.6%, respectively. The present method was applied to the determination of excitatory amino acids (i.e., Asp and Glu) in rat brain tissue and monkey plasma. The levels of these major excitatory amino acids in monkey plasma were quantified for the first time and found to be 1.17 +/- 0.17 x 10(-5) M (mean +/- SD, n = 6) for Glu and 1.64 +/- 0.19 x 10(-6) M for Asp, which were comparable with the levels in human plasma.

Excitatory aminoacid neurotransmitters in schizophrenia.

The study presents for the first time the blood level of glutamate and aspartate in schizophrenic patients and in normal subjects in Bangladeshi population. The serum level of glutamate and aspartate were measured in thirty newly diagnosed schizophrenic patients and the same number of subjects matching age was taken from non-schizophrenic control. The age group of the patient was between 15 and 45 years and the male female ratio was 2.7:1. Serum concentration of glutamate (598.83 +/- 574.48 nmol/ml) was significantly higher (p < 0.001) in schizophrenic group compared to control (196.16 +/- 171.31 nmol/ ml). The serum asparate concentration was also significantly higher in schizophrenic cases (282.91 +/- 299.94 nmol/ml) as compared to control (33.89 +/- 42.68 nmol/ml, p < 0.001). The correlation coefficient between serum glutamate and asparate was significant (p < 0.001). The increased serum glutamate and asparate levels may be the causative or contributing factor in the pathogenesis and progression of schizophrenia.

Functional recovery of the spinal cord following ischemia and reperfusion injury.

OBJECTIVE: To study the changes of excitatory amino acids (EAAs) and intracellular calcium ([Ca2+]i), and the protective effect of EAAs receptor antagonists in the tissues of rabbit lumbar spinal cord after 40-minues ischemia and 4-hours reperfusion. METHODS: Thirty healthy rabbits were divided into six groups: sham-operation, 40-minues ischemia, 4-hour reperfusion, ketamine and MgSO4 treatment, ketamine treatment, and saline treatment groups. The contents of EAAs (glutamate and aspartate) and [Ca2+]i were measured. RESULTS: The contents of glutamate and aspartate were decreased to 15.18 micromol/g+/-2.33 micromol/g and 9.99 micromol/g+/-0.69 micromol/g, respectively; 13.75 micromol/g+/-2.58 micromol/g and 6.49 micromol/g+/-1.39 micromol/g after reperfusion. In the ischemia group, the [Ca2+]i was elevated to 221.2 microg/g+/-4.27 microg/g, and elevated further to 298.3 microg/g+/-9.26 microg/g after reperfusion, being significantly higher than that of ischemia and control groups. Ketamine could obviously increase the level of glutamate and aspartate and decrease the level of [Ca2+]i during the ischemia and reperfusion injury. CONCLUSIONS: The excitotoxicity of EAAs and the overload of calcium induced by EAAs play a harmful role in ischemia and reperfusion injury. Ketamine has an effective inhibitory effect.

Contribution of excitatory amino acids to hypoglycemic counter-regulation.

We determined the contribution of central N-methyl-D-aspartate (NMDA) receptor activation to the neuro-endocrine counter-regulatory response to insulin-induced hypoglycemia. Glucose kinetics, gluconeogenic substrate balance and counter-regulatory hormonal responses were determined in two groups of conscious dogs fitted with chronic vascular catheters and intracerebroventricular (i.c.v.) cannula. Peripheral insulin infusion (5 mU/kg per min for 3 h) decreased plasma glucose levels 40% and increased the rate of glucose appearance (R(a)) 2-fold. This was associated with significant increases in net hepatic uptake of glycerol and lactate, without any change in the net hepatic uptake of alanine. i.c.v. pretreatment with MK-801, an NMDA receptor antagonist, blunted (50%) the rise in glucose R(a) as well as the increase in the net hepatic uptake of glycerol and lactate. Hypoglycemia increased plasma cortisol (3-fold to 14.3+/-1 mg/dl) and epinephrine levels (14-fold to 3811+/-172 pg/ml), and this stress response was attenuated (30% and 60%, respectively) by MK-801 pretreatment. In controls, MK-801 did not alter the increase in norepinephrine or glucagon elicited by hypoglycemia. These results indicate that during hypoglycemia, central excitatory amino acids contribute to the modulation of the glucoregulatory response through activation of NMDA receptors, resulting in stimulation of the sympathoadrenal and hypothalamic-pituitary adrenal axis. This mechanism appears to play an important role in the sustained elevation in hepatic glucose production during hypoglycemia.

Increased cerebrospinal fluid glycine: a biochemical marker for a leukoencephalopathy with vanishing white matter.

Recently, a new disease entity has been defined: the disease of vanishing white matter. This leukoencephalopathy has an autosomal-recessive mode of inheritance. No cause or biochemical marker is known. We studied cerebrospinal fluid amino acids in five patients with the disease and found a consistent, moderate elevation of cerebrospinal fluid glycine in all. The ratio of cerebrospinal fluid to plasma glycine was elevated in four patients, in two patients reaching the level considered diagnostic for nonketotic hyperglycinemia. The activity of the glycine cleavage system was found to be normal in lymphoblasts in two patients. The elevation of cerebrospinal fluid glycine in the disease of vanishing white matter is either caused by a primary disturbance of glycine metabolism or is secondary to excitotoxic brain damage.

Amino acids acting as transmitters in amyotrophic lateral sclerosis (ALS).

OBJECTIVES: In amyotrophic lateral sclerosis (ALS), a neurodegenerative disease of unknown origin, excitotoxic mechanisms are supposed to be involved. Divergent results are, however, presented either because of the heterogeneity of this disease, and/or different methodologies used to evaluate the excitotoxic amino acids content. The results of the most sensitive high performance liquid chromatography (HPLC) techniques with precolumn derivatization of fasting serum and CSF glutamate, aspartate, glycine and gamma-aminobutyric acid (GABA) in mild and severely progressing ALS cases are presented here. MATERIAL AND METHODS: We studied 25 ALS patients with different course of the disease and controls, which consisted of 10 cases with other motor neuron diseases and 20 healthy, age-matched subjects. RESULTS: In the ALS patients with a mild course of the disease serum glutamate and aspartate content was either normal or slightly decreased, in all of these cases a rise in GABA and glycine was present. In the severely progressing ALS cases serum glutamate and aspartate was increased. The GABA content was either normal or increased, the glycine level appeared to be either normal or decreased. In CSF the amino acids changes in ALS were less pronounced as compared to serum. The most frequent finding was the increase in GABA concentration both in the mild and the severely progressing group. CSF glutamate in ALS patients with mild course of the disease was decreased, in the severely progressing cases the glutamate level appeared in a broad range from decreased to increased values. CSF aspartate was either normal or elevated, glycine values were present in a broad range from decreased to increased values. In the other tested motor neuron diseases no consistent changes in serum and CSF amino acids concentration was observed. CONCLUSIONS: The data from serum and CSF indicate that in ALS an imbalance between excitatory and inhibitory amino acids might be present in the brain, which may be induced in different ways in particular ALS patients. It may be an important factor for the mediation of neurons death.

Serum levels of excitatory amino acids, serine, glycine, histidine, threonine, taurine, alanine and arginine in treatment-resistant depression: modulation by treatment with antidepressants and prediction of clinical responsivity.

Previous research has revealed that major depression is accompanied by disorders in excitatory amino acids, e.g. glutamate and aspartate, and alterations in serum levels of other amino acids, e.g. serine, glycine and taurine. The aim of the present study was to examine serum levels of aspartate, asparagine, glutamate, glutamine, serine, glycine, threonine, histidine, alanine, taurine and arginine in major depression patients with treatment-resistant depression (TRD). No significant differences in the serum concentrations of any of the above amino acids could be found between patients with and without TRD and normal controls. Non-responders to treatment with antidepressants during a period of 5 weeks were characterized by significantly lower serum levels of aspartate, asparagine, serine, threonine and taurine. A 5-week period of treatment with antidepressants significantly reduced the serum levels of aspartate, glutamate and taurine, and significantly increased the serum concentrations of glutamine. The results suggest that alterations in serum levels of aspartate, asparagine, serine, threonine and taurine may predict the subsequent response to treatment with antidepressants, and that the latter may modulate serum levels of excitatory amino acids and taurine.

Plasma levels of neuroexcitatory amino acids in patients with migraine or tension headache.

Plasma amino acids were analysed in patients with migraine with (9) and without (80) aura, in patients with tension headache (14) and in controls (62). The neuroexcitatory amino acids glutamic acid, glutamine, glycine, cysteic acid and homocysteic acid were elevated in migraine patients while total thiols (cysteine/cystine) were reduced. Patients with tension headache had values which were similar to those of controls. Tryptophan was elevated in migraine patients without aura only. Studies on two patients showed that the raised resting excitatory amino acid levels became still further elevated during a migraine attack. These results show that high concentrations of neurotransmitter amino acids occur normally in migraine patients and suggest that this profile may be a contributory factor in migraine attacks. Tension headache, however, has different biochemical parameters.

Progression of ischaemic stroke and excitotoxic aminoacids.

BACKGROUND: Mechanisms involved in progression of stroke are little understood. Studies in animals have shown an association between neuronal death mediated by excitatory aminoacids and deterioration in focal cerebral ischaemia. We looked for an association between concentrations of glutamate and glycine in plasma and cerebrospinal fluid (CSF) and early progression in a prospective study of 128 patients with acute ischaemic stroke. METHODS: Of 556 consecutive admissions to our emergency unit, 128 eligible patients with ischaemic stroke were included in our study. Blood and CSF samples were taken within the first 24 h from stroke onset when cerebral oedema had been excluded on a previous cranial computed tomography. Ischaemic stroke was judged to be in progression if the Canadian stroke scale score (1.5 = maximum neurological deficit, 10 = no deficit) fell by 1 or more points during the first 48 h after inclusion. Glutamate and glycine concentrations in plasma and CSF were measured by high-performance liquid chromatography. The effect of plasma and CSF glutamate concentrations on progression was analysed by logistic regression. FINDINGS: 43 (33.6%) patients had progressing ischaemic stroke. Concentrations of glutamate and glycine in plasma and CSF were higher in patients with progressing stroke than in those with stable cerebral infarcts (p < 0.0001). There was a significant linear correlation between CSF and plasma concentrations of glutamate (r = 0.79, p < 0.001). The positive predictive value of a plasma glutamate concentration of more than 200 mumol/L for progression of ischaemic stroke was 97% (95% CI 85-100). Glutamate concentrations of more than 200 mumol/L in plasma and of more than 8.2 mumol/L in CSF were independently and significantly associated with progression of neurological deficit (26.1 [6.9-98.6] and 40.9 [7.6-220], respectively). INTERPRETATION: Early neurological progression of acute ischaemic stroke is associated with high concentrations of glutamate in blood and CSF. Measurement of plasma glutamate may be useful for the early detection of those patients with acute stroke who will deteriorate during 48 h after onset.

Neuroexcitatory amino acids and their relation to infarct size and neurological deficit in ischemic stroke.

BACKGROUND AND PURPOSE: The participation of excitatory amino acids (EAAs) in the pathogenesis of ischemic neuronal lesion has been experimentally demonstrated, but clinical experience is scarce. Our objective was to examine EAA levels during the acute phase of cerebral infarction in relation to infarct size and intensity of neurological deficit. METHODS: Using high-performance liquid chromatography, we determined the glutamate, aspartate, taurine, and glycine concentrations in the plasma and cerebrospinal fluid (CSF) of 128 patients with ischemic cerebral infarction confirmed by CT and 43 control subjects. Blood and CSF samples were obtained on admission within the first 24 hours from symptom onset. The severity of the neurological deficit was assessed with the Canadian Stroke Scale immediately after these tests and at 48 hours after inclusion in the study. Infarct volume was determined in a second CT performed between the 4th and 7th day after the patient's inclusion. RESULTS: The concentration of plasmatic glutamate was 121.39 +/- 80.89 mumol/L in the control group and 163.71 +/- 103.13 mumol/L in the patient group (P = .015); in CSF it was 3.46 +/- 1.20 mumol/L in control subjects and 6.55 +/- 4.65 mumol/L in patients (P < .0001). The concentration of glycine in plasma was 158.02 +/- 32.15 mumol/L in control subjects and 189.37 +/- 74.04 mumol/L in patients (P = .007); in CSF it was 6.18 +/- 2.28 mumol/L in control subjects and 11.23 +/- 6.96 mumol/L in patients (P < .0001). The concentrations of glutamate in plasma and in CSF were significantly higher in patients with large cerebral infarcts and in those with cortical infarcts. Levels of glutamate and glycine in plasma and CSF were significantly higher in patients with a higher degree of neurological deficit. CONCLUSIONS: Our results support the excitotoxic activity of glutamate and glycine in patients with cerebral infarction.

Plasma excitatory amino acids in autism.

Plasma amino acid levels were measured by high pressure liquid chromatography (HPLC) in fourteen autistic children, all below 10 years of age. Mean glutamic and aspartic acid valued were elevated (169 +/- 142 uM and 22.1 +/- 13 uM respectively) together with taurine (90.1 +/- 78.7 uM) (p > 0.1). All affected children had low levels of glutamine (241 +/- 166 uM; p < 0.01) and asparagine (22.9 +/- 12.9 uM; p < 0.01) as compared to normal values (585 +/- 25 and 59.2 +/- 4.2 uM respectively); eleven children had increased aspartic acid and eight children had high levels of glutamate; seven of these children had a concomitant increment of taurine. The increment of the three above mentioned compounds was observed at the same time only in five children. These findings demonstrate that abnormal plasmatic levels of neurotransmitter amino acids may be found in some autistic children. Increased glutamatemia may be dietary in origin or may arise endogenously for several reasons, among others, metabolic derrangements in glutamate metabolism perhaps involving vitamin B6, defects or blockage of the glutamate receptor at the neuronal compartment, or alterations in the function of the neurotransmitters transporters. Increments of taurine, an inhibitor, is likely compensatory and calcium dependent.

Amino acid transmitters in patients with headache during the acute phase of cerebrovascular ischemic disease.

BACKGROUND AND PURPOSE: The pathophysiology of headache occurring at stroke onset is unknown. Migraine and ischemia share an excessive release of neuroexcitatory amino acids. Inhibitory amino acids also may be implicated in both diseases. We investigated whether fluctuations of these amino acids occur in headache accompanying cerebral infarction. METHODS: We studied 100 patients with infarction in the territory of the middle cerebral artery. Neurological impairment was assessed using the Canadian Neurological Scale and Barthel Index. Size of infarction was determined with CT. Twenty-eight patients developed headache. Glutamate, aspartate, and taurine were quantified in blood and cerebrospinal fluid (CSF) within 24 hours of stroke onset with cationic exchange chromatography. RESULTS: Stroke subtypes, size of infarct on CT, and clinical scales were similar in patients with and without headache. Plasma glutamate level was 321.14 +/- 149.53 mumol/L in patients with headache and 233 +/- 107.23 mumol/L in those without headache (P < .005). Glutamate in CSF was higher in patients with headache (4.6 +/- 1.49 mumol/L) than in patients without headache (3.11 +/- 1.18 mumol/L) (P < .001). Aspartate concentrations in plasma and CSF were similar in both groups. Taurine concentrations in plasma were 103.10 +/- 52.82 mumol/L and 177.49 +/- 90.92 mumol/L in headache and nonheadache patients, respectively (P < .001). Taurine levels in CSF were 5.42 +/- 2.42 mumol/L in patients with headache and 9.27 +/- 5.31 mumol/L in those without headache (P < .001). No significant correlation was found between amino acid levels in plasma or CSF and size of infarction. CONCLUSIONS: Amino acid neurotransmitters play a role in the pathophysiology of headache that occurs at the onset of stroke. The ischemic penumbral area, more than the infarction itself, may cause a state of cortical hyperexcitability that would be responsible for the cortical release of amino acids and the induction of headache by altering pain perception mechanisms.

Plasma concentrations of excitatory amino acids, serine, glycine, taurine and histidine in major depression.

This study was carried out to investigate plasma levels of excitatory amino acids, such as glutamate and aspartate, and glutamine, serine, glycine, taurine and histidine in major depression. The plasma amino acids were determined by means of HPLC in 22 normal controls and 25 unmedicated patients with major depression. Major depression was characterized by higher plasma taurine levels than normal controls. Significantly lower plasma glycine values and a higher serine/glycine ratio were observed in the depressed group. No significant differences in glutamine, histidine, serine or aspartate levels could be detected between the study groups. By means of linear discriminant analysis, a highly significant separation between major depressed subjects and normal volunteers was found using glycine, glutamate and taurine as discriminatory variables. No significant relationships between any of the amino acids and severity of depression could be found. The results suggest that major depression is accompanied by perturbations in the serine/glycine ratio, excitatory amino acids, such as glutamate, and inhibitory amino acids, such as taurine.