Cerebrospinal Fluid Glutamate Research Articles

L-ornithine-L-aspartate in experimental portal-systemic encephalopathy: therapeutic efficacy and mechanism of action.

Strategies aimed at the lowering of blood ammonia remain the treatment of choice in portal-systemic encephalopathy (PSE). L-ornithine-L-aspartate (OA) has recently been shown to be effective in the prevention of ammonia-precipitated coma in humans with PSE. These findings prompted the study of mechanisms of the protective effect of OA in portacaval-shunted rats in which reversible coma was precipitated by ammonium acetate administration (3.85 mmol/kg i.p.). OA infusions (300 mg/kg/h, i.v) offered complete protection in 12/12 animals compared to 0/12 saline-infused controls. This protective effect was accompanied by significant reductions of blood ammonia, concomitant increases of urea production and significant increases in blood and cerebrospinal fluid (CSF) glutamate and glutamine. Increased CSF concentrations of leucine and alanine also accompanied the protective effect of OA. These findings demonstrate the therapeutic efficacy of OA in the prevention of ammonia-precipitated coma in portacaval-shunted rats and suggest that this protective effect is both peripherally-mediated (increased urea and glutamine synthesis) and centrally-mediated (increased glutamine synthesis).

Neurotransmitters in cerebrospinal fluid reflect pathological activity.

The excitatory transmitters glutamate and aspartate become toxic whenever their extracellular levels are increased because of neuronal, glial and endothelial impairment. Taurine, a volume-regulating amino acid, is released upon excitotoxin-induced cell swelling. Our aim was to investigate if glutamate and aspartate in cerebrospinal fluid (CSF) reveal neuropathology in neurological patients, and if taurine unmasks glutamate-mediated toxicity. Glutamate and aspartate are doubled in viral meningitis, acute multiple sclerosis (MS) and myelopathy compared with control subjects and patients with peripheral facial nerve palsy. These levels do not coincide with a disturbed blood-brain barrier, as estimated by the albumin ratio, are independent of their precursors (glutamine, asparagine) and are not associated with cell lysis. Taurine is significantly increased in meningitis, acute MS, and myelopathy, suggesting glutamate-mediated toxicity. Analysis of transmitters in lumbar CSF can be used to identify patients with cerebral and spinal pathology who might benefit from specific receptor-modulating agents.

Cerebrospinal fluid hypoxanthine, xanthine and uric acid levels may reflect glutamate-mediated excitotoxicity in different neurological diseases

Glutamate-mediated excitotoxicity is associated with adenosine triphosphate (ATP) degradation and generation of oxygen radicals. Hypoxanthine and lactate depict energetic impairment, while xanthine and uric acid reflect activity of radical producing xanthine oxidase. Cerebrospinal fluid (CSF) glutamate, hypoxanthine, lactate, xanthine, and uric acid were investigated in neurological patients. In multiple sclerosis, myelopathy, stroke, epilepsy and viral meningitis glutamate, hypoxanthine, xanthine, and uric acid are increased 2–3-fold compared to controls. Lactate is only elevated in meningitis. Normal lactate dehydrogenase (LDH) levels and absent correlation between the albumin ratio and neurochemical parameters exclude an artificial increase due to cell lysis and barrier damage. Absent correlation between neurochemical parameters within each patient group is most likely related to preserved glial and neuronal uptake mechanisms. CSF hypoxanthine, xanthine, and uric acid levels appear superior to lactate in reflecting glutamate-mediated excitotoxicity in neurological patients.

Changes in the concentration of amino acids in serum and cerebrospinal fluid of patients with Parkinson's disease

The concentrations of sixteen amino acids have been measured in the serum and cerebrospinal fluid (CSF) of patients with Parkinson's disease and compared with those of control subjects. The levels of most amino acids were not different between the two groups, but the level of glutamate in CSF was decreased significantly, while the level of glutamine was increased. The results may be consistent with an alteration of glutamate neurotransmission in Parkinson's disease.

Effect of carbon dioxide on cerebral metabolism during hypoxia-ischemia in the immature rat.

We previously have demonstrated that hypocapnia aggravates and hypercapnia protects the immature rat from hypoxic-ischemic brain damage. To ascertain cerebral blood flow (CBF) and metabolic correlates, 7-d postnatal rats were subjected to hypoxia-ischemia during which they were rendered either hypo-(3.5 kPa), normo- (5.1 kPa), or hypercapnic (7.3 kPa) by the inhalation of either 0, 3, or 6% CO2, 8% O2, balance N2. CBF during hypoxia-ischemia was better preserved in the normo- and hypercapnic rat pups; these animals also exhibited a stimulation of cerebral glucose utilization. Brain glucose concentrations were higher and lactate lower in the normo- and hypercapnic animals, indicating that glucose was consumed oxidatively in these groups rather than by anaerobic glycolysis, as apparently occurred in the hypocapnic animals. ATP and phosphocreatine were better preserved in the normo- and hypercapnic rats compared with the hypocapnic animals. Cerebrospinal fluid glutamate, as a reflection of the brain extracellular fluid concentration, was lowest in the hypercapnic rats at 2 h of hypoxia-ischemia. The data indicate that during hypoxia-ischemia in the immature rat, CBF is better preserved during normo- and hypercapnia; the greater oxygen delivery promotes cerebral glucose utilization and oxidative metabolism for optimal maintenance of tissue high energy phosphate reserves. An inhibition of glutamate secretion into the synaptic cleft and its attenuation of N-methyl-D-aspartate receptor activation would further protect the hypercapnic animal from hypoxic-ischemic brain damage.

Elevated Cerebrospinal Fluid Glutamate in Patients With HIV-related Dementia

Elevated Cerebrospinal Fluid Glutamate in Patients With HIV-related Dementia

Elevated Cerebrospinal Fluid Glutamate in Patients With HIV-related Dementia-Reply

In Reply. —Drs Gurwitz and Kloog raise some points regarding possible alternative interpretations of our data. Human immunodeficiency virus—related encephalitis is present in all patients with AIDS-related dementia, and its severity is correlated with the extent of viral infection and degree of dementia. 1 For this reason, we believe that an increased glutamate level in CSF can be directly explained by interaction of viral proteins or factors from virus-infected cells (cytokines, free radicals, and nitric oxide) with glutamate transporters within the central nervous system. The alternative explanation of increased CSF glutamate levels as a reflection of elevated plasma levels appears less likely, for several reasons. Plasma glutamate levels were similarly elevated in AIDS patients with and without dementia, 2 and BBB disruption also may be present in nondemented HIV-positive patients who have normal CSF glutamate levels. 3 Moreover, although glutamate levels are normally 10 times higher in blood than in CSF, in

Memantine, a noncompetitive NMDA receptor antagonist improves hyperammonemia-induced encephalopathy and acute hepatic encephalopathy in rats.

The aim of this study was to investigate the possible role of N-methyl-D-aspartate (NMDA)-receptor overactivity in two different experimental rat models of encephalopathy: subacute encephalopathy caused by severe hyperammonemia in portacaval-shunted rats (AI-PCS rats) and acute hepatic encephalopathy caused by complete liver ischemia (LIS rats). The effect of the noncompetitive NMDA-receptor antagonist memantine (intraperitoneal [i.p.] 10-20 mg/kg bw or intravenous [i.v.] 5 mg/kg bw) was studied on the severity of encephalopathy by assessment of clinical grading and electroencephalogram (EEG) spectral analysis, on plasma ammonia concentrations, amino acid concentrations in cerebrospinal fluid (CSF), intracranial pressure (ICP), and brain water content. Both rat models developed encephalopathy within 3 to 6 hours, associated with increased CSF glutamate and aspartate concentrations and increased ICP and brain water content. Memantine administration in AI-PCS and LIS rats resulted in a significant improvement in clinical grading and less slowing of EEG activity (P < .05), and smaller increases in CSF glutamate (P < .05) concentrations. Moreover, ICP and brain water content were significantly lower in memantine-treated AI-PCS rats than in untreated AI-PCS rats (P < .05). Memantine had no significant effect on ICP and brain water content in LIS rats, and on ammonia concentrations in both models. These results indicate that NMDA-receptor activation might be involved in the pathogenesis of hyperammonemia-induced encephalopathy and of acute hepatic encephalopathy caused by LIS.

Duration of glutamate release after acute ischemic stroke.

High levels of glutamate in plasma and cerebrospinal fluid (CSF) have been demonstrated in patients with acute ischemic stroke. The duration of this excitatory amino acid release has not been studied, and therefore the window of opportunity of treatment with glutamate antagonists is unknown. The aim of this investigation was to study the duration of the glutamate increase in patients with stable and progressing ischemic stroke. Glutamate in CSF was measured by high-performance liquid chromatography in 184 patients with an acute cerebral infarction of less than 24 hours' duration and in 43 control subjects. Among the 120 patients with stable ischemic stroke, median glutamate levels were significantly lower- and within the reference range of control subjects-in those patients studied 6 to 24 hours from onset of symptoms than in patients studied in the first 6 hours (3 [range, 2 to 10] versus 5 mumol/L [range, 2 to 17]; P < .0001). In 64 patients with progressing ischemic stroke, glutamate concentrations measured at any time interval during the first 24 hours from onset were significantly higher than in the stable stroke and control groups. The presence of glutamate increase in the CSF cannot be documented for greater than 6 hours in stable ischemic stroke. The sustained elevation of glutamate observed in progressing stroke suggests that the window to prevent neurological deterioration may be wider.

Effects of I.C.V. administration of ethylcholine aziridinium (AF64A) on the central glutamatergic nervous systems in rats

Changes in glutamatergic nervous activities following intracerebroventricular (icv) administration of ethylcholine aziridinium (AF64A) were studied in rats. The levels of total glutamate, those of glutamate in cerebrospinal fluid (CSF) and in extracellular fluid (ECF) of striatum, the activities of glutamine synthetase (GS), glutaminase and glutamate dehydrogenase (GDH) and the specific binding sites of [(3)H]MK801 in striatum, hippocampus and frontal cortex were assessed a week after the infusion of AF64A (3 nmol) into lateral ventricle. The levels of total glutamate were significantly decreased in striatum, hippocampus and frontal cortex after AF64A treatment. Although the levels of glutamate in CSF weren't changed after AF64A treatment, the levels of glutamate in ECF of striatum were significantly decreased (62.6%). GS activities in striatum were significantly decreased. But, glutaminase activities in striatum were significantly increased. However, the activities of GS and glutaminase in frontal cortex and hippocampus weren't changed. Although GDH activities in frontal cortex were significantly decreased, those in striatum and hippocampus weren't altered. The striatal densities of [(3)H]MK 801 binding sites were increased without changes in its affinity. Also, the specific binding sites of [(3)H]MK801 were increased in frontal cortex but not in hippocampus. These results indicate that the glutamatergic nervous activities were altered with the infusion of AF64A into lateral ventricle. Furthermore, it suggest that the decreased levels of glutamate after AF64A treatment may affect the change in the other parameters of glutamatergic neuronal activities.

Progression of ischaemic stroke and excitotoxic aminoacids

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. 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. 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). 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.

The effect of glucose during ischemia on brain ATP, lactate, and glutamate in piglets.

Glucose worsens hypoxic-ischemic brain injury in 0- to 3-day-old piglets. Piglets were randomly assigned to have blood glucose increased with glucose infusion (n = 12), or decreased with insulin (n = 13), or a sham group (n = 10). In the insulin and glucose groups at time 0, both carotid arteries were clamped, and blood was withdrawn to reduce the blood pressure one third. At time 15 min FiO2 was reduced to 6%. At time 30 min cerebrospinal fluid (CSF) was taken for glutamate, and the brains were frozen. The shams had CSF removed and brains frozen without hypoxia or ischemia. Brain ATP was 1.7 +/- 0.09 mumol/g wet weight in the shams, 0.98 +/- 0.09 in the glucose group (p < 0.01 vs. sham), and 0.52 +/- 0.10 in the insulin group (p < 0.01 vs. glucose). Brain lactate levels were 4.3 +/- 1.0 mumol/g wet weight in the shams, 18.3 +/- 1.9 in the insulin group (p < 0.01 vs. sham), and 29.4 +/- 2.6 in the glucose group (p < 0.01 vs. insulin). CSF glutamate was 9.3 +/- 3.6 microM in the glucose group, 9.6 +/- 3.5 in the insulin group, and 2.2 +/- 0.9 in the shams (p < 0.05, glucose and insulin > sham). The Bmax for MK-801 binding was 2.3 +/- 0.2 pmol/mg protein in the glucose group, 2.6 +/- 0.1 in the insulin group (p < 0.05 vs. sham), and 2.0 +/- 0.2 in the shams, and the Kd was the same in the three groups (p = nonsignificant). Brain Na+,K(+)-ATPase was the same in the three groups (p = nonsignificant). Providing additional glucose preserves ATP during hypoxic-ischemic brain injury in the piglet but does not change CSF glutamate or brain-801 binding and probably worsens outcome by elevating brain lactate levels above the threshold for cellular injury.

Excitatory Amino Acid Levels in Cerebrospinal Fluids of Epileptic Patients

Epilepsy is among the most neurologic disorders. Due to its damaging effects on the brain and the psychological problems that it creates in the patients, it deserves extensive study of its pathogenesis and new therapeutical approaches. The most widely accepted hypothesis on the pathogenesis of epilepsy is a failure in the regulation of excitatory and inhibitory mechanisms in the brain. The aim of this study was to assess the levels of amino acids in cerebrospinal fluid (CSF) which was believed to reflect the levels of excitatory amino acids in the brain. CSF glutamate, aspartate and glycine levels were determined by gas -liquid chromatography in 12 epileptic patients (juvenile myoclonic epilepsy (JME) n=7, idiopathic primary generalized epilepsy with tonic clonic seizuren=5) and 12 controls. In the epileptic patients, glutamate and glycine levels were significantly higher than controls (p The findings of this study suggest that further studies with a larger patient population and comparison of levels in CSF and epileptogenic brain tissue would be useful for a better understanding of the role excitatory amino acids in the pathogenesis of epilepsy.

High levels of cerebrospinal fluid glutamate in Rett syndrome

Rett syndrome is a neurodevelopmental disease affecting girls. The cause is not known. Roles for trophic factors and excitatory neurotransmitters have beer postulated. To study the significance of excitatory amino acids in Rett syndrome, we determined glutamate and aspartate concentrations in the cerebrospinal fluid from 11 girls with Rett syndrome (age 8 years 4 months ± 5.7 years, mean ± SD) and 11 controls (age 7 ± 4.2 years). In the patients with Rett syndrome, the mean of cerebrospinal fluid glutamate concentration was 355.2 nmol/L (SD ± 109.2 nmol/L). In the controls it was 203.9 nmol/L (SD ± 55.5 nmol/L). In Rett syndrome cases, cerebrospinal fluid glutamate concentrations were significantly higher ( P = 0.0006) than in the controls. In the Rett syndrome group, the mean cerebrospinal fluid aspartate concentration was 119.4 nmol/L (SD ± 43.5 nmol/L). In the control group, it was 90.9 nmol/L (SD ± 20.9 nmol/L). The difference between the cerebrospinal fluid aspartate values was not significant. Glutamate may therefore play an important role in the primary pathogenesis in Rett syndrome. Further investigations are needed, with recognition of possible actions of neuronal growth factors and excitatory neurotransmitters in the damage mechanisms of Rett syndrome.

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

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. 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. 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. Our results support the excitotoxic activity of glutamate and glycine in patients with cerebral infarction.

Tiagabine prevents seizures, neuronal damage and memory impairment in experimental status epilepticus

A novel antiepileptic drug, tiagabine (( R)-N-[4,4-di-(3-methylthien-2-yl)but-3-enyl] nipecotic acid hydrochloride), was studied in rats in order to determine its efficacy in preventing seizures, seizure-induced neuronal damage and impairment of spatial memory in the perforant pathway stimulation model of status epilepticus. In pilot experiments, administration of tiagabine (50, 100 or 200 mg/kg/day) with subcutaneously implanted Alzet osmotic pumps led to a dose-dependent increase in tiagabine concentrations in the serum and brain. Two days of tiagabine treatment at a dose range of 50–200 mg/kg/day did not change the levels of γ-aminobutyric acid (GABA), glutamate or aspartate in cisternal cerebrospinal fluid (CSF) compared to the controls. In the pentylenetetrazol test, the maximal anticonvulsive effect of tiagabine administered via osmotic pumps was achieved already with a dose of 50 mg/kg/day. In the perforant pathway model of status epilepticus, subchronic treatment with tiagabine (Alzet pumps, 50 mg/kg/day) completely prevented the appearance of generalized clonic seizures during stimulation ( P < 0.001). In the same rats, tiagabine treatment reduced the loss of pyramidal cells in the CA3c and CA1 fields of the hippocampus ( P < 0.05) but not the loss of somatostatin immunoreactive neurons in the hilus. Two weeks after perforant pathway stimulation, the tiagabine-treated rats performed better in the Morris water-maze test than the vehicle-treated rats did ( P < 0.001). Our results show that tiagabine treatment reduces the severity of seizures in the perforant pathway stimulation model of status epilepticus. Possibly associated with the reduction in seizure number and severity, tiagabine treatment also reduced seizure-induced damage to pyramidal cells in the hippocampus as well as the impairment of the spatial memory associated with hippocampal damage.

Cerebrospinal fluid concentrations of glutamate and GABA during perinatal cerebral hypoxia-ischemia and seizures

Cerebrospinal fluid (CSF) concentrations of glutamate and γ-aminobutyric acid (GABA), as estimates of levels in the extracellular compartment of brain, were determined in 7-day postnatal rats at the terminus of hypoxia-ischemia and during status epilepticus, induced with bicuculline, at 2 and 24 h of recovery. Hypoxia-ischemia was associated with increased CSF glutamate, which was not increased further during status epilepticus. In contrast, CSF GABA was increased by hypoxia-ischemia as well as by status epilepticus during recovery. CSF glutamate/GABA ratios in rat pups subjected to status epilepticus with or without prior hypoxia-ischemia were lower than control animals during recovery. The lack of any significant increase in glutamate or in the glutamate/GABA ratio during status epilepticus would preclude any neuronal injury from occurring in those immature rats sustaining seizures alone or any accentuation of brain damage in those animals subjected to prior cerebral hypoxia-ischemia.

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

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. 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. 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. 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.

Potential Treatment of Amyotrophic Lateral Sclerosis with Gabapentin: A Hypothesis

To provide the biochemical rationale for the use of the new anticonvulsant agent gabapentin as a treatment for amyotrophic lateral sclerosis (ALS). ALS is a neuropathologic disorder of the central nervous system characterized by a progressive loss of upper and lower motor neurons. Although the etiopathology of ALS is incompletely known, it is hypothesized that glutamatergic neurotransmission is related to neuropathology. Glutamate is an excitatory amino acid neurotransmitter that is cytotoxic when overexpressed at synaptic terminals, probably through a calcium-related mechanism. The concentration of glutamate in cerebrospinal fluid is increased in patients with ALS. The increased extracellular concentrations of glutamate may be caused by a decreased capacity of glutamate transport in brain tissue and/or abnormal glutamate metabolism. Recent success with the glutamate release inhibitor riluzole in well-controlled clinical trials supports the excitotoxic mechanism of neuropathology in patients with ALS. POTENTIAL TREATMENT FOR ALS: Gabapentin has demonstrated neuroprotective properties in a model of chronic glutamate toxicity in vitro. Although the neuroprotective mechanism of action of gabapentin is currently unknown, it is hypothesized here that gabapentin decreases the rate of formation of glutamate derived from the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine. The proposed decrease in formation of glutamate from BCAAs may decrease the pool of releasable glutamate and therefore compensate for diminished glutamate uptake capacity and/or abnormal glutamate metabolism in patients with ALS. Based on this rationale, it is proposed that gabapentin may provide a beneficial effect in the treatment of patients with ALS.

Neuron specific enolase in asphyxiated newborns: association with encephalopathy and cerebral function monitor trace.

Neuron specific enolase (NSE) in serum and cerebrospinal fluid (CSF) and glutamate in CSF were investigated in the immediate postasphyctic period in 22 term newborn infants. The cerebral function monitor (CFM) pattern was also assessed and hypoxic-ischaemic encephalopathy (HIE) was graded. NSE was significantly increased in the CSF of infants with HIE (median value 25.4 micrograms/l) compared with control infants (10.0 micrograms/l). Infants with the highest concentrations died. NSE in CSF correlated with the degree of asphyxial damage. Glutamate and NSE in CSF did not correlate, presumably due to the different time factors of the release after the insult. NSE in CSF corresponded well with the type of CFM pattern, which was also highly predictive of outcome.