Blood Glutamate Concentrations Research Articles

The Integrity of the Blood-Brain Barrier as a Critical Factor for Regulating Glutamate Levels in Traumatic Brain Injury.

A healthy blood-brain barrier (BBB) shields the brain from high concentrations of blood glutamate, which can cause neurotoxicity and neurodegeneration. It is believed that traumatic brain injury (TBI) causes long-term BBB disruption, subsequently increasing brain glutamate in the blood, in addition to increased glutamate resulting from the neuronal injury. Here, we investigate the relationship between blood and brain glutamate levels in the context of BBB permeability. Rats exposed to BBB disruption through an osmotic model or TBI and treated with intravenous glutamate or saline were compared to control rats with an intact BBB treated with intravenous glutamate or saline. After BBB disruption and glutamate administration, the concentrations of glutamate in the cerebrospinal fluid and blood and brain tissue were analyzed. The results showed a strong correlation between the brain and blood glutamate concentrations in the groups with BBB disruption. We conclude that a healthy BBB protects the brain from high levels of blood glutamate, and the permeability of the BBB is a vital component in regulating levels of glutamate in the brain. These findings bring a new approach to treating the consequences of TBI and other diseases where long-term disruption of the BBB is the central mechanism of their development.

Abstract 218: Novel Blood Biomarker Taurine and Glutamate for Early Predicting Outcomes After Out-of-hospital Cardiac Arrest

Introduction: Out-of-Hospital cardiac arrest (OHCA) is the leading cause of death with an overall survival rate of less than 10%. Organ failure and metabolic impairment are two critical elements of post-CA syndrome. Taurine and glutamate are amino acids that are expressed primarily in heart and brain. The compensatory release during osmotic stress, as seen in CA, amplifies reperfusion injury, heart stunning and brain edema. Thus, taurine and glutamate concentrations in blood likely reflects the extent of injury in the heart and brain following CA. Hypothesis: Plasma taurine and glutamate concentration correlates with CA outcomes. Methods: Adult OHCA patients (n=37) at an urban academic ED were enrolled from 2018-2019. Among them, 14 were survivors (S) and 23 were nonsurvivors (NS). Blood samples were collected at various time points including the time at hospital arrival, 6, 24, 48, 72 hours after arrival (T0, 6, 24, 48 and 72 h, respectively), and measured. T-test and GEE were used for mean comparison and longitudinal trend analysis, respectively. p < 0.05 was considered as statistically significant. Results: Plasma taurine and glutamate concentrations were compared between S and NS at T0 and across all time points. Both concentrations were significantly higher in NS vs S group at T0 (for taurine: 77.7 ± 40.0 in NS vs. 60.0 ± 31.9 μM in S, p =0.014; for glutamate: 176.4 ± 98.7 in NS vs. 162.8 ± 111.1 μM in S, p =0.0496), and showed a decreasing trend over time. In the first 6 h, taurine and glutamate level decreased more in S group than NS group (over 30% drop in S compared to <15% drop in NS). In addition, a positive correlation of cerebral performance category was seen at T6 with taurine (p=0.0354), but not with glutamate. Conclusions: Blood taurine and glutamate may serve as early biomarkers in predicting OHCA outcomes. Monitoring their change over time can help physicians tailor treatment decisions and patient management.

Blood glutamate scavenging as a novel glutamate-based therapeutic approach for post-stroke depression

Post-stroke depression (PSD) is a major complication of stroke that significantly impacts functional recovery and quality of life. While the exact mechanism of PSD is unknown, recent attention has focused on the association of the glutamatergic system in its etiology and treatment. Minimizing secondary brain damage and neuropsychiatric consequences associated with excess glutamate concentrations is a vital part of stroke management. The blood glutamate scavengers, oxaloacetate and pyruvate, degrade glutamate in the blood to its inactive metabolite, 2-ketoglutarate, by the coenzymes glutamate–oxaloacetate transaminase (GOT) and glutamate–pyruvate transaminase (GPT), respectively. This reduction in blood glutamate concentrations leads to a subsequent shift of glutamate down its concentration gradient from the blood to the brain, thereby decreasing brain glutamate levels. Although there are not yet any human trials that support blood glutamate scavengers for clinical use, there is increasing evidence from animal research of their efficacy as a promising new therapeutic approach for PSD. In this review, we present recent evidence in the literature of the potential therapeutic benefits of blood glutamate scavengers for reducing PSD and other related neuropsychiatric conditions. The evidence reviewed here should be useful in guiding future clinical trials.

Neuroprotection mediated by remote preconditioning is associated with a decrease in systemic oxidative stress and changes in brain and blood glutamate concentration

It has been shown that ischemia of remote organs can generate resistance to ischemic conditions within sensitive brain tissues. However, only limited information about its mechanism is available. In the present paper, we used hind-limb ischemia by tourniquet to generate early remote ischemic tolerance in rats. The main objective was to investigate the role of glutamate in the process of neuroprotection and discover parameters that are affected in the blood of ischemia-affected animals. Our results showed that pretreatment with a hind-limb tourniquet caused a decrease in neurodegeneration by about 30%. However, we did not observe neurological deficit recovery. When compared to ischemia, glutamate concentration decreased in all observed brain regions (cortex, CA1 and dentate gyrus of hippocampus), regardless of their sensitivity to blood restrictions. In contrast to this, the blood levels raised significantly from 26% to 29% during the first four days of postischemic reperfusion. Pretreatment of animals reduced systemic oxidative stress—as represented by lymphocytic DNA damage—by about 80%, while changes in blood antioxidant enzymes (catalase, superoxide dismutase) were not detected.With these data we can further hypothesize that hind-limb-tourniquet preconditioning could accelerate brain-to-blood efflux of glutamate which could positively impact neuronal survival of ischemia-affected brain regions. Moreover, remote preconditioning improved systemic oxidative stress and did not seem to be affected by enzymatic antioxidant defenses in the blood.

Reduction in Blood Glutamate Levels Combined With the Genetic Inactivation of A2AR Significantly Alleviate Traumatic Brain Injury-Induced Acute Lung Injury.

Traumatic brain injury-induced acute lung injury (TBI-ALI) is a serious complication of traumatic brain injury (TBI). Our previous clinical study found that high levels of blood glutamate after TBI were closely related to the occurrence and severity of TBI-ALI, while it remains unknown whether a high concentration of blood glutamate directly causes or aggravates TBI-ALI. We found that inhibition of the adenosine A2A receptor (A2AR) after brain injury alleviated the TBI-ALI; however, it is unknown whether lowering blood glutamate levels in combination with inhibiting the A2AR would lead to better effects. Using mouse models of moderate and severe TBI, we found that intravenous administration of L-glutamate greatly increased the lung water content, lung-body index, level of inflammatory markers in bronchoalveolar lavage fluid and acute lung injury score and significantly decreased the PaO2/FiO2 ratio. Moreover, the incidence of TBI-ALI and the mortality rate were significantly increased, and the combined administration of A2AR activator and exogenous glutamate further exacerbated the above damaging effects. Conversely, lowering the blood glutamate level through peritoneal dialysis or intravenous administration of oxaloacetate notably improved the above parameters, and a further improvement was seen with concurrent A2AR genetic inactivation. These data suggest that A2AR activation aggravates the damaging effect of high blood glutamate concentrations on the lung and that combined treatment targeting both A2AR and blood glutamate may be an effective way to prevent and treat TBI-ALI.

Decreased Glycaemia with Renal Failure in Diabetes Betides in Relation to the Change in Renal Glutamate Metabolism

A reduction in renal gluconeogenesis appears to be one cause for the drop in blood glucose concentration (BGC) accompanying decreased renal function in diabetes. However, it remains unclear as to how this drop in BGC is related to the changes in reabsorption of amino acids (AAs) that accompany decreased renal function. We therefore investigated the relationship between the drop in BGC accompanying decreased renal function in diabetes patients and changes in the reabsorption rates of AAs. Subjects and methods: Using 100 diabetes patients and 100 non-diabetics as subjects, we measured their blood AAs concentration and urinary AAs excretion, and calculated the AAs’ reabsorption rate. We then examined the relationship between the latter and the estimated glomerular filtration rate (eGFR) and HbA1c. Results: In diabetics, blood glutamate concentration and reabsorption rate of glutamate were reduced. The blood glutamine concentration was increased; however, the reabsorption of glutamine was unchanged. The reabsorption rates of some AAs, including glutamate, showed a positive correlation with eGFR. However, a reduced reabsorption rate of glutamate was the only independent risk factor for reduced eGFR. Moreover, only the reabsorption rate of glutamate correlated positively with HbA1c. Conclusions: In diabetes, glutamate reabsorption shows a decline that parallels decreased renal function: this reduction is related to a drop in BGC. The reduction in the reabsorption of glutamate appears to influence renal gluconeogenesis by reducing the gluconeogenesis-adjusting factor (malate-aspartate shuttle), not by reducing gluconeogenic substrates. Further studies are therefore needed to examine the role glutamate plays in renal gluconeogenesis.

Dramatic increases in blood glutamate concentrations are closely related to traumatic brain injury-induced acute lung injury

Traumatic brain injury-induced acute lung injury (TBI-ALI) is a serious complication after brain injury for which predictive factors are lacking. In this study, we found significantly elevated blood glutamate concentrations in patients with TBI or multiple peripheral trauma (MPT), and patients with more severe injuries showed higher blood glutamate concentrations and longer durations of elevated levels. Although the increase in amplitude was similar between the two groups, the duration was longer in the patients with TBI. There were no significant differences in blood glutamate concentrations in the patients with MPT with regard to ALI status, but the blood glutamate levels were significantly higher in the patients with TBI-ALI than in those without ALI. Moreover, compared to patients without ALI, patients with TBI showed a clearly enhanced inflammatory response that was closely correlated with the blood glutamate levels. The blood glutamate concentration was also found to be a risk factor (adjusted odds ratio, 2.229; 95% CI, 1.082–2.634) and was a better predictor of TBI-ALI than the Glasgow Coma Scale (GCS) score. These results indicated that dramatically increased blood glutamate concentrations were closely related to the occurrence of TBI-ALI and could be used as a predictive marker for “at-risk” patients.

Glutamate Concentrations in Plasma and CSF in Patients with Glioma and Meningioma

Objectives: Glioma, a malignant intra-axial brain tumor, can release glutamate that facilitates tumor expansion, stimulates tumor-cell proliferation and motility and promotes epileptic activity. Glutamate acid is the major excitatory neurotransmitter in the mammalian Central Nervous System. We explore correlations of glutamate concentrations in blood and cerebrospinal fluid in patients with glioma in comparison to patients with meningioma which is the most common benign cerebral tumor. Experimental design: Samples from 16 patients with glioma and 13 patients with meningioma were analyzed. Glutamate levels in blood and cerebrospinal fluid were measured by HPLC method. Principal observations: Mean value ± SD of Glu concentration

Impact of plasma transaminase levels on the peripheral blood glutamate levels and memory functions in healthy subjects

Background & aimsBlood aspartate aminotransferase (AST) and alanine transaminase (ALT) levels are the most frequently reliable biomarkers of liver injury. Although AST and ALT play central roles in glutamate production as transaminases, peripheral blood levels of AST and ALT have been regarded only as liver injury biomarkers. Glutamate is a principal excitatory neurotransmitter, which affects memory functions in the brain. In this study, we investigated the impact of blood transaminase levels on blood glutamate concentration and memory. MethodsPsychiatrically, medically, and neurologically healthy subjects (n=514, female/male: 268/246) were enrolled in this study through local advertisements. Plasma amino acids (glutamate, glutamine, glycine, d-serine, and l-serine) were measured using a high performance liquid chromatography system. The five indices, verbal memory, visual memory, general memory, attention/concentration, and delayed recall of the Wechsler Memory Scale-Revised were used to measure memory functions. ResultsBoth plasma AST and ALT had a significant positive correlation with plasma glutamate levels. Plasma AST and ALT levels were significantly negatively correlated with four of five memory functions, and plasma glutamate was significantly negatively correlated with three of five memory functions. Multivariate analyses demonstrated that plasma AST, ALT, and glutamate levels were significantly correlated with memory functions even after adjustment for gender and education. ConclusionsAs far as we know, this is the first report which could demonstrate the impact of blood transaminase levels on blood glutamate concentration and memory functions in human. These findings are important for the interpretation of obesity-induced metabolic syndrome with elevated transaminases and cognitive dysfunction.

Peripheral Glutamate Levels in Schizophrenia: Evidence from a Meta-Analysis

Background: Recent research attempting to develop novel medications has turned to glutamatergic signaling pathways to find effective treatments for symptom clusters of schizophrenia. This meta-analysis was undertaken to clarify whether a difference in peripheral glutamate levels exists between patients with schizophrenia and healthy controls. Methods: The electronic databases Ovid MEDLINE, PubMed, and PsycINFO were systematically searched up to April 2013. The search was limited to case-control studies of blood glutamate levels in schizophrenia written in English. The differences in glutamate levels were evaluated by calculating standardized mean differences (SMD). Results: We found ten studies that met the inclusion criteria for a total of 320 schizophrenia patients and 294 controls. The meta-analysis showed that peripheral glutamate levels in schizophrenia patients were significantly higher overall than in controls (SMD = 0.635, p = 0.004). However, a significant effect of the method used to measure glutamate concentrations was found (F = 7.36, p = 0.01) where fluorometric assay was associated with effect sizes in the opposite direction. Conclusion: A higher blood glutamate concentration was found in patients with schizophrenia. However, given the small sample size and methodological differences among studies, this result is not conclusive. More comprehensive research is needed to understand the relationship between glutamate levels in schizophrenia in the blood and the brain.

Platelet-mediated changes to neuronal glutamate receptor expression at sites of microthrombosis following experimental subarachnoid hemorrhage.

Glutamate is important in the pathogenesis of brain damage after cerebral ischemia and traumatic brain injury. Notably, brain extracellular and cerebrospinal fluid as well as blood glutamate concentrations increase after experimental and clinical trauma. While neurons are one potential source of glutamate, platelets also release glutamate as part of their recruitment and might mediate neuronal damage. This study investigates the hypothesis that platelet microthrombi release glutamate that mediates excitotoxic brain injury and neuron dysfunction after subarachnoid hemorrhage (SAH). The authors used two models, primary neuronal cultures exposed to activated platelets, as well as a whole-animal SAH preparation. Propidium iodide was used to evaluate neuronal viability, and surface glutamate receptor staining was used to evaluate the phenotype of platelet-exposed neurons. The authors demonstrate that thrombin-activated platelet-rich plasma releases glutamate, at concentrations that can exceed 300 μM. When applied to neuronal cultures, this activated plasma is neurotoxic, and the toxicity is attenuated in part by glutamate receptor antagonists. The authors also demonstrate that exposure to thrombin-activated platelets induces marked downregulation of the surface glutamate receptor glutamate receptor 2, a marker of excitotoxicity exposure and a possible mechanism of neuronal dysfunction. Linear regression demonstrated that 7 days after SAH in rats there was a strong correlation between proximity to microthrombi and reduction of surface glutamate receptors. The authors conclude that platelet-mediated microthrombosis contributes to neuronal glutamate receptor dysfunction and might mediate brain injury after SAH.

Brain to blood glutamate scavenging as a novel therapeutic modality: a review

It is well known that abnormally elevated glutamate levels in the brain are associated with secondary brain injury following acute and chronic brain insults. As such, a tight regulation of brain glutamate concentrations is of utmost importance in preventing the neurodegenerative effects of excess glutamate. There has been much effort in recent years to better understand the mechanisms by which glutamate is reduced in the brain to non-toxic concentrations, and in how to safely accelerate these mechanisms. Blood glutamate scavengers such as oxaloacetate, pyruvate, glutamate-oxaloacetate transaminase, and glutamate-pyruvate transaminase have been shown to reduce blood glutamate concentrations, thereby increasing the driving force of the brain to blood glutamate efflux and subsequently reducing brain glutamate levels. In the past decade, blood glutamate scavengers have gained increasing international interest, and its uses have been applied to a wide range of experimental contexts in animal models of traumatic brain injury, ischemic stroke, subarachnoid hemorrhage, epilepsy, migraine, and malignant gliomas. Although glutamate scavengers have not yet been used in humans, there is increasing evidence that their use may provide effective and exciting new therapeutic modalities. Here, we review the laboratory evidence for the use of blood glutamate scavengers. Other experimental neuroprotective treatments thought to scavenge blood glutamate, including estrogen and progesterone, beta-adrenergic activation, hypothermia, insulin and glucagon, and hemodialysis and peritoneal dialysis are also discussed. The evidence reviewed here will hopefully pave the way for future clinical trials.

Yield of Holter and echocardiography in the screening of TIA

oxaloacetate and glutamate to aspartate and α-ketoglutarate. Thus, the increase of the co-substrate (oxaloacetate) shifts the equilibrium of the reaction to the right side, thereby decreasing the blood glutamate concentration and lowering the brain glutamate levels (see [3,4] for review). Based on this mechanism, we have demonstrated that a decrease of blood glutamate levels, by means of an intravenous (i.v.) administration of oxaloacetate, leads to a larger natural glutamate gradient from the brain to the blood, which facilitates the decreases of extracellular levels of brain glutamate inducing a neuroprotective effect after ischemic insults [5,6]. Therefore, the administration of oxaloacetate may represent an interesting strategy to reduce the neurological complications associated to ECC, although further experimental studies are necessary to elucidate this hypothesis. References

The effects of estrogen and progesterone on blood glutamate levels during normal pregnancy in women

The purpose of this study was to examine whether changes in estrogen and progesterone levels observed during normal pregnancy influence blood glutamate levels. One-hundred and sixteen pregnant women were divided into three groups based on gestational age: group 1 included women in their first trimester, group 2 included women in their second trimester, and group 3 included women in their third trimester. A single venous blood sample was collected and analyzed for concentrations of estrogen, progesterone, glutamate-pyruvate transaminase (GPT), glutamate-oxaloacetate transaminase (GOT), and glutamate. Concentrations of blood glutamate were significantly lower during the second trimester (p < 0.001) and third trimester (p < 0.001). Blood glutamate levels were inversely correlated with levels of estrogen and progesterone throughout pregnancy (p < 0.001). Levels of GOT and GPT remained stable during the course of pregnancy, apart from a moderate reduction in GPT during the third trimester. Increases in estrogen and progesterone levels during advanced stages of pregnancy were inversely correlated with maternal blood glutamate concentrations. Once a maximal blood glutamate-reducing effect was achieved, any additional estrogen and progesterone had a negligible effect on blood glutamate. This study demonstrates the glutamate-reducing effects of estrogen and progesterone, which is most likely not mediated by a GOT/GPT conversion mechanism.

The Effects of Peritoneal Dialysis on Blood Glutamate Levels

Previous study has demonstrated the efficacy of hemodialysis in reducing blood glutamate levels. The purpose of the present study is to investigate whether peritoneal dialysis (PD) may be effective in lowering blood glutamate levels, which may serve as a potential tool for improving neurological function after brain injury. Two liters of dialysis solution were infused over 10 minutes into 18 patients with stage V chronic kidney disease. Blood samples were collected immediately before initiation of PD, and hourly for a total of 5 blood samples. Blood samples were sent for determination of glutamate, creatinine, urea, glucose, glutamate oxaloacetate transaminase, and glutamate pyruvate transaminase. PD samples were collected and analyzed for glutamate, creatinine, urea, and glucose at the same time points as the blood samples. Blood glutamate concentrations were significantly reduced by 60 minutes after the infusion of dialysis solution (P<0.0001), whereas levels of glutamate in the dialysis solution were increased significantly by 60 minutes (P<0.0001). We demonstrated that PD is an effective modality in reducing blood glutamate concentrations. This method may be potentially utilized for the treatment of acute and chronic brain disorders that are accompanied by elevated glutamate in the brain's extracellular fluid. Considering the rapid saturation of the PD solution with glutamate, we recommend frequent dwelling of the PD solution in order to maintain low concentrations of blood glutamate.

Neuronal Excitotoxicity after Carotid Angioplasty and Stent Placement Procedures

To investigate if glutamate levels also increase in carotid angioplasty and stent placement (CAS) procedures, since high plasma glutamate levels are associated with ischemic infarction and transient ischemic attacks, but the length of ischemia needed to elicit such elevation has not been assessed. All patients or their relatives signed informed consent. By using high-performance liquid chromatography, plasma glutamate concentrations were determined in 74 patients treated with CAS. Blood samples were obtained with arterial and peripheral venous catheterization before and after the procedure, and venous blood samples were obtained 24, 48, and 72 hours after CAS. Glutamate concentrations were also analyzed in two different control groups: 16 patients without carotid stenosis before and after diagnostic cerebral angiography and 20 patients treated with coronary angioplasty and stent placement. The χ(2) test, t test, and analysis of variance were used to compare glutamate concentrations among the groups. Baseline glutamate concentrations were similar between patients who underwent CAS and both control groups. In CAS patients, glutamate concentrations in venous blood increased immediately after the procedure (354.1 μmol/L ± 132.8) and returned to baseline levels at 24 hours (129.5 μmol/L ± 56.8) (P < .0001). Glutamate concentrations remained unchanged over time in both control groups. A rapid increase in plasma glutamate levels occurs after CAS procedures, unrelated to stroke.

Effects of strong physical exercise on blood glutamate and its metabolite 2-ketoglutarate levels in healthy volunteers.

Excessive concentrations of L-glutamate (glutamate) have been found to posses neurotoxic properties. This study investigates how stress induced by strong physical exercise effects blood glutamate, 2-ketoglutarate, Alanine aminotransferase (ALT) and Aspartate Aminotransferase (AST) levels. The relationship between muscle damage caused by strong physical exercise and blood glutamate levels was also examined. Twenty-two healthy volunteers engaged in intense veloergometry ("spinning") for a duration of 60 minutes. Two 10 minute peaks of extremely intense exercise were performed at 10 minutes and 50 minutes after the start of exercise. After 60 minutes of exercise, volunteers were monitored for an additional 180 minutes in resting conditions. Blood samples for determination of glutamate and 2-ketoglutarate levels were collected prior to exercise and then every 30 min for entire experiment. Blood samples were also taken at those time points to measure glutamate, 2-ketoglutarate, AST, ALT, creatine phosphokinase (CPK), myoglobin, lactate and venous blood gas levels. Blood glutamate levels were significantly elevated throughout the exercise session (P less than 0.001) and then returned to baseline levels at the cessation of exercise. 2-ketoglutarate, a product of glutamate metabolism, reached significantly elevated levels at 30 minutes (P less than 0.01) from the start of exercise and remained elevated up to 240 minutes post exercise initiation (P less than 0.001). AST and ALT levels were elevated at 60 minutes when compared to baseline. AST levels remained elevated at 240 minutes, unlike ALT levels which returned to baseline values at 240 minutes. Strong physical exercise leads to a significant elevation in blood glutamate, most likely as a result of skeletal muscle damage. 2-ketoglutarate was also found to be elevated for long periods of time, reflecting an ongoing process of glutamate breakdown. Elevated concentrations of AST and ALT in plasma reflect the importance of these enzymes in the maintenance of stable blood glutamate concentrations.

Blood Glutamate Scavenging: Insight into Neuroprotection

Brain insults are characterized by a multitude of complex processes, of which glutamate release plays a major role. Deleterious excess of glutamate in the brain’s extracellular fluids stimulates glutamate receptors, which in turn lead to cell swelling, apoptosis, and neuronal death. These exacerbate neurological outcome. Approaches aimed at antagonizing the astrocytic and glial glutamate receptors have failed to demonstrate clinical benefit. Alternatively, eliminating excess glutamate from brain interstitial fluids by making use of the naturally occurring brain-to-blood glutamate efflux has been shown to be effective in various animal studies. This is facilitated by gradient driven transport across brain capillary endothelial glutamate transporters. Blood glutamate scavengers enhance this naturally occurring mechanism by reducing the blood glutamate concentration, thus increasing the rate at which excess glutamate is cleared. Blood glutamate scavenging is achieved by several mechanisms including: catalyzation of the enzymatic process involved in glutamate metabolism, redistribution of glutamate into tissue, and acute stress response. Regardless of the mechanism involved, decreased blood glutamate concentration is associated with improved neurological outcome. This review focuses on the physiological, mechanistic and clinical roles of blood glutamate scavenging, particularly in the context of acute and chronic CNS injury. We discuss the details of brain-to-blood glutamate efflux, auto-regulation mechanisms of blood glutamate, natural and exogenous blood glutamate scavenging systems, and redistribution of glutamate. We then propose different applied methodologies to reduce blood and brain glutamate concentrations and discuss the neuroprotective role of blood glutamate scavenging.

The effect of blood glutamate scavengers oxaloacetate and pyruvate on neurological outcome in a rat model of subarachnoid hemorrhage.

Blood glutamate scavengers have been shown to effectively reduce blood glutamate concentrations and improve neurological outcome after traumatic brain injury and stroke in rats. This study investigates the efficacy of blood glutamate scavengers oxaloacetate and pyruvate in the treatment of subarachnoid hemorrhage (SAH) in rats. Isotonic saline, 250mg/kg oxaloacetate, or 125mg/kg pyruvate was injected intravenously in 60 rats, 60 minutes after induction of SAH at a rate of 0.1ml/100g/min for 30 minutes. There were 20 additional rats that were used as a sham-operated group. Blood samples were collected at baseline and 90 minutes after SAH. Neurological performance was assessed at 24h after SAH. In half of the rats, glutamate concentrations in the cerebrospinal fluid were measured 24h after SAH. For the remaining half, the blood brain barrier permeability in the frontal and parieto-occipital lobes was measured 48h after SAH. Blood glutamate levels were reduced in rats treated with oxaloacetate or pyruvate at 90 minutes after SAH (p < 0.001). Cerebrospinal fluid glutamate was reduced in rats treated with pyruvate (p < 0.05). Neurological performance was significantly improved in rats treated with oxaloacetate (p < 0.05) or pyruvate (p < 0.01). The breakdown of the blood brain barrier was reduced in the frontal lobe in rats treated with pyruvate (p < 0.05) and in the parieto-occipital lobes in rats treated with either pyruvate (p < 0.01) or oxaloacetate (p < 0.01). This study demonstrates the effectiveness of blood glutamate scavengers oxaloacetate and pyruvate as a therapeutic neuroprotective strategy in a rat model of SAH.

Relationship between glutamate, GOT and GPT levels in maternal and fetal blood: A potential mechanism for fetal neuroprotection

BackgroundExcess glutamate in the brain is thought to be implicated in the pathophysiology of fetal anoxic brain injury, yet little is known about the mechanisms by which glutamate is regulated in the fetal brain. This study examines whether there are differences between maternal and fetal glutamate concentrations, and whether a correlation between them exists. Methods10ml of venous blood was extracted from 87 full-term (>37weeks gestation) pregnant women in active labor. Immediately after delivery of the neonate, 10ml of blood from the umbilical artery and vein was extracted. Samples were analyzed for levels of glutamate, glutamate‐oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT). ResultsFetal blood glutamate concentrations in both the umbilical artery and vein were found to be significantly higher than maternal blood (p<0.001). Similarly, fetal serum GOT levels in the umbilical artery and vein were found to be significantly higher than maternal GOT levels (p<0.001). The difference in GPT levels between maternal and fetal serum was not statistically significant. There was no difference in fetal glutamate, GOT or GPT between the umbilical artery and vein. There was an association observed between glutamate levels in maternal blood and glutamate levels in both venous (R=0.32, p<0.01) and arterial (R=0.33, p<0.05) fetal blood. ConclusionsThis study demonstrated that higher baseline concentrations of blood glutamate are present in fetal blood compared with maternal blood, and this was associated with elevated GOT, but not GPT levels. An association was observed between maternal and fetal blood glutamate levels.