Blood Glutamate Levels Research Articles

Diet's Impact on Post-Traumatic Brain Injury Depression: Exploring Neurodegeneration, Chronic Blood-Brain Barrier Destruction, and Glutamate Neurotoxicity Mechanisms.

Traumatic brain injury (TBI) has a profound impact on cognitive and mental functioning, leading to lifelong impairment and significantly diminishing the quality of life for affected individuals. A healthy blood-brain barrier (BBB) plays a crucial role in guarding the brain against elevated levels of blood glutamate, making its permeability a vital aspect of glutamate regulation within the brain. Studies have shown the efficacy of reducing excess glutamate in the brain as a treatment for post-TBI depression, anxiety, and aggression. The purpose of this article is to evaluate the involvement of dietary glutamate in the development of depression after TBI. We performed a literature search to examine the effects of diets abundant in glutamate, which are common in Asian populations, when compared to diets low in glutamate, which are prevalent in Europe and America. We specifically explored these effects in the context of chronic BBB damage after TBI, which may initiate neurodegeneration and subsequently have an impact on depression through the mechanism of chronic glutamate neurotoxicity. A glutamate-rich diet leads to increased blood glutamate levels when contrasted with a glutamate-poor diet. Within the context of chronic BBB disruption, elevated blood glutamate levels translate to heightened brain glutamate concentrations, thereby intensifying neurodegeneration due to glutamate neurotoxicity.

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.

Blood glutamate scavenging as a novel glutamate-based therapeutic approach for post-traumatic brain injury anxiety and social impairment

Traumatic brain injury (TBI) is a serious condition that is associated with an increased risk of severe, long-term psychiatric consequences. Drugs that target the glutamatergic system have proven successful in treating both TBI and many of its psychiatric sequelae. Blood glutamate scavengers (BGS) cause a decrease in blood glutamate levels, leading to a reduction in glutamate’s concentration gradient from the brain to the blood and decreased levels of brain glutamate. This study evaluated the BGS pyruvate as a treatment for TBI-related neuropsychiatric conditions in a rat model. 213 rats were divided into four groups in a 2 × 2 design: Sham or TBI rats treated with pyruvate or control treatment. Magnetic resonance imaging, neurological status, brain glutamate and blood glutamate levels were assessed following the injury. Four weeks after the start of treatment, all rats underwent behavioral tests to assess anxious behavior and social impairment (aggressive and hierarchical behavior). Rats responded positively to pyruvate in several tasks, lowering brain glutamate levels and reducing anxiety and depression, as well as modulating TBI-related changes in social behavior. Glutamate scavenging with pyruvate may be an effective therapeutic option for post-TBI behavioral changes by reducing associated elevations in brain glutamate levels.

Abstract 104: Taurine As Biomarker And Therapeutic Target For Cardiac Arrest

Introduction: Out-of-hospital cardiac arrest (CA) is a leading cause of death with high mortality. Most patients die from post-CA syndrome due to ischemia/reperfusion injury-triggered responses. Taurine and glutamate, amino acids with cellular activities that are expressed primarily in heart and brain tissues, respectively, are released in response to CA. Hypothesis: Taurine and glutamate levels in blood reflect the extent of injury of CA. Taurine and glutamate could potentially regulate CA outcomes. Methods: Adult CA patients (n=51, 19 survivors, S and 32 nonsurvivors, NS; 35 received cooling treatment, C while 16 did not, NC) at an urban academic ED were enrolled from 2018-2019. Plasma taurine and glutamate collected at various time points including hospital arrival, 6, 24, 48 and 72 hours after arrival, and measured with commercially available assay kits. In a mouse model, 8-min asystolic cardiac arrest was induced with KCl, followed by initiation of CPR and randomized to blinded administration of taurine (50 mg/kg) or saline placebo at 90 second during CPR. Survival (4h) and mean arterial blood pressure (MAP) were evaluated. The Wilcoxon test and generalized estimating equation were used for comparison at each time point and longitudinal trend analysis for human data. Kaplan-Meier estimate and T-test were used for survival and mean comparison in mice. p <0.05 was considered statistically significant. Results: Plasma taurine and glutamate levels were highest at R0 and decreased over time in both S and NS, and were higher in NS than S. Taurine levels were significantly associated with survival (NS 66.24±41.36 vs. S 37.48±19.46 at 6h, p <0.05) while glutamate levels were not. Taurine levels in both C and NC groups demonstrated a significantly decreasing trend over time, but the C group showed more reduction ( p <0.05), while glutamate levels showed no significant trend. In mice, compared to saline, taurine treatment markedly improved 4h survival and MAP post-ROSC. Conclusions: Decreased release of taurine into blood is correlated with CA survival and may regulate CA outcomes. It has high translational potential as a biomarker for predicting CA survival, guiding cooling treatment, and serving as a therapeutic target to improve CA outcomes.

Genetically predicted circulating levels of glycine, glutamate, and serotonin in relation to the risks of three major neurodegenerative diseases: A Mendelian randomization analysis.

It has been previously postulated that blood neurotransmitters might affect risks of neurodegenerative diseases. Here, a Mendelian Randomization (MR) study was conducted to explore whether genetically predicted concentrations of glycine, glutamate and serotonin were associated with risks of Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). From three genome-wide association studies of European ancestry, single nucleotide polymorphisms strongly associated with glycine, glutamate and serotonin were selected as genetic instrumental variables. Corresponding summary statistics were also obtained from the latest genome-wide association meta-analyses of AD, PD and ALS. The inverse-variance weighted MR and multiple sensitivity analyses were performed to evaluate causal effects of genetically predicted levels of neurotransmitters on risks of neurodegenerative diseases. The statistical significance threshold was set at P < 0.0056 using the Bonferroni-correction, while 0.0056 < P < 0.05 was considered suggestive evidence for a causal association. There was a causal association of elevated blood glutamate levels with higher AD risks. The odds ratio (OR) of AD was 1.311 [95% confidence interval (CI), 1.087–1.580; P = 0.004] per one standard deviation increase in genetically predicted glutamate concentrations. There was suggestive evidence in support of a protective effect of blood serotonin on AD (OR = 0.607; 95% CI, 0.396–0.932; P = 0.022). Genetically predicted glycine levels were not associated with the risk of AD (OR = 1.145; 95% CI, 0.939–1.396; P = 0.180). Besides, MR analyses indicated no causal roles of three blood neurotransmitters in PD or ALS. In conclusion, the MR study provided evidence supporting the association of elevated blood glutamate levels with higher AD risks and the association of increased blood serotonin levels with lower AD risks. Triangulating evidence across further study designs is still warranted to elucidate the role of blood neurotransmitters in risks of neurodegenerative diseases.

Comparison of blood tryptophan and glutamate levels in children and adolescents with autism and healthy controls

Studies show that there are significant increments of glutamate levels in individuals with autism spectrum disorders, which suggests that this amino acid could be a potential biomarker. We aimed to evaluate the concentration tryptophan and glutamate in the blood plasma of children with autism and their correlation with symptoms severity in children and adolescents diagnosed with autism. We assessed the plasma tryptophan and glutamate levels in the 35 children with autism and 31 unrelated healthy controls. The plasma amino acid analysis was performed by a high-pressure liquid chromatograph (HPLC). The Gilliam Autism Rating Scale (GARS-2) was used to evaluate autism severity. Compared with the control group, the autism group had higher levels of plasma glutamate (p = .005), and there was a negative correlation between stereotyped patterns score, total score of GARS-2, and plasma tryptophan levels in the autism group (p = .012, r = -0.42 and p = .034, r = -0.36 respectively). There was also a positive correlation between stereotyped patterns score and plasma glutamate levels in ASD boys (p = .050, r = 0.39). Our findings provide evidence of elevated plasma glutamate levels and for correlations between tryptophan, glutamate and severity of symptoms in children with autism.

Blood Glutamate Scavenging With Pyruvate as a Novel Preventative and Therapeutic Approach for Depressive-Like Behavior Following Traumatic Brain Injury in a Rat Model.

Depression is a common and serious complication following traumatic brain injury (TBI). Both depression and TBI have independently been associated with pathologically elevated extracellular brain glutamate levels. In the setting of TBI, blood glutamate scavenging with pyruvate has been widely shown as an effective method to provide neuroprotection by reducing blood glutamate and subsequent brain glutamate levels. Here we evaluate pyruvate as a novel approach in the treatment and prevention of post-TBI depression-like behavior in a rat model. Rats were divided into five groups: (1) sham-operated control with pyruvate, (2) sham-operated control with placebo, (3) post-TBI with placebo, (4) post-TBI given preventative pyruvate, and (5) post-TBI treated with pyruvate. These groups had an equal number of females and males. Rats were assessed for depressive-like behavior, neurological status, and glutamate levels in the blood and brain. Post-TBI neurological deficits with concurrent elevations in glutamate levels were demonstrated, with peak glutamate levels 24 h after TBI. Following TBI, the administration of either prophylactic or therapeutic pyruvate led to reduced glutamate levels, improved neurologic recovery, and improved depressive-like behavior. Glutamate scavenging with pyruvate may be an effective prophylactic and therapeutic option for post-TBI depression by reducing associated elevations in brain glutamate levels.

The Effects of Glucagon and Insulin Combination toward on Neurodegeneration Following Traumatic Brain Injury in Rat Model

BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability in the productive age. Glutamate excitotoxicity and hyperglycemia those occur following TBI are among the factors those influence secondary brain injury. AIM: This study aimed to determine the effect of glucagon and insulin combination on neuronal necrosis following TBI. METHODS: A total of 28 male wistar rats were randomized into four experimental groups: placebo, insulin, glucagon, and combination of glucagon and insulin. Each animal underwent controlled cortical impact model of TBI. The blood glucose and glutamate levels were measured before and 4 h following TBI. The brain tissues were collected to evaluate neuronal necrosis. RESULTS: Glucagon or glucagon and insulin combination were able to prevent the increased of blood glutamate levels following TBI (p &lt; 0.05). Glucagon administration was associated high blood glucose level (198.10 ± 32.58 mg/dL); a combination with insulin was able to minimize the increased of blood glucose level (166.53 ± 18.48 mg/dL). Combination of glucagon and insulin had a lower number of neuronal necrosis compare to the other groups (p &lt; 0.005). CONCLUSION: The combination of glucagon and insulin potentially exhibit neuroprotection effect on rats following TBI as being demonstrated by lower number of neuronal necrosis. This finding further indicates the role of glucose homeostasis in neuroprotection.

Alteration of blood inflammation and glutamate level in parietal precuneus cortex within patients with recent history of suicide attempt: A study of magnetic resonance spectroscopy

Suicidal behavior (SB) has been associated with structural and functional impairments in neuroimaging studies and with an increase of peripheral inflammation. We assumed that the increased level of peripheral inflammation markers could be correlated with some abnormalities of brain metabolites in areas involved in suicidal vulnerability such as the anterior and posterior cingulate gyrus cortex (ACC and PCC), the orbito-frontal cortex (OFC) and parietal precuneus cortex (PPC). This hypothesis has been tested by studying the association between levels of 6 cerebral metabolites [i.e. Glutamate (Glu), glutamine (Gln), N-Acetyl aspartate (TNAA), Myo-inositol (Myo)…], 15 biomarkers of inflammation (i.e. C reactive protein (CRP), interleukin (IL) 2, IL1β, IL6, RANTES…) and 8 clinical variables known to be involved in suicidal vulnerability (i.e. depression, childhood trauma, impulsivity, suicidal ideation…). Sixty-six participants were recruited and divided into three groups: 21 depressed patients with a recent SA ( Fig. 1 ). A blood sample was collected to measure peripheral inflammation. We found a higher level of C reactive protein (CRP) in suicide attempters than in both affective controls and healthy controls. CRP level was negatively correlated with concentrations of Glutamate (R = −0.30 P 40% P

The effect of pyruvate on the development and progression of post-stroke depression: A new therapeutic approach

Post-stroke depression (PSD) is a common and serious complication following stroke. Both stroke and depression have independently been associated with pathologically elevated glutamate levels in the brain's extra-cerebral fluid (ECF). Here we evaluate an alternative therapeutic approach to PSD with pyruvate. Rats were randomly assigned into one of 3 groups: Middle Cerebral Artery Occlusion (MCAO) plus pyruvate treatment, MCAO plus placebo treatment, and sham operated rats. Post-MCAO depressive and anxiety-like behavior was assessed, along with neurological status, brain infarct zone, brain edema, blood brain barrier (BBB) breakdown, cerebrospinal fluid and blood glutamate levels. Anxiety-like behavior and levels of blood alanine and α-ketoglutarate were measured in naïve rats treated with pyruvate, as a control. Post-stroke neurological deficit with concurrent elevation in glutamate levels were demonstrated, with peak glutamate levels 24 h after MCAO. Treatment with pyruvate led to reduced glutamate levels 24 h after MCAO and improved neurologic recovery. Pyruvate treatment reduced lesion volume, brain edema and the extent of BBB permeability 24 h post-MCAO. Naïve rats treated with pyruvate showed increased levels of α-ketoglutarate. Rats demonstrated post-stroke depressive behavior that was improved by the administration of pyruvate. There was less anxiety-like behavior in post-stroke rats treated with placebo in comparison to the post-stroke rats treated with pyruvate or sham operated rats. Glutamate scavenging with pyruvate appears to be an effective as a method in providing neuroprotection following stroke and as a therapeutic option for the treatment of PSD by reducing the consequent elevations in CNS glutamate levels.

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.

Glutamine and Glutamate Supplementation Increases the Levels of These Amino Acids in the Milk of Pasture-fed Mares

Background: L-Glutamine (Gln), the most abundant free alpha amino acid in the body, plays a major role in the transport of nitrogen and carbon between tissues, and is an important source of respiratory energy for intestinal and immune system cells. Mares lose lean body mass during lactation, when plasma and milk Gln levels change significantly. However, supplementation with Gln combined with other amino acids may not alter equine plasma Gln levels. The work reported here was designed to test the hypothesis that supplementation with a mixture of glutamine and glutamate (AminoGut) alters blood and milk free glutamine and glutamate levels in pasture-fed lactating mares.Materials, Methods &amp; Results: This study involved 31 multiparous Quarter Horse mares, which were divided into three groups immediately postpartum, as follows: G-CON (n = 19); G-50 g supplemented with 50 g of Gln + Glu plus 200 g of concentrate (n = 6); and G-100 g, supplemented with 100 g of Gln + Glu plus 200 g of concentrate (n = 6). Blood and milk samples were collected on the day of parturition prior to supplementation, and monthly until weaning. The milk samples were used to analyze the Gln, Glu composition and levels, while the blood samples were used for further analysis of blood biomarkers. The results were analyzed by ANOVA and by Tukey’s test and the P value was set at 5%. The G-CON group showed a significant reduction of 11-35% in the mean blood glutamine levels from the first month postpartum and throughout lactation. In contrast, blood glutamine levels in groups G-50 g and G-100 g did not change significantly from parturition through 5 months of lactation. The supplemented groups showed no significant differences in blood variables such as protein, albumin, urea, creatinine, cholesterol, triglycerides and minerals. Free glutamine levels in milk did not change from parturition through the end of lactation in the G-CON group, but groups G-50 g and the G-100 g showed a marked rise in milk glutamine levels throughout the first three months of lactation (~3x), which remained high (~2x) until the foals were weaned (P &gt; 0.05).Discussion: The results of this study indicate that Gln + Glu supplementation successfully increased Gln levels in mare milk in the first three months of lactation, and Glu levels in G-100 g in the first four months, without affecting the levels of these amino acids in the animals’ blood, which remained similar to data obtained at parturition. In fact, the Gln levels in both supplemented groups exceeded 1,000 mmol/mL throughout lactation, unlike those of the control group and of the samples obtained at parturition. Moreover, supplementation did not produce significant changes in blood biomarkers, including those pertaining to protein metabolism (urea, creatinine, uric acid, albumin and total proteins), indicating that the product used for supplementation did not interfere in these biomarkers, which remained within the normal physiological variations for the species. It was concluded that daily dietary supplementation with 50 g of a mixture of glutamine and glutamate produced an effect similar to supplementation with 100 g/day. Both supplementation protocols succeeded in raising glutamine levels in mare milk in the first three months of lactation, without interfering in blood biomarkers or milk composition. In view of the cost of the product, we recommend that the daily diet of mares during lactation be supplemented with 50 g of a mixture of Gln + Glu in order to produce the desired nutritional effects.

Elevated peripheral blood glutamate levels in major depressive disorder.

PurposeThere is growing evidence that glutamatergic signaling may be involved in major depressive disorder (MDD). In regard to peripheral blood glutamate changes in MDD, inconsistent findings have been reported. The purpose of the present study was to evaluate whether blood glutamate levels differed between MDD patients and control participants.Materials and methodsWe conducted a systematic review and meta-analysis of 12 association studies between blood glutamate levels and MDD in a total of 529 MDD patients and 590 controls. Subsequently, we conducted subgroup analyses and a meta-regression analysis to examine the sources of potential heterogeneity.ResultsA random effects model showed that blood glutamate levels were significantly higher in MDD patients than in controls (standardized mean difference=0.54, 95% CI=0.27–0.82, p=8.5×10−5) with high heterogeneity (I2=75.0%, p<0.05). Subgroup analyses showed elevated glutamate levels in MDD patients compared with controls in plasma, but not serum studies, and in studies using high-performance liquid chromatography but not with mass spectrometry for glutamate assay. A meta-regression analysis showed no effects of age, gender, medication use, sample size, and published year on blood glutamate levels.ConclusionOur findings suggest that altered glutamate levels may be implicated in MDD, which provides further evidence of glutamatergic dysfunction in MDD.

Blood Glutamate Levels Are Closely Related to Acute Lung Injury and Prognosis after Stroke.

Acute lung injury (ALI) is a serious complication of stroke that occurs with a high incidence. Our preclinical results indicated that ALI might be related to blood glutamate levels after brain injury. The purpose of this study was to assess dynamic changes in blood glutamate levels in patients with stroke and to determine the correlation between blood glutamate levels, ALI, and long-term prognosis after stroke. Venous blood samples were collected from controls and patients with stroke at admission and on the third and seventh day after the onset of stroke. Patients were followed for 3 months. The correlations among blood glutamate levels, severities of stroke and ALI, and long-term outcomes were analyzed, and the predictive values of blood glutamate levels and severity scores for ALI were assessed. In this study, a total of 384 patients with stroke were enrolled, with a median age of 59 years. Patients showed significantly increased blood glutamate levels within 7 days of stroke onset (p < 0.05), and patients with more severe injuries showed higher blood glutamate levels. Moreover, blood glutamate levels were closely related to the occurrence (adjusted odds ratio, 3.022, p = 0.003) and severity (p < 0.001) of ALI and the long-term prognosis after stroke (p < 0.05), and they were a more accurate predictor of ALI than the more commonly used severity scores (p < 0.01). These results indicated that an increased blood glutamate level was closely related to the development of ALI and a poor prognosis after stroke. http://www.chictr.org.cn, identifier ChiCTR-RPC-15006770.

Blood Glutamate Reducing Effect of Hemofiltration in Critically Ill Patients.

Glutamate toxicity plays a well-established role in secondary brain damage following acute and chronic brain insults. Previous studies have demonstrated the efficacy of hemodialysis and peritoneal dialysis in reducing blood glutamate levels. However, these methods are not viable options for hemodynamically unstable patients. Given more favorable hemodynamics, longer treatment, and less needed anticoagulation, we investigated whether hemofiltration could be effective in lowering blood glutamate levels. Blood samples were taken from 10 critically ill patients immediately before initiation of hemofiltration and after 1, 2, 4, 6, and 12h, for a total of 6 blood samples. Samples were sent for determination of glutamate, glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), hemoglobin, hematocrit, urea, creatinine, glucose, sodium, potassium, platelet, and white blood cell (WBC) levels. There was a statistically significant reduction in blood glutamate levels at all time points compared to baseline levels. There was no difference in levels of GOT or GPT. Hemofiltration can be a promising method of reducing blood glutamate levels, especially in critically ill patients where hemodialysis and peritoneal dialysis may be contraindicated.

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.

Blood Glutamate Levels in Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.

ObjectiveGlutamate plays an important role in brain development, neuronal migration, differentiation, survival and synaptogenesis. Recent studies have explored the relationship between blood glutamate levels and autism spectrum disorder (ASD). However, the findings are inconsistent. We undertook the first systematic review with a meta-analysis of studies examining blood glutamate levels in ASD compared with controls.MethodsA literature search was conducted using PubMed, Embase, and the Cochrane Library for studies published before March 2016. A random-effects model was used to calculate the pooled standardized mean difference (SMD) of the outcomes. Subgroup analyses were used to explore the potential sources of heterogeneity, and the publication bias was estimated using Egger’s tests.ResultsTwelve studies involving 880 participants and 446 incident cases were included in this meta-analysis. The meta-analysis provided evidence for higher blood glutamate levels in ASD [SMD = 0.99, 95% confidence interval (95% CI) = 0.58–1.40; P < 0.001] with high heterogeneity (I2 = 86%, P < 0.001) across studies. The subgroup analyses revealed higher glutamate levels in ASD compared with controls in plasma [SMD = 1.04, 95% CI = 0.58–1.50; P < 0.001] but not true in serum [SMD = 0.79, 95% CI = -0.41–1.99; P = 0.20]. Studies employing high performance liquid chromatography (HPLC) or liquid chromatography-tandem mass spectrometry (LC-MS) assays also revealed higher blood glutamate levels in ASD. A sensitivity analysis found that the results were stable, and there was no evidence of publication bias.ConclusionsBlood glutamate levels might be a potential biomarker of ASD.

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.

Blood glutamate grabbing does not reduce the hematoma in an intracerebral hemorrhage model but it is a safe excitotoxic treatment modality.

Recent studies have shown that blood glutamate grabbing is an effective strategy to reduce the excitotoxic effect of extracellular glutamate released during ischemic brain injury. The purpose of the study was to investigate the effect of two of the most efficient blood glutamate grabbers (oxaloacetate and recombinant glutamate oxaloacetate transaminase 1: rGOT1) in a rat model of intracerebral hemorrhage (ICH). Intracerebral hemorrhage was produced by injecting collagenase into the basal ganglia. Three treatment groups were developed: a control group treated with saline, a group treated with oxaloacetate, and a final group treated with human rGOT1. Treatments were given 1 hour after hemorrhage. Hematoma volume (analyzed by magnetic resonance imaging (MRI)), neurologic deficit, and blood glutamate and GOT levels were quantified over a period of 14 days after surgery. The results observed showed that the treatments used induced a significant reduction of blood glutamate levels; however, they did not reduce the hematoma, nor did they improve the neurologic deficit. In the present experimental study, we have shown that this novel therapeutic strategy is not effective in case of ICH pathology. More importantly, these findings suggest that blood glutamate grabbers are a safe treatment modality that can be given in cases of suspected ischemic stroke without previous neuroimaging.