Blood Glutamate Levels Research Articles

MRS of brain metabolite levels demonstrates the ability of scavenging of excess brain glutamate to protect against nerve agent induced seizures.

This study describes the use of in vivo magnetic resonance spectrocopy (MRS) to monitor brain glutamate and lactate levels in a paraoxon (PO) intoxication model. Our results show that the administration of recombinant glutamate-oxaloacetate transaminase (rGOT) in combination with oxaloacetate (OxAc) significantly reduces the brain-accumulated levels of glutamate. Previously we have shown that the treatment causes a rapid decrease of blood glutamate levels and creates a gradient between the brain and blood glutamate levels which leads to the efflux of excess brain glutamate into the blood stream thereby reducing its potential to cause neurological damage. The fact that this treatment significantly decreased the brain glutamate and lactate levels following PO intoxication suggests that it could become a new effective neuroprotective agent.

Effect of Short-term 900 MHz low level electromagnetic radiation exposure on blood serotonin and glutamate levels.

Long term exposure to low level electromagnetic radiation (LLER) by using cellular phones causes serious health problems. Ten male Wistar Albino rats were anesthetized 30 min before the LLER exposure, 0.5 ml blood was taken from the tail vein of rats in order to determine control values. Rats were grouped by three and placed on a plexi-glass flat. A fixed equivalent frequency emitter device was used. A sign to be an electromagnetic field 15.14 V/m (608 mW/m(2)) in strength in the head region with 100 kHz FM modulation at 900 MHz was applied to the animals. After calculating the ideal position for the device, electromagnetic LLER energy was applied for 45 minutes from a distance to be equal with energy transmitted by a mobile phone from a 0.5-1 cm distance to their head regions. After 1.5 hours and before the rats awoke, 0.5 ml of blood was taken from the tail veins in order to determine the treatment values. Plasma 5-HT and glutamate levels were measured by enzyme immunoassay (EIA) using commercial kits. It was found that a single 45 min of LLER exposure increased the blood 5-HT level significantly, but did not change the glutamate level of rats. It was concluded that even a single 45 min of LLER exposure may produce an increase in 5-HT level without changing the blood glutamate level. Increased 5-HT level may lead to a retarded learning and a deficit in spatial memory (Tab. 2, Fig. 2, Ref. 24).

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.

The effects of peritoneal dialysis on blood glutamate levels: Implementation for Neuroprotection

The effects of peritoneal dialysis on blood glutamate levels: Implementation for Neuroprotection

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

Influence of prenatal exposure to environmental pollutants on human cord blood levels of glutamate

Some chemicals released into the environment, including mercury and some organochlorine compounds (OCs), are suspected to have a key role on subclinical brain dysfunction in childhood. Alteration of the glutamatergic system may be one mechanistic pathway. We aimed to determine whether mercury and seven OCs, including PCBs 138, 153, and 180, DDT and DDE, hexachlorobenzene (HCB), and beta-hexachlorocyclohexane (β-HCH) influence the cord levels of two excitatory amino acids, glutamate and aspartate. Second, we evaluated if this association was mediated by glutamate uptake measured in human placental membranes. The study sample included 40 newborns from a Spanish cohort selected according to cord mercury levels. We determined the content of both amino acids in cord blood samples by means of HPLC and assessed their associations with the contaminants using linear regression analyses, and the effect of the contaminants on glutamate uptake by means of [3H]-aspartate binding in human placenta samples. PCB138, β-HCH, and the sum of the three PCBs and seven OCs showed a significant negative association with glutamate levels (decrease of 51, 24, 56 and 54%, respectively, in glutamate levels for each 10-fold increase in the contaminant concentration). Mercury did not show a significant correlation neither with glutamate nor aspartate levels in cord blood, however a compensatory effect between T-Hg and both PCB138, and 4,4′-DDE was observed. The organo-metallic derivative methylmercury completely inhibited glutamate uptake in placenta while PCB138 and β-HCH partially inhibited it (IC50 values: 4.9±0.8μM, 14.2±1.2nM and 6.9±2.9nM, respectively). We conclude that some environmental toxicants may alter the glutamate content in the umbilical cord blood, which might underlie alterations in human development.

Scavenging of blood glutamate for enhancing brain-to-blood glutamate efflux

The presence of excess glutamate in the brain interstitial fluid characterizes several acute pathological conditions of the brain, including traumatic brain injury and stroke. It has been demonstrated that it is possible to eliminate excess glutamate in the brain by decreasing blood glutamate levels and, accordingly, accelerating the brain-to-blood glutamate efflux. It is feasible to accomplish this process by activating blood resident enzymes in the presence of the respective glutamate cosubstrates. In the present study, several glutamate cosubstrates and cofactors were studied in an attempt to identify the optimal conditions to reduce blood glutamate levels. The administration of a mixture of 1mM pyruvate and oxaloacetate (Pyr/Oxa) for 1h decreased blood glutamate levels by ≤50%. The addition of lipoamide to this mixture resulted in a further reduction in blood glutamate levels of >80%. In addition, invivo experiments showed that lipoamide together with Pyr/Oxa is able to decrease blood glutamate levels to a greater extent than Pyr/Oxa alone, and accordingly, this enhances the glutamate efflux from the brain to the blood. These results may outline a novel neuroprotective strategy with increased effectiveness for the removal of excess brain glutamate in various neurodegenerative conditions.

S.24.01 Rare mutations in N-methyl-D-aspartate glutamate receptors in schizophrenia and autism spectrum disorders

Despite of the great efforts that move forward to clarify the pathophysiologic mechanisms in autism, the cause of this disorder, however, remains largely unknown. There is an increasing body of literature concerning neurochemical contributions to the pathophysiology of autism. We aimed to determine blood and brain levels of glutamate in children with autistic disorder and to correlate between them. The study included 10 children with autism and 10 age- and sex-matched healthy controls. Blood glutamate levels were measured using high performance liquid chromatography technique. Brain glutamate levels were measured using proton magnetic resonance spectroscopy. The mean blood and brain glutamate levels were significantly higher in patients than controls (p < 0.001). There was highly significant positive correlation between blood glutamate level and brain glutamate levels in the four tested brain regions (p < 0.001). Glutamate plays an important role in the pathogenesis of autism. Further larger studies are required to support our findings.

Amelioration of ischemic brain damage by peritoneal dialysis

Ischemic stroke is a devastating condition, for which there is still no effective therapy. Acute ischemic stroke is associated with high concentrations of glutamate in the blood and interstitial brain fluid. The inability of the tissue to retain glutamate within the cells of the brain ultimately provokes neuronal death. Increased concentrations of interstitial glutamate exert further excitotoxic effects on healthy tissue surrounding the infarct zone. We developed a strategy based on peritoneal dialysis to reduce blood glutamate levels, thereby accelerating brain-to-blood glutamate clearance. In a rat model of stroke, this simple procedure reduced the transient increase in glutamate, consequently decreasing the size of the infarct area. Functional magnetic resonance imaging demonstrated that the rescued brain tissue remained functional. Moreover, in patients with kidney failure, peritoneal dialysis significantly decreased glutamate concentrations. Our results suggest that peritoneal dialysis may represent a simple and effective intervention for human stroke patients.

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.

Glutamate oxaloacetate transaminase: A new key in the dysregulation of glutamate in migraine patients

Based on the capacity of the blood-resident enzyme glutamate oxaloacetate transaminase (GOT) to metabolize blood glutamate, our aim was to study the association of GOT activity with serum glutamate levels and clinical parameters in patients with migraine. This case-control study included 45 episodic migraine patients (IHS 2004 criteria) and 16 control subjects. We analyzed glutamate and GOT activity in peripheral blood samples obtained during interictal periods and migraine attacks ( N = 15). Frequency, severity, and duration of attacks and time of evolution were also recorded. Migraine patients showed lower GOT activity than controls (15.2 ± 2.9 vs. 18.7 ± 3.8 U/l) and higher levels of glutamate (153.7 ± 68.6 vs. 121.5 ± 59.2 μM) (all P < 0.05). A negative correlation was found between GOT activity and glutamate levels ( R = -0.493; P < 0.0001) in interictal periods; however, this negative correlation was lost during attacks ( R = -0.026; P = 0.925). During attacks, we found a positive correlation between the time elapsed from attack onset and glutamate levels ( R = 0.738; P < 0.0001), but not for GOT activity ( R = -0.075; P = 0.809). Migraine patients showed reduced GOT activity and increased levels of blood glutamate levels as compared to control subjects. Furthermore, a negative correlation was found between GOT activity and glutamate levels in interictal periods.

The Role of Hypothermia in the Regulation of Blood Glutamate Levels in Naive Rats

The exact mechanism of hypothermia-induced neuroprotection has not been determined yet; however, we hypothesized that it may be mediated by a blood glutamate-scavenging effect. Here, we examine the effect of hypothermic conditions (mild, moderate, and deep) on blood glutamate levels in naive rats. To identify the mechanism of hypothermia-induced glutamate reduction, we also measured concentrations of glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT), the primary regulators of glutamate concentration in blood. Rats were anesthetized with isoflurane, and their rectal temperature was maintained for 6 hours at 36 to 37°C, 33 to 36°C, 30 to 32°C, 18 to 22°C, or was not maintained artificially. At 6 hours, active cooling was discontinued and rats were allowed to rewarm. There were 12 rats in each group for a total of 60 rats. Blood samples were drawn at 0, 3, 6, 12, 24, and 48 hours for the determination of blood glutamate, GOT, and GPT levels. A strong correlation between body temperature and blood glutamate levels was observed (P<0.001). Mild (33 to 36°C) and moderate (30 to 32°C) hypothermia led to reduced blood glutamate levels (P<0.001). Deep hypothermia (18 to 22°C) was associated with significant elevations in blood glutamate levels (P<0.001). Hypothermia, irrespective of the degree, led to elevations in GOT in plasma (P<0.001). Mild and moderate hypothermia led to a reduction in blood glutamate levels in rats, whereas deep hypothermia was associated with a significant elevation in blood glutamate levels. We further demonstrated an elevation of GOT and GPT levels, supporting their involvement in reducing blood glutamate by the conversion of glutamate to 2-ketoglutarate. We suggest that the neuroprotective properties of hypothermia may be partially because of a blood glutamate-scavenging mechanism.

Blood and brain glutamate levels in children with autistic disorder

Despite of the great efforts that move forward to clarify the pathophysiologic mechanisms in autism, the cause of this disorder, however, remains largely unknown. There is an increasing body of literature concerning neurochemical contributions to the pathophysiology of autism. We aimed to determine blood and brain levels of glutamate in children with autistic disorder and to correlate between them. The study included 10 children with autism and 10 age- and sex-matched healthy controls. Blood glutamate levels were measured using high performance liquid chromatography technique. Brain glutamate levels were measured using proton magnetic resonance spectroscopy. The mean blood and brain glutamate levels were significantly higher in patients than controls (p<0.001). There was highly significant positive correlation between blood glutamate level and brain glutamate levels in the four tested brain regions (p<0.001). Glutamate plays an important role in the pathogenesis of autism. Further larger studies are required to support our findings.

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.

The effects of hemodialysis on blood glutamate levels in chronic renal failure: Implementation for neuroprotection

PurposeThe purpose of the present study is to investigate whether hemodialysis (HD) is effective in lowering blood glutamate levels. In addition, we examined the effect of HD on glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) levels in the blood and described the rate and pattern of blood glutamate clearance during HD. Materials and MethodsBlood samples were taken from 45 patients with stage V chronic kidney disease immediately after initiation of HD and hourly, for a total of 5 blood samples. Samples were sent for determination of glutamate, glucose, GOT, GPT, hemoglobin, hematocrit, urea, and creatinine levels. A blood sample from 25 healthy volunteers without chronic renal failure was used as a control for the determination of baseline blood levels of glutamate, GOT, and GPT. ResultsGlutamate and GPT levels in patients on HD were higher at baseline compared with healthy controls (P < .001). In the first 3 hours after HD, there was a decrease in blood glutamate levels compared with baseline levels (P < .00001). At the fourth hour, there was an increase in blood glutamate levels compared with the third hour (P < .05). ConclusionsHemodialysis may be a promising method of reducing blood glutamate levels.

Pharmacokinetics of Glutamate–Oxaloacetate Transaminase and Glutamate–Pyruvate Transaminase and Their Blood Glutamate-Lowering Activity in Naïve Rats

Traumatic brain injury (TBI) and stroke lead to elevated levels of glutamate in the brain that negatively affect the neurological outcomes in both animals and humans. Intravenous administration of glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) enzymes can be used to lower the blood glutamate levels and to improve the neurological outcome following TBI and stroke. The objective of this study was to analyze the pharmacokinetics and to determine the glutamate-lowering effects of GOT and GPT enzymes in naïve rats. We determined the time course of serum GOT, GPT, and glutamate levels following a single intravenous administration of two different doses of each one of the studied enzymes. Forty-six male rats were randomly assigned into one of 5 treatment groups: saline (control), human GOT at dose 0.03 and 0.06 mg/kg and porcine GPT at dose 0.6 and 1.2 mg/kg. Blood samples were collected at baseline, 5 min, and 2, 4, 8, 12, and 24 h after the drug injection and GOT, GPT and glutamate levels were determined. The pharmacokinetics of both GOT and GPT followed one-compartment model, and both enzymes exhibited substantial glutamate-lowering effects following intravenous administration. Analysis of the pharmacokinetic data indicated that both enzymes were distributed predominantly in the blood (central circulation) and did not permeate to the peripheral organs and tissues. Several-hour delay was present between the time course of the enzyme levels and the glutamate-lowering effects (leading to clock-wise hysteresis on concentration-effect curves), apparently due to the time that is required to affect the pool of serum glutamate. We conclude that the interaction between the systemically-administered enzymes (GOT and GPT) and the glutamate takes place in the central circulation. Thus, glutamate-lowering effects of GOT and GPT apparently lead to redistribution of the excess glutamate from the brain's extracellular fluid into the blood and can reduce secondary brain injury due to glutamate neurotoxicity. The outcomes of this study regarding the pharmacokinetic and pharmacodynamic properties of the GOT and GPT enzymes will be subsequently verified in clinical studies that can lead to design of effective neuroprotective treatment strategies in patients with traumatic brain diseases and stroke.

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.

β2 Adrenergic-mediated Reduction of Blood Glutamate Levels and Improved Neurological Outcome After Traumatic Brain Injury in Rats

Isoflurane-anesthetized rats subjected to traumatic brain injury (TBI) show a transient reduction in blood L-glutamate levels. Having previously observed that isoproterenol produces a sustained decrease in blood glutamate levels in naive rats, we investigated the possible effects of nonselective and selective β1 and β2 adrenergic agonists and antagonists both on blood glutamate levels and on the neurological outcomes of rats subjected to TBI. Rats received either 10 mL/kg of isotonic saline 1 hour after TBI, 50 µg/kg of isoproterenol pretreatment 30 minutes before TBI, 10 mg/kg of propranolol pretreatment 60 minutes before TBI, 10 mg/kg of metoprolol pretreatment 60 minutes before TBI, or 10 mg/kg of butaxamine pretreatment 40 minutes before TBI and 10 minutes before pretreatment with 50 µg/kg isoproterenol or 10 mg/kg of propranolol 60 minutes after TBI. A neurological severity score (NSS) was measured at 1, 24, and 48 hours after TBI. Blood glutamate, blood glucose, mean arterial blood pressure, and heart rate were measured at the time of drug injection, at the time of TBI, 60 minutes after TBI, and 90 minutes after TBI. Blood glutamate levels decreased spontaneously by 60 minutes after TBI in the control group (P<0.05), reverting to baseline levels by 90 minutes after TBI. A pretreatment with either 10 mg/kg of metoprolol 60 minutes before TBI or with 50 µg/kg of isoproterenol 30 minutes before TBI also reduced blood glutamate levels (P<0.05) both at 90 minutes after TBI and improved the NSS measured 24 and 48 hours after TBI in comparison with the control saline-treated group. However, a 10-mg/kg butoxamine pretreatment 40 minutes before TBI and 10 minutes before pretreatment with 50 µg/kg of isoproterenol or 10 mg/kg of propranolol 60 minutes before TBI neither affected blood glutamate levels across time after TBI nor caused any significant change in the NSS measured 24 and 48 hours after TBI in comparison with the control saline-treated group. A strong correlation (r(2)=0.73) was demonstrated between the percent decrease in blood glutamate levels at 90 minutes after TBI and the percent improvement of NSS measured 24 hours after TBI. The results suggest that the transient blood glutamate reduction seen after TBI is the result of a stress response and of the activation of the sympathetic nervous system through the β2 adrenergic receptors, causing an increase of the brain-to-blood efflux of glutamate observed with excess brain glutamate levels after a brain insult. This strongly correlates with the neurological improvement observed 24 hours after TBI.