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BACKGROUND 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. METHODS 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. RESULTS Blood glutamate concentrations were significantly reduced by 60 minutes after the infusion of dialysis solution (P

BACKGROUND 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. METHODS 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. RESULTS A strong correlation between body temperature and blood glutamate levels was observed (P

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 (P0.05), 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 (P0.05) 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.

BACKGROUND Elevated levels of glutamate in brain fluids, in the context of several neurodegenerative conditions, are associated with a worsened neurological outcome. Because there is a clear relationship between brain glutamate levels and glutamate levels in the blood, and an association of the latter with stress, the purpose of this study was to investigate the effects of glucose, insulin, and glucagon on rat blood glutamate levels. METHODS Rats received either 1 mL/100 g of rat body weight (BW) intravenous isotonic saline (control), 150 mg/1 mL/100 g BW intravenous glucose, 75 mg/1 mL/100 g BW intravenous glutamate, 50 g/100 g BW intraparitoneal glucagon, or 0.2 UI/100 g BW intraparitoneal insulin. Blood samples were subsequently drawn at 0, 30, 60, 90, and 120 minutes for determination of blood glutamate and glucose levels. RESULTS We observed a significant decrease in blood glutamate levels at 30 minutes after injection of glucose (P

BACKGROUND The animal model of stroke that is most frequently used is a rat model of focal brain ischemia caused by middle cerebral artery occlusion (MCAO). Several studies have reported a link between levels of cell-free DNA (CFD) and neurologic outcome in human stroke. The purpose of this study was to assess brain injury and measure CFD levels in 2 models of MCAO in rats, and to determine whether brain injury correlates with CFD. METHODS A total of 60 rats were used for this study. Twenty rats underwent a sham procedure, 20 rats had MCAO using a monofilament, and 20 rats had MCAO with a silicon-coated filament. Groups were further divided into 2 subgroups. In 1 subgroup of 10 rats, neurologic performance [measured as a neurologic severity score, (NSS)] was measured at 1 and 24 hours after the procedure, and brain edema and infarct volume were determined at 24 hours. In the second subgroup of 10 rats, CFD was measured at 0, 1, 2, 4, 8, 12, and 24 hours and at 2, 3, 4, and 5 days. Neurologic performance (measured as a NSS) was measured at 1 and 24 hours after the procedure. RESULTS The main finding was a significant increase in CFD levels observed 24 hours after the onset of MCAO. The correlation between the total infarct volume and CFD levels of the 3 groups was R=0.78, P

Abnormally high concentrations of glutamate in brain fluids have been shown to be neurotoxic and correlate with a poor neurological outcome following traumatic brain injury (TBI). Since brain fluid glutamate can be reduced by scavenging blood glutamate, the purpose of this study was to investigate factors that may potentially influence levels of blood glutamate, glucose, and the enzymes glutamate-pyruvate transaminase (GPT) and glutamate-oxaloacetate transaminase (GOT) in healthy individuals.Factors that were examined included age, gender, time of last meal or drink, and recent consumption of coffee. A total of 112 healthy volunteers between 18 and 70 years of age participated in the study. The average participant was 38 years old, and the sample consisted of 48 males and 64 females. Five milliliters of venous blood was collected from participants' cubital vein and blood glutamate, glucose, GOT and GPT levels were determined. Participants were then asked to complete a questionnaire addressing their gender, age, time of last meal, time of last drink, and whether coffee was consumed within the last 6 hours.Blood glutamate concentrations were significantly higher in males than in females (P0.001) and may be due to effects of estrogen and progesterone. Concentrations of GOT were significantly higher in males than in females (P0.01). Concentrations of GPT were significantly higher in males than in females (P0.01). There were no other significant differences demonstrated.Understanding the factors that affect blood glutamate levels may give new insight into mechanisms that protect the brain from excess glutamate and result in a better neurological outcome following TBI.

Treatment with oxaloacetate after traumatic brain injury has been shown to decrease blood glutamate levels and protect against the neurotoxic effects of glutamate on the brain. A number of potential mechanisms have been suggested to explain oxaloacetate-induced neuroprotection. We hypothesize that the primary mechanism by which intravenous oxaloacetate provides neuroprotection is by activation of the blood glutamate-scavenging enzyme glutamate-oxaloacetate transaminase, increasing thereby the driving force for the efflux of excess glutamate from brain interstitial fluids into blood. If so, coadministration of maleate, a glutamate-oxaloacetate transaminase-blocker is expected to prevent the neuroprotective effects of oxaloacetate.A neurological severity score (NSS) was measured 1 hour after closed head injury (CHI) in rats. Then, rats received 30 microL/min/100 g infusion of saline, or 1 mmol/100 g solution of oxaloacetate, maleate, or a mixture of oxaloacetate and maleate. NSS was reassessed at 24 and 48 hour after CHI. Blood glutamate and glucose levels were measured at 0, 60, 90, and 120 minutes.NSS improved significantly at 24 hour (P0.001) and 48 hour (P0.001) only in the rats treated with oxaloacetate. Blood glutamate decreased significantly in the oxaloacetate-treated group at 90 minute (at the conclusion of oxaloacetate administration) (P0.00001), but not in the control, maleate or oxaloacetate+maleate groups. A strong correlation r2=0.86 was found to exist between the percent decrease in blood glutamate levels and percent improvement in NSS.The results of this study demonstrate that the primary mechanism by which oxaloacetate provides neuroprotective activity after CHI is related to its blood glutamate scavenging activity. Management of blood glutamate concentration may have important implications in the treatment of acute brain conditions, including CHI and stroke.