Plasma Glutamate Levels Research Articles

Effect of transcutaneous electrical acupoint stimulation combined with epidural labor analgesia on postpartum depression

To observe the effect of transcutaneous electrical acupoint stimulation (TEAS)combined with epidural analgesia on postpartum depression and to explore its underlying mechanism. One hundred and twenty cases of full-term primiparous women with singleton pregnancy were selected from May 2018 to November 2018 in Jinzhong Maternal and Child Health Hospital. The parturients with labor analgesia requirement were randomly divided into the epidural group and the combination group, and the parturients without labor analgesia requirement were used as the control group, with 40 cases in each group. Patients in the control group did not receive labor analgesia and were treated according to the routine procedures of natural delivery; patients in the epidural group received epidural labor analgesia; patients in the combination group received TEAS at bilateral Hegu(LI4), Sanyinjiao(SP6) and Zusanli(ST36) (2 Hz/100 Hz, the current intensity is gradually increased from 15 mA, and the treatment was performed every 2 h, 20 min each time) combined with epidural labor analgesia. The visual analogue scale (VAS) scores were recorded when the uterine orifice opened to 3, 6, 8, 10 cm. Plasma glutamate was measured using high-performance liquid chromatography before analgesia, at the end of the third stage of labor and 42 days after delivery, and Edinburgh postnatal depression scale (EPDS) score was measured at 42 days after delivery. In comparison with the control group, the VAS score, EPDS score and the incidence of postpartum depression of the epidural group and the combination group were significantly lower(P<0.05), and the combination group had significant decrease than those in epidural group (P<0.05). Immediately before analgesia, there was no statistically significant difference in glutamate levels among the 3 groups (P>0.05). Compared with the control group, at the end of the third stage of labor and 42 days postpartum, the glutamate levels of the epidural group and the combination group were significantly reduced(P<0.05), and the combination group decreased more significantly than the epidural group (P<0.05). TEAS combined with epidural analgesia can reduce the incidence of postpartum depression, possibly by down-regulating plasma glutamate level and relieving of labor pain.

Melatonin exerts a neuroprotective effect against γ-radiation-induced brain injury in the rat through the modulation of neurotransmitters, inflammatory cytokines, oxidative stress, and apoptosis.

The current study aimed to investigate the ameliorative effect of melatonin (MLT) against brain injury in rats undergoing whole-body exposure to γ-radiation. Male Wistar rats were whole-body exposed to 4-Gy γ-radiation from a cesium-137 source. MLT (10 mg/kg) was orally administrated 30 minutes before irradiation and continued once daily for 1 and 7 days after exposure. In the irradiated rats, the plasma levels of glutamate were increased, while the gamma-aminobutyric acid (GABA) levels were decreased, and MLT improved the disturbed glutamate and GABA levels. These effects paralleled an increase in pro-inflammatory cytokines (IL-1b, IL-6, and TNF-a) and C-reactive protein as well as a decrease in IL-10 in the plasma of the irradiated rats. MLT treatment markedly reduced these effects, indicating its anti-inflammatory impact. Immunohistochemical studies demonstrated a remarkable upregulation of caspase-3 and P53 expression, indicating the increased apoptosis in the brain of irradiated rats. MLT significantly downregulated the expression of these parameters compared with that in the irradiated rats, indicating its anti-apoptotic effect. Oxidative stress is developed in the brain as evidenced by increased levels of malondialdehyde; decreased activities of superoxide dismutase, catalase, and glutathione peroxidase; and decreased content of glutathione in the brain. MLT remarkably ameliorated the development of oxidative stress in the brain of the irradiated rats indicating its antioxidant impact. The histopathological results were consistent with the biochemical and immunohistochemical results and showed that MLT remarkably protected the histological structure of brain tissue compared with that in the irradiated rats. In conclusion, MLT showed potential neuroprotective properties by increasing the release of neurotransmitters, antioxidants, and anti-inflammatory factors and reducing pro-inflammatory cytokines and apoptosis in the brain of irradiated rats. MLT can be beneficial in clinical and occupational settings requiring radiation exposure; however, additional studies are required to elucidate its neuroprotective effect in humans.

Higher susceptibility to sunburn is associated with decreased plasma glutamine and increased plasma glutamate levels among US women: An analysis of the Nurses' Health Study I and II

Higher susceptibility to sunburn is associated with decreased plasma glutamine and increased plasma glutamate levels among US women: An analysis of the Nurses' Health Study I and II

A chemical-specific adjustment factor for human interindividual differences in kinetics for glutamates (E620-625)

Use of a default methodology for establishment of a health-based guidance value (HBGV) resulted in a group acceptable daily intake (ADI) for glutamates (E620-625) below the normal dietary glutamate intake, and also lower than the intake of free glutamate by breast fed babies. Use of a chemical-specific adjustment factor (CSAF) may overcome this problem. The present study investigates the interindividual human variability in glutamate plasma and brain levels in order to define a CSAF for the interindividual variation in kinetics, a HKAF, for glutamates. Human clinical data on plasma glutamate levels available from different groups of subjects at Mitsui Memorial Hospital as well as literature data on plasma and brain-related glutamate levels were collected and analysed. The median HKAF value obtained amounted to 2.62–2.74 to 2.33–2.52 for plasma derived values and to 1.68–1.81 for brain derived values. Combining these values with the CSAF for the interspecies differences in kinetics of 1 and the default factors for interspecies and interindividual differences in dynamics of 2.5 and 3.16 results in an overall CSAF of 16–20. Using this CSAF will result in a HBGV for glutamate that is no longer below the acceptable range of oral intake (AROI).

Elevated Circulating Glutamate Is Associated With Subclinical Atherosclerosis Independently of Established Risk Markers: A Cross-Sectional Study.

Elevated plasma glutamate levels are associated with an increased risk of cardiovascular disease (CVD). Because plasma glutamate levels are also strongly associated with visceral adiposity, nonalcoholic fatty liver disease, insulin resistance, and high circulating levels of branched-chain amino acids (BCAAs), it is unknown to what extent elevated circulating glutamate is an independent marker of an increased risk of atherosclerosis. Plasma levels of glutamate and BCAAs were measured in 102 individuals who were precisely phenotyped for body fat mass and distribution (magnetic resonance [MR] tomography), liver fat content (1H-MR spectroscopy), insulin sensitivity (oral glucose tolerance test and hyperinsulinemic, euglycemic clamp [N = 57]), and carotid intima media thickness (cIMT). Plasma glutamate levels, adjusted for age, sex, body fat mass, and visceral fat mass, correlated positively with liver fat content and cIMT (all std β ≥ .22, all P ≤ .023) and negatively with insulin sensitivity (std β ≤ -.31, P ≤ .002). Glutamate levels also were associated with cIMT, independently of additional adjustment for liver fat content, insulin sensitivity and BCAAs levels (std β ≥ .24, P ≤ .02). Furthermore, an independent positive association of glutamate and interleukin-6 (IL-6) levels was observed (N = 50; std β = .39, P = .03). Although glutamate, adjusted for age, sex, body fat mass, and visceral fat mass, also correlated positively with cIMT in this subgroup (std β = .31, P = .02), after additional adjustment for the parameters liver fat content, insulin sensitivity, BCAAs, or IL-6 levels, adjustment for IL-6 most strongly attenuated this relationship (std β = .28, P = .05). Elevated plasma glutamate levels are associated with increased cIMT, independently of established CVD risk factors, and this relationship may in part be explained by IL-6-associated subclinical inflammation.

Altered levels of salivary and plasma pain related markers in temporomandibular disorders

BackgroundDifferent pain syndromes may be characterized by different profiles of mediators reflecting pathophysiological differences, and these alterations may be measured in a simple saliva sample. The aims of the current study were to compare concentration of glutamate, serotonin (5-HT), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and substance P (SP) in saliva and plasma from a well-defined group of patients with chronic temporomandibular disorders myalgia (TMD-myalgia) with a group of pain-free controls, and further investigate the relationship between these markers and clinical characteristics.MethodsPatients diagnosed according to the diagnostic criteria for TMD (n = 39), and matched healthy pain-free controls (n = 39) were included. Stimulated whole saliva and plasma samples were collected in the morning. Glutamate was analysed using a colorimetric assay, and 5-HT and SP were analysed by commercially available ELISA. Levels of NGF and BDNF were determined using multiplex electrochemiluminescence assay panel.ResultsPatients expressed higher salivary and plasma levels of glutamate (saliva: 40.22 ± 13.23 μmol/L; plasma: 30.31 ± 18.73 μmol/L) than controls (saliva: 33.24 ± 11.27 μmol/L; plasma: 20.41 ± 15.96 μmol/L) (p < 0.05). Salivary NGF (0.319 ± 0.261 pg/ml) and BDNF (3.57 ± 1.47 pg/ml) were lower in patients compared to controls (NGF: 0.528 ± 0.477 pg/ml; BDNF 4.62 ± 2.51 pg/ml)(p’s < 0.05). Contrary, plasma BDNF, was higher in patients (263.33 ± 245.13 pg/ml) than controls (151.81 ± 125.90 pg/ml) (p < 0.05). 5-HT was undetectable in saliva. Neither plasma 5-HT, nor SP levels differed between groups. BDNF and NGF concentrations correlated to levels of psychological distress (p < 0.0005).ConclusionThe higher levels of salivary and plasma glutamate in patients with TMD-myalgia compared to controls strengthens its importance in the pathophysiology of TMD-myalgia. However, the lack of correlation to pain levels question its role as a putative biomarker. Patients with TMD-myalgia further had lower levels of salivary NGF and BDNF, but higher plasma BDNF. These results and their correlations to psychological distress warrant further investigations.

Effect of minimally invasive surgery on upper urinary calculi with renal empyema and its effect on renal function

Objective To investigate the clinical effect of minimally invasive surgery in patients with upper urinary calculi and renal empyema and its effect on renal function. Methods Eighty-four patients with upper urinary calculi and renal empyema admitted from April 2016 to March 1818 were enrolled. The random number table was divided into control group and observation group, 42 cases in each group. The control group was treated with ureteroscopic lithotripsy. The observation group was treated with microchannel percutaneous nephrolithotomy. The effect of the patients was evaluated 3 days after surgery. The 7600 automatic biochemical analyzer was used to measure the levels of urea nitrogen, serum creatinine (Scr) and 24 h urine protein (24 h UP) before and after treatment. The enzyme-linked immunosorbent assay was used to measure the two groups before and after surgery. Hypersensitive C-reactive protein, tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6) levels, and endothelin (ET-1) levels, serum of patient was completed by enzyme-linked immunosorbent assay (ELISA) Cortisol (CORT), catecholamine (CA), plasma glutamate (GLU) levels, statistics and re-corded the incidence of stone clearance, septic shock, perirenal abscess, major bleeding and sepsis in the two groups. Effects and effects on renal function in patients. Results The levels of BUN, Scr and 24 h UP in the observation group were lower than those in the control group 3 days after surgery (P 0.05). The incidence of septic shock, perirenal abscess, massive hemorrhage and sepsis after operation was lower in the observation group than in the control group (P<0.05). Conclusions Microchannel percutaneous nephrolithotomy for upper urinary calculi with renal empyema can improve the renal function of patients, reduce inflammatory factors and stress response, and the incidence of postoperative complications is low. It is worthy of popularization and application. Key words: Urinary Calculi; Pyonephrosis; Minimally Invasive Surgical Procedures

Theme 6 Tissue biomarkers

Background: Glutamate excitotoxicity is a longstanding hypothesis in the pathophysiology of ALS. Prior studies have demonstrated increased plasma glutamate levels in ALS patients, which suggest a systemic defect in glutamate metabolism (1). The most abundant amino acid consumed in our diet is glutamate. Studies in healthy human subjects have demonstrated efficient metabolism of dietary glutamate via metabolism by enzymes present in the liver, gut lumen and residential gut bacteria. There is increasing evidence that the gut microbiota has significant CNS effects and intestinal dysbiosis has been found in the ALS transgenic SOD1G93A mouse model (2). If intestinal dysbiosis altered the prevalence of glutamine synthetase (GS) producing bacteria, dietary glutamate homeostasis could be impaired, leading to elevated plasma glutamate levels.Objectives: This study examined the degree of fluctuation in plasma glutamate levels seen with consumption of a protein shake in a cohort of ALS patients and family members from a single ALS center.Methods: Twenty six patients (87% of total cohort followed in the ALS center) underwent measurement of plasma amino acid analysis prior to and 1 hour following consumption of a 75 gm protein shake. A subset of 16 patients went on to receive a probiotic with high GS activity and completed serial protein challenges and amino acid analysis during the study. Ten unaffected family members of ALS patients underwent a similar protein challenge. Glutamate Metabolism Dysfunction (GMD) was defined as >30 umol difference post-prandially compared to fasting, and graded as mild (>30-60), moderate (>60-90) or severe (>90).Results: At baseline, 65.4% (17/26) ALS patients screened were GMD positive, compared to 30% (3/10) of tested family members. The severity of GMD in ALS patients was 41% mild, 29% moderate, 29% severe with only mild severity identified in family members. In the six month treatment phase, 75% (6/8) of patients with stable or improving GMD status saw significant improvements in their ALSFRS-R rate of decline, while 71.4% (5/7) with worsening or remaining severe GMD status experienced worsening of their rate of progression.Discussion and conclusions: Although limited by small sample size, this study does represent an excellent sampling within a single ALS center and is the first of its kind to investigate whether impairment in dietary glutamate metabolism exists in ALS patients. If validated in a larger ALS population, detection of glutamate metabolism dysfunction (GMD) could represent a novel biomarker linked to a potential therapeutic target in ALS patients. Planned microbiome analysis will also help in validating this hypothesis.

P3648Plasma glutamate are increased in non-smoker patients with vasospastic angina pectoris and associated with plasma cystine and antioxidant capacity

Abstract Background Endothelial dysfunction of the coronary arteries caused by oxidative stress plays an important role in the pathogenesis of vasospastic angina pectoris (VSAP). Glutamate, a non-essential amino acid, exerts endothelial dysfunction by oxidative stress production through N-methyl-D-aspartate receptor activation. Besides oxidative stress, decrease of antioxidant may be responsible for endothelial dysfunction. Glutathione (GSH), an important antioxidant, is synthesized from imported cystine through the cystine/glutamate antiporter system (XC-) in association with the export of glutamate. Glutamate also competitively inhibits cystine import into the endothelial cells through the XC-leading to GSH depletion. Thus the extracellular glutamate and cystine are crucial for the intracellular redox status. However, it remains unclear whether glutamate and/or cystine are implicated in the pathogenesis of VSAP. As smoking induces powerful oxidant stresses in the whole body, we investigated plasma glutamate, cystine, oxidative stress markers and antioxidant capacity in non-smoker patients with VSAP. Methods and results Sixty-two consecutive non-smoker patients suspected having VSAP were performed coronary angiograms (CAG). Forty-nine patients who did not show any significant coronary stenosis (&lt;50%) were performed the intracoronary acetylcholine provocation test. Patients were categorized into the VSAP-positive group (n=27) and the VSAP-negative group (n=22) on the basis of test results. Blood samples were collected from the femoral sheath before the CAG. Plasma glutamate, cystine, nitrotyrosine (NT), reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) were measured. The levels of plasma glutamate and cystine in the VSAP-positive group were significantly higher than those in the VSAP-negative group (59.8±25.7 vs 43.5±18.7 nmol/L, p=0.0054, and 35.3±14.2 nmol/L vs 25.2±9.1 nmol/L, p=0.0018, respectively). The levels of plasma glutamate showed significant and positive association with the levels of plasma cystine (r=0.40, p=0.005). There were no significant differences in the levels of NT and d-ROMs as oxidative stress markers, and BAP as an antioxidant capacity between the two groups, respectively. However, the levels of plasma glutamate showed significant and negative association with BAP values (r=−0.3, p=0.038). Conclusions Plasma levels of glutamate were increased in non-smoker patients with VSAP and positively associated with plasma cystine levels and negatively associated with antioxidant capacity, suggesting that plasma glutamate modulate plasma cystine levels and antioxidant capacity through the XC- inhibition, and could be a novel risk factor of VSAP.

Role of Plasma Amino Acids Profiles in Pathogenesis and Prediction of Severity in Patients with Drug Resistant Epilepsy

Background: Abnormal plasma levels of free amino acids may predict the severity in patients with drug resistant epilepsy (PRE), having probability to affect their therapeutic approach. Objectives:We aimed to illuminate the effect of plasma free amino acids (PFAAs) profiles on the etiology of patients with PRE and their contribution on the frequencies of epileptic fits. Patients and Methods:We collected clinical and metabolomic data of 90 subjects; 45 of them were PRE patients, and other 45 age and sex matched healthy controls. Quantitative measurements of PFAAs profiles using SykamAutomatic Amino Acid Analyzer S433, in addition to fasting blood sugar, liver function tests, kidney function tests and lipid profile also, were determined. Results: The plasma levels of glutamate, glycine and Gamma amino butyric acid(GABA) plasma levels were significantly increased in PRE group compared to controls (p˂0.0001),their plasma levels also showed significant increase with increased frequency of epileptic fits. Plasma leucine, phenylalanine, aspartate ,ornithine, citrulline, serine and alanine levels (p˂0.0001) were significantly increased in PRE group in relation to healthy controls. Interestingly, on the other hand, histidine, isoleucine, lysine, threonine and the amino acid derivative taurine levels were significantly decreased in PRE patients compared to healthy controls. Conclusion:Few biomarkers of PRE are available to find the severity and rate of progressionof PRE. The present study showed that altered plasma amino acids and their derivatives may be candidate markers for PRE, help explaining its pathogenesis, and for further researches concerning normalization of the disturbed amino acid/s or its derivative/s (GABA and taurine) in managing PRE patients.

Elimination of glutamate using CRRT for 72 h in patients with post-cardiac arrest syndrome: A randomized clinical pilot trial

AimGlutamine and glutamate are major mediators of secondary brain cell death during post-cardiac arrest syndrome. As there is an equilibrium between brain tissue and plasma concentrations of glutamine and glutamate, their elimination from systemic circulation by extracorporeal blood purification may ultimately lead to reduced secondary cell death in the brain. We hypothesized that systemic glutamine and glutamate can be significantly reduced by continuous venovenous hemodiafiltration (CVVHDF). MethodsThis was a prospective, randomized clinical trial in post cardiac-arrest survivors evaluating standard of care or additional CVVHDF over 72 h immediately after admission. Glutamine and glutamate plasma concentrations were analyzed at eight time points in both groups. Primary endpoint was reduction of glutamine and glutamate plasma concentrations. The trial has been registered at clinical trial.gov (NCT02963298). ResultsIn total, 41 patients were randomized over a period of 12 months (control n = 21, CVVHDF n = 20). The primary aim reduction of glutamine and glutamate plasma concentrations by CVVHDF, was not achieved; both groups-maintained concentrations within a normal range over the study period (glutamate: 4.7–11.1 mg/dL; glutamine: 0.2–3.7 mg/dL). However, post-filter concentrations of glutamine and glutamate in CRRT patients were significantly decreased as compared to pre-filter concentrations (glutamate: pre-filter median 8.85 mg/dL IQR 7.1–9.6; post-filter 0.95 mg/dL IQR 0.5–2; p < 0.001; glutamine: pre-filter 0.7 mg/dL IQR 0.6–1; post-filter 0.2 mg/dL IQR 0–0.2; p < 0.001). ConclusionIn this trial, CVVHDF was not able to statistically significantly lower systemic plasma glutamine and glutamate levels. Post-cardiac arrest patients had plasma glutamine and glutamate levels within the normal range.

Taurine Protects Retinal Cells and Improves Synaptic Connections in Early Diabetic Rats

ABSTRACT Purpose Taurine has long been thought to be involved in retinal protection from retinal degenerative diseases, but the underlying molecular mechanisms remain unclear. Retinal neurodegeneration is an early event in the pathogenesis of diabetic retinopathy (DR) that precedes and participates in the microcirculatory abnormalities that occur in DR. Our objective was to investigate the role and mechanisms of taurine in early diabetic retinas. Methods Eight-week-old STZ-induced diabetic rats and control animals were randomly assigned to receive taurine or vehicle by intraperitoneal injection or by intragastric administration. The retinal function and retinal cell counts were evaluated using an electroretinography (ERG) and immunofluorescence microscopy. Plasma amino acids were measured by ion-exchange chromatography (IEC). The expression levels of retinal taurine transporter (Tau-T), mitochondria-dependent apoptosis-associated genes and reactive gliosis markers were studied by western blotting and immunofluorescence. Pre- and post-synaptic markers (PSD95 and mGluR6) in outer plexiform layer (OPL), and the bipolar cell marker protein kinase C alpha (PKCα) were localized by immunofluorescence. Levels of PSD95 and mGluR6 were determined by quantitative western blot. Results Taurine significantly prevented the reduction of photopic b-wave amplitude and retinal cone cells and ganglion cells loss and maintained the Bcl-2/Bax ratio balance in diabetic rats. Taurine also prevented the upregulation of glial fibrillary acidic protein (GFAP) and reduced retinal reactive gliosis. Taurine reduced plasma glutamate and tyrosine levels, which were elevated in diabetic rats. Moreover, mGluR6 levels reduction detected by western blot and immunofluorescence in diabetic retinas was inhibited and the displacement of mGluR6 in OPL into the inner nuclear layer (INL) detected by immunofluorescence was reduced by Taurine treatment. Conclusion Taurine may protect retinal cells from diabetic attacks by activating Tau-T, reducing retinal reactive gliosis, improving retinal synaptic connections and decreasing retinal cell apoptosis. Thus, taurine treatment may be a novel approach for early DR.

Glutamate interactions with obesity, insulin resistance, cognition and gut microbiota composition.

To investigate the interactions among fecal and plasma glutamate levels, insulin resistance cognition and gut microbiota composition in obese and non-obese subjects. Gut microbiota composition (shotgun) and plasma and fecal glutamate, glutamine and acetate (NMR) were analyzed in a pilot study of obese and non-obese subjects (n = 35). Neuropsychological tests [Trail making test A (TMT-A) and Trail making test B (TMT-B)] scores measured cognitive information about processing speed, mental flexibility and executive function. Trail-making test score was significantly altered in obese compared with non-obese subjects. Fecal glutamate and glutamate/glutamine ratio tended to be lower among obese subjects while fecal glutamate/acetate ratio was negatively associated with BMI and TMT-A scores. Plasma glutamate/acetate ratio was negatively associated with TMT-B. The relative abundance (RA) of some bacterial families influenced glutamate levels, given the positive association of fecal glutamate/glutamine ratio with Corynebacteriaceae, Coriobacteriaceae and Burkholderiaceae RA. In contrast, Streptococaceae RA, that was significantly higher in obese subjects, negatively correlated with fecal glutamate/glutamine ratio. To close the circle, Coriobacteriaceae/Streptococaceae ratio and Corynebacteriaceae/Streptococaceae ratio were associated both with TMT-A scores and fecal glutamate/glutamine ratio. Gut microbiota composition is associated with processing speed and mental flexibility in part through changes in fecal and plasma glutamate metabolism.

Targeting Glutamate Metabolism in Melanoma

The glutamate metabotropic receptor 1 (GRM1) drives oncogenesis when aberrantly activated in melanoma and several other cancers. Metabolomics reveals that patient-derived xenografts with GRM1-positive melanoma tumors exhibit elevated plasma glutamate levels associated with metastatic melanoma in vivo. Stable isotope tracing and GCMS analysis determined that cells expressing GRM1 fuel a substantial fraction of glutamate from glycolytic carbon. Stimulation of GRM1 by glutamate leads to activation of mitogenic signaling pathways, which in turn increases the production of glutamate, fueling autocrine feedback. Implementing a rational drug-targeting strategy, we critically evaluate metabolic bottlenecks in vitro and in vivo. Combined inhibition of glutamate secretion and biosynthesis is an effective rational drug targeting strategy suppressing tumor growth and restricting tumor bioavailability of glutamate.

Memantine ameliorates pulmonary inflammation in a mice model of COPD induced by cigarette smoke combined with LPS

An enhanced chronic inflammatory response in the airways has been regarded as a critical characteristic of chronic obstructive pulmonary disease (COPD). Memantine, an N-methyl-d-aspartate (NMDA) receptors antagonist, has been reported to alleviate lung inflammation. In this study, we investigated the effect and mechanism of memantine on the COPD model induced by cigarette smoke (CS) combined with LPS. Mice and RAW264.7 cells were treated with LPS in the presence or absence of CS. We performed H&E staining to analysis the lung histopathological characteristics. Cytokines (IL-6, TNF-α, and IFN-γ) levels in bronchoalveolar lavage fluid (BALF), lung tissue homogenates and RAW264.7 cell culture medium were determined. Glutamate levels in plasma and culture medium of RAW264.7 were determined. The intracellular Ca2+ flux in RAW264.7 cells was measured by fluo-3 AM staining. The protein levels of NR-1, xCT, ERK1/2, and AKT signaling in the lung tissue and cells were investigated. The result showed that CS and LPS stimulation caused inflammation response, a significant increase in the release of cytokines, including TNF-α, IL-6, and IFN-γ, the elevated release of glutamate and protein levels of NR-1 and xCT, increased Ca2+ influx, and the activation of the ERK1/2 pathway in vitro and in vivo. The above effects of CS and LPS stimulation could be significantly attenuated by memantine treatment. In conclusion, memantine can effectively ameliorate pulmonary inflammation in CS + LPS-induced COPD in mice via reducing NR-1 and xCT expression, glutamate release, Ca2+ influx, and the phosphorylation of Erk1/2. We provided a possible mechanism by which memantine ameliorates COPD in mice.

Role of glutamate and its receptors in migraine with reference to amitriptyline and transcranial magnetic stimulation therapy

Glutamate plays an important role in migraine pathogenesis but there is paucity of studies on glutamate in migraine subtypes, effect of treatment on glutamate levels and the changes in glutamate receptors. In this study we report the glutamate levels and changes in glutamate receptors following amitriptyline (AMT) or repetitive Transcranial Magnetic Stimulation (rTMS) therapy.One hundred and fifty migraine patients having more than 4 migraine attacks per month were included. Thirty patients were treated with AMT and 120 with rTMS; 24 patients received 3 sessions, 36 received single session of rTMS and 60 patients received sham stimulation. The severity of headache was assessed by VAS score, Migraine Index (MI) and frequency of headache. Good outcome was defined by 50% improvement in headache frequency; severity and MI. Plasma glutamate level were measured by enzyme linked immunosorbant assay and relative expression of NR2B and mGluR3 receptors by real time polymerase chain reaction. The changes in these parameters before and after treatment were measured and correlated with the clinical parameters.Glutamate levels (P = 0.006) and NR2B receptor expressions (P < 0.001) were significantly higher in migraine patients compared to the controls. Chronic migraine patients had higher glutamate level (P = 0.05). Glutamate and NR2B receptor declined after treatment (P < 0.001). There was a decline in glutamate levels following rTMS (P = 0.03), sham stimulation (P = 0.05) and AMT treatment (P = 0.003). NR2B receptors also declined after rTMS (P = 0.005) and AMT treatment (P = 0.01). It can be concluded that migraine is associated with high plasma glutamate and NR2B receptor which decline following AMT or rTMS therapy.

Cerebral Osmolytes and Plasma Osmolality in Pregnancy and Preeclampsia: A Proton Magnetic Resonance Spectroscopy Study.

Cerebral complications contribute substantially to mortality in preeclampsia. Pregnancy calls for extensive maternal adaptations, some associated with increased propensity for seizures, but the pathophysiology behind the eclamptic seizures is not fully understood. Plasma osmolality and sodium levels are lowered in pregnancy. This could result in extrusion of cerebral organic osmolytes, including the excitatory neurotransmitter glutamate, but this remains to be determined. The hypothesis of this study was that cerebral levels of organic osmolytes are decreased during pregnancy, and that this decrease is even more pronounced in women with preeclampsia. We used proton magnetic resonance spectroscopy to compare levels of cerebral organic osmolytes, in women with preeclampsia (n = 30), normal pregnancy (n = 32), and nonpregnant controls (n = 16). Cerebral levels of organic osmolytes were further correlated to plasma osmolality and plasma levels of glutamate and sodium. Compared to nonpregnant women, women with normal pregnancy and preeclampsia had lower levels of the cerebral osmolytes, myo-inositol, choline and creatine (P = 0.001 or less), and all these metabolites correlated with each other (P < 0.05). Women with normal pregnancies and preeclampsia had similar levels of osmolytes, except for glutamate, which was significantly lower in preeclampsia. Cerebral and plasma glutamate levels were negatively correlated with each other (P < 0.008), and myo-inositol, choline and creatine levels were all positively correlated with both plasma osmolality and sodium levels (P < 0.05). Our results indicate that pregnancy is associated with extrusion of cerebral organic osmolytes. This includes the excitatory neurotransmitter glutamate, which may be involved in the pathophysiology of seizures in preeclampsia.

Peripheral glutamate and TNF-α levels in patients with intracerebral hemorrhage: Their prognostic values and interactions toward the formation of the edemal volume

ObjectiveWe aimed to evaluate the prognostic values, contribution and interactions of the peripheral blood plasma glutamate and tumor-necrosis factor-α (TNF-α) levels toward the formation of the perifocal edema in patients with intracerebral hemorrhage (ICH). MethodsFifty patients with ICH and fifty healthy controls were included in the study. The peripheral markers were detected by high-sensitivity ELISA. ResultsA highly significant differences in plasma glutamate and TNF-α levels with good separation of their values was detected between patients and healthy controls. The two variables correlated with the severity of the symptoms and the initial volume of the ICH at admission. Both peripheral glutamate and TNF-α levels at admission were estimated as significant predictors for the formation of the perifocal edema five days after ICH; nevertheless, it was shown that they independently contribute to the development of the edema, without effects of interaction and regardless the localization of the ICH. ConclusionsOur results support the idea for the significance of glutamate and TNF-α as peripheral markers for excitotoxicity and inflammation in ICH patients. The developed multiple regression model for prediction of the development of the edema could be beneficial in decision making between conservative treatment and surgical intervention in the clinical practice.

Plasma amino acid profile in major depressive disorder: Analyses in two independent case-control sample sets

Some amino acids act as neurotransmitters themselves, or are precursors of neurotransmitters. Previous studies reported inconsistent results regarding their changes in blood in major depressive disorder (MDD), which prompted us to examine plasma levels of amino acids and related molecules in two independent case-control sample sets. In total, 511 subjects were recruited. Sample set A consisted of 164 patients with MDD (147 currently depressed [dMDD]; 17 in remission, DSM-IV) and 217 healthy controls. Sample set B consisted of 65 patients (51 dMDD; 14 in remission) and 65 controls. Plasma amino acid levels were measured using high-performance liquid chromatography for set A and liquid chromatography/mass spectrometry for set B. We further analyzed the relationships between plasma amino acid levels and clinical variables. In sample set A, plasma asparagine, histidine+1-methylhistidine, methionine, phenylalanine, tryptophan, and tyrosine levels were decreased, while plasma glutamate and phosphoethanolamine were elevated in dMDD compared to controls (all P < 0.0005), even after correcting for multiple testing. Plasma leucine levels were associated with “psychic anxiety.” In sample set B, glutamate and methionine levels were also altered in the same direction to that in sample set A (both P < 0.05). In the integrative analysis, plasma glutamate and methionine levels were found to be significantly associated with the diagnosis of MDD with small to medium effect sizes (both P < 1.0E-6). In conclusion, several amino acids and related molecules were altered in patients with MDD. Decreased methionine and increased glutamate levels were found consistently in the two sample sets, suggesting their involvement in MDD. Further investigations are warranted on the possible role of amino acids in the pathophysiology of MDD.

Reduced Mismatch Negativity is Associated with Increased Plasma Level of Glutamate in First-episode Psychosis

Reduced amplitude of mismatch negativity (MMN) is one of the more promising biological markers of schizophrenia. This finding holds true in both early and chronic phases of the disorder, and is compatible with the glutamatergic dysfunction hypothesis. To further establish MMN as a biomarker of aberrant glutamatergic neurotransmission, an exploration for an association with blood levels of glutamatergic amino acids is an important next step. Despite a large body of work investigating MMN in schizophrenia, no previous studies have undertaken this endeavor. Nineteen patients with first-episode psychosis (FEP), 21 ultra-high risk individuals (UHR), and 16 healthy controls (HC) participated in the study. The MMNs in response to duration change (dMMN) and frequency change (fMMN) were measured. The fasting plasma levels of glutamate, glutamine, glycine, D-serine, and L-serine were measured. dMMN amplitudes were significantly reduced in FEP and UHR, compared to HC. The plasma levels of glutamate of FEP were significantly higher than those of HC. Higher plasma levels of glutamate were associated with smaller dMMN amplitudes in the FEP and HC groups. These findings are compatible with the hypothesis that MMN is a useful biological marker of aberrant glutamatergic neurotransmission in the early stages of schizophrenia.