Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Following permanent middle cerebral artery occlusion, extracellular penumbral glutamate levels, measured by a real-time glutamate electrode, increased in two different patterns. In 7/11 rats, glutamate increased from baseline levels of 19+/-4 (mean+/-SEM) to 208+/-29 microM and then declined towards baseline levels. Blood flow in the penumbral area declined to 30% of pre-ischemic levels with recovery to 60 and 70% of baseline values by 3 and 6 h, respectively. Four of 11 rats in the study also exhibited late peaks of glutamate release (120+/-40 microM ) 2 h after the onset of ischemia. There were no changes in the EEG recordings or cerebral blood flow during these late glutamate peaks.
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PMID:Real-time measurement of glutamate release from the ischemic penumbra of the rat cerebral cortex using a focal middle cerebral artery occlusion model. 1116 32

Our group recently demonstrated that autoimmune T cells directed against central nervous system-associated myelin antigens protect neurons from secondary degeneration. We further showed that the synthetic peptide copolymer 1 (Cop-1), known to suppress experimental autoimmune encephalomyelitis, can be safely substituted for the natural myelin antigen in both passive and active immunization for neuroprotection of the injured optic nerve. Here we attempted to determine whether similar immunizations are protective from retinal ganglion cell loss resulting from a direct biochemical insult caused, for example, by glutamate (a major mediator of degeneration in acute and chronic optic nerve insults) and in a rat model of ocular hypertension. Passive immunization with T cells reactive to myelin basic protein or active immunization with myelin oligodendrocyte glycoprotein-derived peptide, although neuroprotective after optic nerve injury, was ineffective against glutamate toxicity in mice and rats. In contrast, the number of surviving retinal ganglion cells per square millimeter in glutamate-injected retinas was significantly larger in mice immunized 10 days previously with Cop-1 emulsified in complete Freund's adjuvant than in mice injected with PBS in the same adjuvant (2,133 +/- 270 and 1,329 +/- 121, respectively, mean +/- SEM; P < 0.02). A similar pattern was observed when mice were immunized on the day of glutamate injection (1,777 +/- 101 compared with 1,414 +/- 36; P < 0.05), but not when they were immunized 48 h later. These findings suggest that protection from glutamate toxicity requires reinforcement of the immune system by antigens that are different from those associated with myelin. The use of Cop-1 apparently circumvents this antigen specificity barrier. In the rat ocular hypertension model, which simulates glaucoma, immunization with Cop-1 significantly reduced the retinal ganglion cell loss from 27.8% +/- 6.8% to 4.3% +/- 1.6%, without affecting the intraocular pressure. This study may point the way to a therapy for glaucoma, a neurodegenerative disease of the optic nerve often associated with increased intraocular pressure, as well as for acute and chronic degenerative disorders in which glutamate is a prominent participant.
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PMID:Vaccination for protection of retinal ganglion cells against death from glutamate cytotoxicity and ocular hypertension: implications for glaucoma. 1124 90

Glutamate is considered to be the primary neurotransmitter in the retinohypothalamic tract (RHT), which delivers photic information from the retina to the suprachiasmatic nucleus (SCN), the locus of the mammalian circadian pacemaker. However, substance P (SP) also has been suggested to play a role in retinohypothalamic transmission. In this study, we sought evidence that SP from the RHT contributes to photic resetting of the circadian pacemaker and further explored the possible interaction of SP with glutamate in this process. In rat hypothalamic slices cut parasagittally, electrical stimulation of the optic nerve in early and late subjective night produced a phase delay (2.4 +/- 0.5 hr; mean +/- SEM) and advance (2.6 +/- 0.3 hr) of the circadian rhythm of SCN neuronal firing activity, respectively. The SP antagonist L-703,606 (10 microm) applied to the slices during the nerve stimulation completely blocked the phase shifts. Likewise, a cocktail of NMDA (2-amino-5-phosphonopentanoic acid, 50 microm) and non-NMDA (6,7-dinitroquinoxaline-2,3-dione, 10 microm) antagonists completely blocked the shifts. Exogenous application of SP (1 microm) or glutamate (100 microm) to the slices in early subjective night produced a phase delay ( approximately 3 hr) of the circadian firing activity rhythm of SCN neurons. Coapplication of the NMDA and non-NMDA antagonist cocktail (as well as L-703,606) resulted in a complete blockade of the SP-induced phase delay, whereas L-703,606 (10 microm) had no effect on the glutamate-induced delay. These results suggest that SP, as well as glutamate, has a critical role in photic resetting. Furthermore, the results suggest that the two agonists act in series, SP working upstream of glutamate.
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PMID:Substance p plays a critical role in photic resetting of the circadian pacemaker in the rat hypothalamus. 1135 89

At the large excitatory calyx of Held synapse, the quantal size during an evoked EPSC and the number of active zones contributing to transmission are not known. We developed a nonstationary variant of EPSC fluctuation analysis to determine these quantal parameters. AMPA receptor-mediated EPSCs were recorded in slices of young (postnatal 8-10 d) rats after afferent fiber stimulation, delivered in trains to induce synaptic depression. The means and the variances of EPSC amplitudes were calculated across trains for each stimulus number. During 10 Hz trains at 2 mm Ca(2+) concentration ([Ca(2+)]), we found linear EPSC variance-mean relationships, with a slope that was in good agreement with the quantal size obtained from amplitude distributions of spontaneous miniature EPSCs. At high release probability with 10 or 15 mm [Ca(2+)], competitive antagonists were used to partially block EPSCs. Under these conditions, the EPSC variance-mean plots could be fitted with parabolas, giving estimates of quantal size and of the binomial parameter N. With the rapidly dissociating antagonist kynurenic acid, quantal sizes were larger than with a slowly dissociating antagonist, suggesting that the effective glutamate concentration was increased at high release probability. Considering the possibility of multivesicular release and moderate saturation of postsynaptic AMPA receptors, we conclude that the binomial parameter N (637 +/- 117; mean +/- SEM) represents an upper limit estimate of the number of functional active zones. We estimate that during normal synaptic transmission, the probability of vesicle fusion at single active zones is in the range of 0.25-0.4.
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PMID:Estimation of quantal size and number of functional active zones at the calyx of Held synapse by nonstationary EPSC variance analysis. 1158 62

Hypoglycemic brain damage has been associated with high levels of the excitatory amino acids (EAA) aspartate and glutamate in the newborn and adult. We hypothesized that newborn piglet EAA would be different from those of older pigs when stressed with severe insulin-induced hypoglycemia (<30 mg/dl). Brain EAA were measured in piglets and adolescent pigs via microdialysis. Eleven of 12 newborn normoglycemic piglets had no detectable baseline levels (<0.5 microM) of EAA, while pigs had aspartate and glutamate concentrations of 1.78 +/- 0.44 and 3.43 +/- 1.14 microM (mean +/- SEM), respectively. Piglet aspartate and glutamate concentrations reached but did not significantly exceed normoglycemic pig levels after 2 h with plasma glucose values < or =20 mg/ml. Elevations in EAA were only detected in piglets whose EEG activity ceased. Aspartate and glutamate concentrations did not increase in insulin-treated pigs nor in control animals. We speculate that newborns with blood glucose less than clinically acceptable values (35 mg/dl) may be protected from EAA-associated neuronal damage during acute hypoglycemia. Lower normoglycemic and hypoglycemic levels of EAA in newborns when compared to older pigs provide this protection.
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PMID:Brain excitatory amino acid concentrations are lower in the neonatal pig: a buffer against excitotoxicity? 1164 55

Talampanel [(R)-7-acetyl-5-(4-aminophenyl)-8,9-dihydro-8-methyl-7H-1,3-dioxolo[4,5-h][2,3] benzodiazepine] is an orally active noncompetitive antagonist of the AMPA subtype of glutamate excitatory amino acid receptors. The purpose of this study was to determine whether treatment with talampanel would protect in a rat model of traumatic brain injury (TBI). Twenty-four hours prior to TBI, a fluid-percussion interface was positioned parasagittally over the right cerebral cortex. On the following day, fasted rats were anesthetized with 3% halothane, 70% nitrous oxide, and a balance of oxygen; mechanically ventilated and physiologically regulated; and subjected to right parieto-occipital parasagittal fluid-percussion injury (1.5-2.0 atm). The agent (talampanel, bolus infusion of 4 mg/kg followed by infusion of 4 mg/kg/h over 72 h) or vehicle was administered i.v. starting at either 30 min or 3 h after trauma. Seven days after TBI, brains were perfusion-fixed, coronal sections at various levels were digitized, and contusion areas were measured. Treatment with talampanel, when instituted 30 min after trauma, significantly reduced total contusion area compared to vehicle-treated rats (0.54 +/- 0.25 vs. 1.79 +/- 0.42 mm2, respectively). When talampanel treatment was begun at 3 h, the neuroprotective effect of the drug was lost. In addition, treatment with talampanel starting at 30 min significantly attenuated neuronal damage in all three subsectors of the hippocampal CA1 sector compared to vehicle-treated rats (normal-neuron counts, right (ipsilateral) medial CA1: 80.3 +/- 2.0 [talampanel] vs. 66.3 +/- 2.1 [vehicle] (mean +/- SEM); middle CA1: 71.5 +/- 2.0 vs. 60.3 +/- 2.2; lateral CA1: 74.5 +/- 3.0 vs. 63.0 +/- 3.2, respectively). By contrast, when talampanel treatment was begun at 3 h, normal pyramidal-neuron counts were almost identical in both groups. Our findings document that talampanel therapy instituted 30 min after trauma significantly reduces histological damage.
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PMID:Talampanel, a novel noncompetitive AMPA antagonist, is neuroprotective after traumatic brain injury in rats. 1168 90

The circadian pacemaker housed in the suprachiasmatic nucleus (SCN) synchronizes daily sleep-wake cycles, presumably by modulating the sleep-wake regulatory system, including ventrolateral preoptic area (VLPO) neurons. We used whole-cell patch-clamp recording to study the projections from the SCN to the VLPO in horizontal slices of rat hypothalamus. Single-pulse stimulation of the SCN region elicited postsynaptic currents (PSCs) in 20 of 66 neurons (30%) recorded within the VLPO region as verified by intracellular biocytin labelling. At a holding potential of -60 mV, the evoked PSCs had an amplitude of 17.6 +/- 3.2 pA (SEM) and a latency of 6.3 +/- 0.5 ms (n = 10). There was a trend for simple excitatory postsynaptic currents (EPSCs) to be evoked in the VLPO cluster, simple inhibitory postsynaptic currents (IPSCs) in the extended VLPO, and a combination of EPSCs and IPSCs in both regions. IPSCs were blocked reversibly by bicuculline (10 microm, n = 11). In both the presence and absence of bicuculline, EPSCs had fast and slow components that were blocked by 6,7-dinitroquinoxaline-2,3-dione (DNQX; 10 microm; n = 7), and (+/-)3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 10 microm, n = 6), respectively. Reversal potentials for the evoked IPSCs and EPSCs were consistent with mediation via GABAA and ionotropic glutamate receptors, respectively. These results suggest that the SCN region provides both inhibitory and excitatory inputs to single VLPO neurons, which are mediated, respectively, by GABAA receptors and by both non-NMDA and NMDA glutamate receptors. These projections may play important roles in conveying circadian input to systems in the preoptic area that regulate sleep and waking.
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PMID:Electrophysiological analysis of suprachiasmatic nucleus projections to the ventrolateral preoptic area in the rat. 1170 55

We have previously shown that the addition of gum arabic (GA) to oral rehydration solution (ORS) enhances water and electrolyte absorption during jejunal perfusion in rats under anesthesia. This study investigates whether GA by oral administration could be equally effective in rats. Isotonic solutions containing 25 g/L GA (AG), or without GA (A0) were administered via oral tube to lightly anesthetized adult female rats. Similar experiments were conducted with hypertonic solutions containing no GA (B0), or either 10 (B10) or 50 g/L GA (B50). Blood concentrations of sodium, glucose, glutamate, zinc, and tritiated water were determined at 0, 15, 30, 60, 90, 120, and 180 minutes, and results between treatments were compared. Administration of the isotonic, GA-containing solution (AG) resulted in a higher blood zinc level than with the isotonic GA-free solution (A0) from 15 minutes throughout 180 minutes. Blood zinc at 15 minutes (means +/- SEM) was as follows: for A0: 69.3 +/- 2.0, for AG: 83.4 +/- 3.5 nmol/L, P=0.002. At 180 minutes, A0: 52.6 +/- 1.8; AG: 68.1 +/- 4.6 nmol/L, P=0.004. The corresponding areas under the curve (AUC) were as follows: for A0: 10,737 +/- 214; for AG: 13,919 +/- 765 nmol x min/L, P<0.001). Glucose, glutamate, sodium, and tritiated water body distribution presented no differences in blood concentrations. For sodium and tritiated water body distribution, there was a significant time effect (P<0.0001). In hypertonic solutions, blood zinc levels declined over time, possibly due to their osmotic, counter-absorptive action, thus obscuring possible opposite effects of GA. GA appears to be an effective enhancer of zinc absorption when orally administered in isotonic solutions to laboratory animals. This proabsorptive capacity could be attributed to some of the physicochemical and biochemical properties of GA and suggest possible applications of GA in liquid formulas and solid food preparations.
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PMID:Proabsorptive effect of gum arabic in isotonic solutions orally administered to rats: effect on zinc and other solutes. 1502 1

Recently, decreased glutamate (Glu) and reduced glutathione (GSH) levels were reported in the quadriceps femoris of patients with chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate whether Glu and GSH levels are also modified in the diaphragm of these patients. Nine male COPD patients (forced expiratory volume in one second (FEV1) range 28-68% of the predicted value) and seven male patients with normal pulmonary function (mean +/- SD FEV1 86 +/- 3% pred) submitted to thoracotomy were included. Biopsy specimens were taken from the diaphragm (both groups) and the quadriceps femoris (COPD group alone) in order to assess fibre size, myosin heavy chain expression, GSH levels and amino acid profile. The COPD group was characterised by preserved fibre size, a higher proportion of type I fibres (mean +/- SEM 70 +/- 3 versus 26 +/- 4%), and higher Glu and GSH content in the diaphragm compared to the quadriceps muscle. However, Glu and GSH levels were similar in diaphragm from the COPD and control groups. Glu level correlated with GSH level in both muscles. No significant correlation was found between Glu or GSH level and fibre size or proportions. This study shows that glutamate and reduced glutathione levels are preserved in the diaphragm of chronic obstructive pulmonary disease patients. Alterations in glutamate and reduced glutathione metabolism are muscle-specific in chronic obstructive pulmonary disease, affecting the quadriceps femoris but not the diaphragm. Glutamate and reduced glutathione levels are strongly interrelated in both muscles, independent of fibre type distribution and fibre size.
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PMID:Glutathione and glutamate levels in the diaphragm of patients with chronic obstructive pulmonary disease. 1508 52

Using an antiserum directed against glutamate, we have analyzed the distribution of glutamate-like immunoreactive neurons in the terminal abdominal ganglion of the crayfish Procambarus clarkii. Approximately 160 central neurons (157 +/- 8; mean +/- SEM, n = 8) showed positive glutamate-like immunoreactivity, which represents approximately 25% of the total number of neurons in the terminal ganglion. Using a combination of intracellular staining with the marker Lucifer yellow and immunocytochemical staining has shown that most excitatory motor neurons are glutamatergic and that glutamate acts as an excitatory transmitter at peripheral neuromuscular junctions. Seven of 10 identified spiking local interneurons and only 2 of 19 identified ascending interneurons, showed positive immunoreactivity. Our observation that inhibitory spiking interneurons were immunopositive, whereas excitatory ascending interneurons were immunonegative, indicates that glutamate is likely to act as an inhibitory neurotransmitter within the central nervous system. Local pressure injection of L-glutamate into the neuropil of the ganglion caused a hyperpolarization of the membrane potentials of many interneurons. gamma-Aminobutyric acid (GABA)ergic posterolateral nonspiking interneurons and the bilateral nonspiking interneuron LDS showed no glutamate-like immunoreactivity, whereas non-GABAergic anterolateral III nonspiking interneurons showed glutamate-like immunoreactivity. Thus, not only GABA but also glutamate are used in parallel as inhibitory neurotransmitters at central synapses.
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PMID:Distribution of glutamatergic immunoreactive neurons in the terminal abdominal ganglion of the crayfish. 1515 82


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