To explore the possibility that an elevation of glutamate in the vitreous might be associated with the microvascular compromise of the optic nerve, endothelin1(ET-1)in a dosage of 0.1 microgram/day(5 rabbits)or balanced salt solution(4 rabbits) was delivered to the perineural region of the anterior optic nerve by osmotically driven minipumps for 2 weeks. Vitreous specimens were obtained and the iramino acid contents were determined by high performance liquid chromatography. There was a statistically significant elevation(p<0.05)in the vitreous concentrations of glutamate(264%+/-41%), aspartate(269%+/-31%)and glycine(232%+/-26%)in the eyes subjected to ET-1 when compared with that of eyes in control group. Administration of ET-1 to the microvasculature of the optic nerve leads to the elevation of glutamate, aspartate, and glycine concentrations in the vitreous. These results suggest that the increase of excitatory amino acids in the vitreous may play a role in the neuronal damage induced by optic nerve ischemia.
Aspartic Acid ; Chromatography, Liquid ; Endothelin-1 ; Excitatory Amino Acids ; Glutamic Acid* ; Glycine ; Microvessels ; Neurons ; Optic Nerve* ; Optic Neuropathy, Ischemic* ; Vitreous Body*

PURPOSE: Glutamate and aspartate are the excitatory amino acid neurotransmitters and NMDA (N-methyl-D-aspartate) is one of their major receptors. NMDA agonist may sti mulate serotonergic nervous system that inhibit the penile erection as well as induce the penile erection. We investigate the effects of NMDA agonist on serotonin release from hippocampus. MATERIALS AND METHODS: The slices of hippocampus were incubated in a buffer con taining 0.1mM [(3)H]5-hydroxytryptamine (5-HT) for uptake in the male rat. The release of 5-HT into the buffer during each 10 minutes period was measured and the radio activities in each buffer and the tissue were counted. After 50 min from the initiation, NMDA agonist were administered at 6th and 7th 10 min period respectively. The changes of 5-HT release were expressed as percent values compared to the 5th 10 min period. Tetrodotoxin was used to determine the possible involvement of interneuron on the action of these neurotransmitters. RESULTS: A steady release of 5-HT was observed up to 100 minutes after the rapid release during the first 40 minutes. Treatment of tetrodotoxin (10(-6)M) did not change the spontaneous release of 5-HT. The 5-HT released during 10 and 20 minutes of NMDA agonist (10(-4M)) treatment significantly higher than those of control group. The increase of 5-HT release by NMDA agonist was blocked by pretreatment with tetro dotoxin. The release of 5-HT was increased by NMDA agonist and this response was blocked by tetrodotoxin. CONCLUSIONS: NMDA agonist increases the release of 5-HT through the activation of the interneurons and these results suggest that NMDA agonist may stimulate the serotonergic nervous system that inhibit the penile erection as well as inducing the penile erection.
Animals ; Aspartic Acid ; Excitatory Amino Acids ; Glutamic Acid ; Hippocampus* ; Humans ; Interneurons ; Male ; N-Methylaspartate* ; Nervous System ; Neurotransmitter Agents ; Penile Erection ; Rats* ; Serotonin* ; Tetrodotoxin

Electrical stimulation of the cerebellar fastigial nucleus(FN) increases cerebral blood flow(CBF) and reduces brain damage after focal cerebral ischemia. The authors studied whether the neuroprotection elicited from electrical stimulation of the cerebellar FN is attibutable to the elevation in regional CBF(rCBF) or reduction in release of excitatory amino acid sprague-Dawley rats were anesthtized with a mixture of halothane(3% for the indurction and 1% for maintenance) and oxygen and artificially ventilated through a tracheal cannula. Arterial pressure, blood gases and body temperature were monitored. The middle cerebral artery(MCA) was occluded distal to the lenticulostriate branches. The FN was then for 2 hours, over the regions corresponding to the ischemic core and penumbra. Postiischemic release of glutamate and aspartate were measured by microdialysis for 2 hours at the same site of measurement of rCBF. Infarct volume was determined 8 hours later in 2,3,5-triphenyl tetrazolium chloride(TTC)-stained sections FN stimulation(n=12) increased mean arterial pressure by 28+/-16mmHg. In nonstimulated control rats(n=12), mean AP was not changed significantly during the experimental procedures. Compared with nonstimulated animal, stimulation of FN for 1 hour following MCA occlusion siginficantly increased rCBF in ischemic core and penumbra by 53.6% and 67.6% respectively. And the volume of infarction decreased by 42% at 8 hours after MCA occlusion. The concentration of glutamate and aspartate in ischemic core after MCA occlusion increased both in the control group(to 12.2+/-3.3 folds and 10.4+/-4.1 folds respectively) and in the stimulation group(10.5+/-2.8 and 11.2+/-4.1 folds, respectively). The concentration of glutamate and aspartate in penumbra did change significantly neither in the control group(to 2.5+/-1.3 folds and 1.8+/-0.6 folds respectively) nor in the stimulation group(1.9+/-0.5 folds and 2.1+/-0.4 folds, respectively). There was no significant difference between the two groups.
Animals ; Arterial Pressure ; Aspartic Acid ; Body Temperature ; Brain ; Brain Ischemia ; Catheters ; Electric Stimulation ; Excitatory Amino Acids ; Gases ; Glutamic Acid ; Infarction ; Microdialysis ; Oxygen ; Rats* ; Rats, Sprague-Dawley

The author has examined the effect of cortical spreading depression(CSD) on the changes in extracellular concetration of aspartate and glutamate in the neocortex of anesthetized rats using microdialysis and high performance liquid chromatography(HPLC). The rats were prepared by halothane anesthesia and artificial ventilation. Rats were placed in a stereotaxic frame, and craniotomies were performed over the frontal and parietal cortexes on one side. The CSD was elicited by local application of KCI-soaked small pellets to the frontal cortex. The CSD was monitored by the changes of direct current(DC) potential in the parietal cortex. The microdialysis probe was implanted in the anterior part of the parietal cortex. Amino acids were analyzed by HPLC and fluorescence detection. Baseline concentration of the aspartate was 34.9+/-15.9nM and that of glutamate was 189.8+/-29.1nM(mean standard deviation). The perfusate for analysis was obtained 30 minutes after the beginning of the 300mM KCl induced CSD. Aspartate was found to increase to 146+/-55% baseline, glutamate up to 173+/-30% baseline(mean standard deviation). The increment of glutamate was statistically significant(p<0.05). Then 2M KCI-doaked pellets were applied for more frequent CSD amd the samples were collected. Aspartate increased up to 258+/-97% baseline, glutamate up to 174+/-57% baseline(mean standard deviation), The increment of glutamate and aspartate accompanying 2M KCI induced CSD were also statistically significant(p<0.05). These data suggest that the excitatory amino acids were released during the CSD and this may explain the various aspects of CSD that could contribute to the secondary neuronal damage in the compromised nerve cell.
Amino Acids ; Anesthesia ; Animals ; Aspartic Acid* ; Cerebral Cortex* ; Chromatography, High Pressure Liquid ; Cortical Spreading Depression* ; Craniotomy ; Excitatory Amino Acids ; Fluorescence ; Glutamic Acid* ; Halothane ; Microdialysis ; Neocortex ; Neurons ; Rabeprazole ; Rats* ; Ventilation

Recent researches on ALS pathogenesis are focusing on abnormal immunological factors, excitotoxic substances, neurotrophic factors, and oxidative stress. It is well known that glutamate and aspartate are major putative excitatory neurotransmitters and possess excitotoxic properties that lead to neuronal death. In this study the authors checked the plasma level of amino acids in ALS and control groups and tried to understand any association between excitotoxic amino acids and sporadic ALS. The concentration of amino acids was measured by the HPLC method in the fasting plasma of fifteen ALS and nine control subjects. When we evaluated 19 amino acids or their metabolites, none showed significant difference between ALS and control groups. The mean concentrations of glutamic acid in ALS and control groups were 42.3+26.7 mmol/L and 57.4+17.0 mmol/L respectively, which showed no significant difference (p>O. 05). It was not possible to compare the level of aspartic acid in ALS and control groups as the levels were very low in individuals of both groups. In conclusion, authors could not note any significant correlations between sporadic ALS and excitotoxic substances, such as glutamate and aspartate. However, further studies m the excitotoxic levels in cerebrospinal fluid, spinal cord and brain, could be helpful to understand the overexcitation character of motor neuron by excitatory amino acids.
Amino Acids* ; Amyotrophic Lateral Sclerosis* ; Aspartic Acid ; Brain ; Cerebrospinal Fluid ; Chromatography, High Pressure Liquid ; Excitatory Amino Acids ; Fasting ; Glutamic Acid ; Immunologic Factors ; Motor Neurons ; Nerve Growth Factors ; Neurons ; Neurotransmitter Agents ; Oxidative Stress ; Plasma ; Spinal Cord

The purpose of this study was, first, to devise a new model for topical application of excitatory amino acids(EAAs) to rat cerebral cortex that successfully and repeatdly initiate the cortical spreading depression(CSD). Then, by using this model, six major EAAs that are known to act on single or multiple subtypes of EAA receptor were examined; glutamate, kainate, aspartate, N-methyl-D-aspartate(NMDA), quisqualate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazoie-proprite(AMPA). Through the model, with a cone-shaped well buried in 1.5mm depth of the cerebral cortex, these chemical agents were topically applied to the cortical gray matter. A total of 50 Sprague-Dawley rats were used and divided into seven groups including the sham group. Doses of each EAA between 10(-7) and 10(-4)M concentrations were escalated for triggering the CSD and its rate of consistency in triggering was also evaluated. In the overall results. CSDs were repeatedly initiated in all experimental groups with relatively consistent rates. Duration of CSDs were 1-4 minutes(mean 2.2+/-1.4) and amplitudes were 20-40mV. Effective dose(50)(ED(50)), that trigger over 50% of CSD was 10(-5)M(n=8) for glutamate, 10(-7)M(n=8) for aspartate, 10(-5)M(n=7) for AMPA, 10(-5)M(n=7) for quisqualate, and 10(-4)M(n=7) for NMDA and kainate group. Among those acting on the single receptor, AMPA was shown to be the most effective in triggering CSD, and NMDA, and kainate were in descending orders. Aspartate that was known to act on multiple EAA receptors, showed the highest rate of triggering CSD among all groups, but glutamate, known to act on all receptors of its subtypes, showed the most consistent rate of triggering CSD at dose escalation. These results revealed that those EAA acting on multiple receptors, namely aspartate and glutamate, showed the highest and most consistent rate of triggering CSD. Among those acting on single channel of receptors. AMPA was the most effective, although its consistency and rate of triggering of CSD was somewhat lower than.
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid ; Animals ; Aspartic Acid ; Cerebral Cortex ; Cortical Spreading Depression* ; Excitatory Amino Acids* ; Glutamic Acid ; Kainic Acid ; N-Methylaspartate ; Quisqualic Acid ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA

OBJECTIVETo observe the effects of polydatin on dynamic changes of excitatory amino acids in cerebrospinal fluid and water content of brain tissue of cerebral hemorrhage rats. And to discuss the therapeutic action and mechanisms of polydatin on brain hemorrhagic injured rats.

METHODA quantitative determination method of Asp and Glu was established by microdialysis-HPLC. The cerebral hemorrhage model in rats was induced by local injection of type VII collagenase. The dynamic changes of Asp and Glu in cerebrospinal fluid were observed on 0, 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 h of cerebral hemorrhage rats, and then the water content of brain tissue was detected.

RESULTThe content of Asp and Glu increased rapidly within 24 h after cerebral hemorrhage, and to the highest in 24 h, then decreased gradually. Compared with the cerebral hemorrhage model group, the content of Asp and Glu increased slowly in polydatin group, and there were significant differences in 12-72 h and 6-84 h (P < 0.01, P < 0.05), but there was no significant difference after 84 h and 96 h. Compared with sham group, water content of brain tissue significantly higher in model group, while significantly lower (P < 0.01) in polydatin group.

CONCLUSIONPolydatin can inhibit increasing content of Asp and Glu in cerebrospinal fluid dynamics, and significantly inhibit cerebral edema of cerebral hemorrhage rats. It shows that the mechanisms of anti-cerebral hemorrhage injury of polydatin may be related to increasing of excitatory amino acids after cerebral hemorrhage.

Animals ; Aspartic Acid ; cerebrospinal fluid ; Cerebral Hemorrhage ; cerebrospinal fluid ; drug therapy ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Excitatory Amino Acids ; cerebrospinal fluid ; Glucosides ; therapeutic use ; Glutamic Acid ; cerebrospinal fluid ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Stilbenes ; therapeutic use

BACKGROUNDThe mechanisms underlying postoperative pain remain unclear. Neurotransmitters of excitatory and inhibitory amino acids play an important role in the transmission and modulation of pain in the spinal dorsal horn. This study aimed to investigate the changes of release of excitatory and inhibitory amino acids in the spinal cord during postoperative pain and to provide a novel theoretical basis for postoperative pain management.

METHODSLoop microdialysis catheters were implanted subarachnoidally via the atlanto-occipital membrane in 16 healthy Sprague-Dawley rats. All rats without neural deficits were divided into two groups, Group A and Group B, following 5 days of recovery. The tubes for microdialysis were connected and 25 microl microdialysate sample for baseline value was collected after one-hour washout in each rat. A plantar incision in the right hind paws of rats in Group A were performed under 1.2% isoflurane. All rats in Group B were only anesthetized by 1.2% isoflurane for the same duration. The microdialysate samples were collected at 3 hours, 1 day, 2 days and 3 days after the incision (or isoflurane anesthesia in Group B) in both groups. The cumulative pain scores were also assessed at the above time-points. The amino acids in the microdialysate samples were tested using high performance liquid chromatography.

RESULTSWithin Group A, the release of aspartate and glutamate at 3 hours after the incision was significantly higher than the baseline values and the release of glycine at 1 day after the incision significantly increased compared with the baseline values (P < 0.01). Within Group B, the release of neurotransmitters at each time point had no significant difference compared with the baseline values (P > 0.05). The release of aspartate and glutamate at 3 hours after the incision in Group A was significantly higher than that in Group B (P < 0.01). The release of glycine at 1 day after the incision in Group A significantly increased compared with Group B (P < 0.01). The cumulative pain scores at 3 hours, 1 day and 2 days after the incision in Group A were significantly higher than those in Group B (P < 0.01).

CONCLUSIONSThe release of the excitatory amino acids occurs in the early phase of postoperative pain and might not be involved in the maintenance of pain in a rat model of incision pain. The release of inhibitory glycine lagged behind the excitatory amino acids. The implication of inhibitory glycine release remained to be established further.

Animals ; Aspartic Acid ; secretion ; Excitatory Amino Acids ; cerebrospinal fluid ; secretion ; Glutamic Acid ; secretion ; Glycine ; secretion ; Male ; Microdialysis ; Neurotransmitter Agents ; secretion ; Pain, Postoperative ; metabolism ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; secretion

Introduction: It was aimed to investigate the effect of chronic toluene exposure on amino acid neurotransmitters in the rat brain, corpus striatum. METHODS: Twenty four male Sprague-Dawley rats were divided into one of three groups, control, acute, and chronic. Each groups was for the microdialysis to estimate the changes of amino acid neurotransmitters, aspartate, glutamate, and citrulline before, during, and after 3,000 ppm toluene exposure for 2 hours. RESULTS: The results were as follows; 1) Aspartate and glutamate concentration were generally decreased in the toluene inhalation groups compared with the control group and more significantly decreased in chronic inhalation group than other groups. 2) Citrulline that expressed the activity of nitric oxide synthase and taurine as an inhibitory amino acid showed no significant differences between all groups. Based on these results, it is suggested that the decreasing excitatory amino acids, aspartate and glutamate, are partly contributed to the toxic mechanisms of toluene in rat brain.
Animals ; Aspartic Acid ; Brain* ; Citrulline ; Control Groups ; Corpus Striatum ; Excitatory Amino Acids ; Glutamic Acid ; Humans ; Inhalation ; Male ; Microdialysis ; Neurotransmitter Agents* ; Nitric Oxide Synthase ; Rats* ; Rats, Sprague-Dawley ; Taurine ; Toluene*

BACKGROUNDS: The importance of toxic extracellular levels of excitatory amino acids, as well as of high extracellular levels of inhibitory amino acids, is considered to be related with the pathophysiology of neuronal cell loss during cerebral ischemia. METHODS: The extracellular concentration of glutamate, glycine, and taurine in the hippocampus were determined during and after transient global ischemia in the New Zealand white rabbit. Because the cerebroprotective effects of profound hypothermia are well known and clinically widely used,we used the hypothermia group as an experimental group compared with normothermic control group in the experimental protocol. To derive a quantitative descriptor reflecting the magnitude of amino acid neurotransmitter changes with ischemia, we defined the 'taurine index' as: [glutamate]x[glycine]/[taurine]. RESULTS: Ischemia led to large increases in both excitatory (glutamate and glycine) and inhibitory amino acids(taurine) in the normothermic group. Taurine index was increased during ischemia and after reperfusion and had a close relationship with the severity of ischemia-induced neuronal damage. CONCLUSIONS: The taurine index appears to be a reliable biochemical marker to determine the severity of ischemic injury.
Amino Acids ; Biomarkers ; Brain Ischemia ; Excitatory Amino Acids ; Glutamic Acid ; Glycine ; Hippocampus ; Hypothermia ; Ischemia ; Neurons ; Neurotransmitter Agents ; New Zealand ; Reperfusion ; Subject Headings ; Taurine*