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1.
目的 观察托吡酯对大鼠脑缺血时海马细胞外液兴奋性氨基酸释放的影响 ,探讨托吡酯在脑梗死治疗中应用的可能性。方法 建立大鼠脑缺血模型 ,给予托吡酯干预 ,应用微透析方法观察大鼠海马细胞外液中兴奋性氨基酸及抑制性氨基酸的变化。结果 脑缺血后兴奋性氨基酸和抑制性氨基酸的释放均增加 ,而给予托吡酯干预后 ,脑缺血后兴奋性氨基酸的释放明显减少 ,而抑制性氨基酸的释放明显增加。结论 托吡酯能有效地抑制脑缺血中兴奋性氨基酸的释放 ,能减轻兴奋性氨基酸的毒性作用。  相似文献   

2.
It is uncertain whether a brief hypoxic exposure exerts long lasting effects on central nervous system amino acid neurotransmission. The purpose of this study was to test the hypothesis that a short period of hypoxia would affect release of excitatory and inhibitory amino acids during subsequent bicuculline-induced seizure. Utilizing in vivo microdialysis in cerebral cortex of rabbits, we observed no significant increase in extracellular fluid (ECF) concentrations of the excitatory amino acids, glutamate and aspartate, or the inhibitory amino acids, GABA and taurine, during a 30-min exposure to hypoxia (FiO2 = 0.08). In addition, there was no significant change in these amino acids during uncomplicated seizure. However, when seizure was complicated by a preceding period of hypoxia, there was a marked and progressive rise in both excitatory and inhibitory amino acids in ECF. We conclude that a short period of hypoxia, which itself does not cause changes in ECF concentrations of excitatory amino acids, may nonetheless contribute to neuronal injury by altering the levels of ECF amino acids during a subsequent insult.  相似文献   

3.
Alteration in extracellular amino acids after traumatic spinal cord injury   总被引:11,自引:0,他引:11  
It has recently been demonstrated that N-methyl-D-aspartate antagonists limit tissue damage after spinal cord trauma, implicating excitatory amino acids in the secondary injury response. To determine whether spinal cord trauma alters the concentrations of extracellular amino acids, microdialysis was conducted in spinal cord during and after administration of impact trauma. Extracellular concentrations of excitatory, inhibitory, and nontransmitter amino acids were elevated after trauma, with the degree of increase related to severity of injury. Moderate trauma resulted in an immediate but transient increase (200-400%) in the extracellular levels of all amino acids measured. Severe trauma produced a more prolonged and significant increase (400-630%) in the concentrations of extracellular amino acids, including aspartate and glutamate. These results are consistent with the hypothesis that excitatory amino acids may contribute to delayed tissue injury after central nervous system trauma.  相似文献   

4.
A recent study describing two epileptic patients with brain cysts has suggested that elevated concentrations of excitatory amino acids in cysts may play a role in induction and maintenance of epileptogenesis [Epilepsy Res. 28 (1997) 245]. Here, we report that only in 3 out of 22 patients with brain cysts undergoing brain surgery cyst fluids displayed highly increased amounts of the excitatory amino acids aspartate and/or glutamate. Two of these patients experienced epileptic seizures prior to neurosurgical intervention. Thus, highly increased excitatory amino acid levels are present only in a subset of patients with brain cysts. Our observation that one patient with highly increased glutamate and aspartate concentrations in the cyst did not display seizures or typical epileptiform potentials in the EEG questions that these excitatory amino acids in the cyst fluid are directly involved in epileptogenicity. This patient displayed an increased level of adenosine in the cyst fluid, which is known to have anticonvulsant properties and might provide protection from seizures. In summary, there is no evidence for a close correlation between excitatory amino acids in brain cysts and the occurrence of seizures.  相似文献   

5.
Do endogenous excitatory amino acids influence striatal dopamine release?   总被引:3,自引:0,他引:3  
In vivo microdialysis techniques were used to examine whether endogenous excitatory amino acids exert a tonic facilitatory influence on striatal dopamine release. Local application of NMDA and non-NMDA antagonists at 10 microM was without an effect on basal dopamine release while 100 microM and 1 mM of these drugs significantly enhanced the release. Our findings do not support the idea that excitatory amino acids have a tonic excitatory effect on striatal dopamine release.  相似文献   

6.
目的 探讨神经节苷脂(GM-1)对体外培养SH-SY5Y细胞兴奋性氨基酸毒性损伤的保护作用。方法 采用细胞培养法,以神经母细胞瘤SH-SY5Y细胞系为材料,制备兴奋性氨基酸Glu毒性损伤的离体细胞损伤模型。通过细胞形态学观察、MTT法测定细胞存活率观察不同浓度及不同时间GM-1对上述损伤细胞的保护及治疗作用。结果 GM-1可增强SH-SY5Y细胞的存活,抑制兴奋性氨基酸对细胞的损伤。与损伤组相比GM-1治疗组均好于损伤组,且GM-1高浓度组好于低浓度组。GM-1对损伤SH-SY5Y细胞MTT代谢率的影响显示,相同浓度GM-1作用不同时间相比较12h优于6h,24h与12h无明显差异。结论 GM-1可促进神经细胞生存,对神经细胞具有明显保护作用。  相似文献   

7.
McAdoo DJ  Robak G  Xu GY  Hughes MG 《Brain research》2000,854(1-2):152-157
The hypothesis that release of adenosine following spinal cord injury (SCI) may provide neuroprotective feedback is explored. Consistent with this hypothesis, substantial release of adenosine, estimated to reach 100 microM in the extracellular space, was detected by microdialysis sampling immediately following contusion SCI. There is also considerable release of excitatory amino acids following SCI. The latter was not affected by administration of the general adenosine receptor antagonist theophylline and the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine, implying that the adenosine released following SCI does not significantly influence the release of neurotoxic amino acids. Administration of the concentration of glutamate released upon SCI into the spinal cord caused only about 1% as much release of adenosine as did injury, evidence that elevated excitatory amino acids do not elicit an appreciable fraction of the release of adenosine that follows SCI. Results obtained suggest that release of endogenous adenosine is not neuroprotective by blocking release of excitatory amino acids following SCI.  相似文献   

8.
The release of glutamate, aspartate, glutamine and asparagine upon impact injury to the rat spinal cord was characterized by sample collection from the site of injury by microdialysis. Injury caused dramatic and long-lasting increases in the concentrations of the excitatory amino acids. Determination of the relationship between unperturbed extracellular levels and the levels of amino acids in the collected fluids indicates that the concentrations of these amino acids were probably high enough to kill neurons for longer than one hour following impact injury to the spinal cord. Increases in the concentrations of the metabolically related non-neurotransmitters asparagine and glutamine were considerably smaller. The latter observations suggest that much of the increase in levels of the excitatory amino acids resulted from neuronal activity rather than from simple damage.  相似文献   

9.
OBJECTIVES: Increases in the extracellular concentration of the excitatory amino acids glutamate and aspartate during cerebral ischaemia in patients are well recognised. Less emphasis has been placed on the concentrations of the inhibitory amino acid neurotransmitters, notably gamma-amino-butyric acid (GABA), despite evidence from animal studies that GABA may act as a neuroprotectant in models of ischaemia. The objective of this study was to investigate the concentrations of various excitatory, inhibitory and non-transmitter amino acids under basal conditions and during periods of cerebral ischaemia in patients with head injury or a subarachnoid haemorrhage. METHODS: Cerebral microdialysis was established in 12 patients with head injury (n=7) or subarachnoid haemorrhage (n=5). Analysis was performed using high performance liquid chromatography for a total of 19 (excitatory, inhibitory and non-transmitter) amino acids. Patients were monitored in neurointensive care or during aneurysm clipping. RESULTS: During stable periods of monitoring the concentrations of amino acids were relatively constant enabling basal values to be established. In six patients, cerebral ischaemia was associated with increases (up to 1350 fold) in the concentration of GABA, in addition to the glutamate and aspartate. Parallel increases in the concentration of glutamate and GABA were found (r=0.71, p<0.005). CONCLUSIONS: The results suggest that, in the human brain, acute cerebral ischaemia is not accompanied by an imbalance between excitatory and inhibitory amino acids, but by an increase in all neurotransmitter amino acids. These findings concur with the animal models of ischaemia and raise the possibility of an endogenous GABA mediated neuroprotective mechanism in humans.  相似文献   

10.
The human immunodeficiency virus coat protein gp120 injures central mammalian neurons both in vitro and in vivo , and this observation may contribute, at least in part, to the neurological dysfunction associated with the acquired immunodeficiency syndrome. Recent work suggests that gp 120 mediates neuronal damage predominantly via an indirect route involving activation of brain macrophages. We have previously shown that the stimulation of N -methyl-D-aspartate receptors by excitatory amino acids is essential for the neuronal injury observed with gp 120. Here we show that gp 120 impairs astrocyte uptake of excitatory amino acids and the excess glutamate thus engendered may contribute to the increased neuronal damage. We also studied the mechanism whereby gp 120 inhibits the uptake of excitatory amino acids by astrocytes. We present data suggesting that at least one pathway involves a direct effect of gp120 on macrophages, which in turn release arachidonic acid, a known inhibitor of excitatory amino acid uptake by astrocytes. Our findings suggest that the observed effects on glia and neurons of gp120 may be secondary, at least in part, to its initial activation of macrophages.  相似文献   

11.
We have investigated the action of excitatory amino acids and their antagonists on spontaneous motor activity produced by an isolated preparation of the chick lumbosacral cord. Bath application of N-methyl-DL-aspartic acid (NMDA) or D-glutamate increased the occurrence and duration of spontaneous episodes of motor activity. Both NMDA-induced and spontaneous activity were reversibly inhibited by several excitatory amino acid antagonists including 2-amino-5-phosphono valeric acid and gamma-D-glutamyl glycine in a dose-dependent manner. These results suggest that motor activity in the chick spinal cord may be regulated by the release of endogenous excitatory amino acids from spinal interneurons.  相似文献   

12.
Summary It has been suggested that dopamine release can be evoked by excitatory amino acids acting on dopaminergic terminals, as well as by the classical process of impulse-evoked exocytosis. We used in vivo microdialysis to examine whether endogenous excitatory amino acids locally evoke dopamine efflux under basal conditions. Infusion of N-methyl-d-aspartate (NMDA) or kainate into the neostriatum increased extracellular dopamine, and this effect was blocked by co-infusion of 2-amino-5-phosphonovalerate (APV) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), respectively. However, neither these antagonists nor kynurenate decreased extracellular dopamine when administered alone. In contrast, infusion of tetrodotoxin into the medial forebrain bundle reduced extracellular dopamine to below the limit of detection of our assay. These and other findings reviewed in this report suggest to us that extracellular dopamine in the neostriatum is not stimulated locally by endogenous excitatory amino acids.  相似文献   

13.
An iontophoretic study was made of the interaction of kynurenic acid with excitatory amino acids in the hippocampus and with the commissural input from the contralateral hippocampus in the rat. The results showed that kynurenic acid was an effective blocker of synaptic transmission in the hippocampus in vivo, adding further support to the idea that an excitatory amino acid is involved in neurotransmission in this structure. In addition there was an increase in the specificity of kynurenate as an antagonist of excitatory amino acids in the hippocampus compared with neocortex, with much more activity being shown toward the NMDA-preferring rather than the quisqualic acid-preferring receptor. Kynurenic acid was also able to distinguish partially between quinolinic acid and NMDA, supporting the possibility that two types of NMDA/quinolinate receptors exist in the hippocampus.  相似文献   

14.
目的:研究脑反复缺血后海马细胞外液氨基酸和单胺递质及其代谢产物的变化规律。方法:采用Pulsinelli和Brierley4血管闭塞的方法,使鼠脑反复缺血,海马微管透极与高压液相电化学检测,观察细胞外谷氨酸(Glu),天门冬氨酸(Asp),谷氨酰胺,牛磺酸、丙氨酸,丝氨酸,多巴胺(DA),5-羟色胺(5-HT)及其代谢产物浓度的变化。结果:缺血期,Glu和Asp骤然增高50倍和30倍。缺血期DA和5-HT含量分别增加30倍和50倍,随后逐渐下降,再灌注100min恢复到基线水平,与此同时,其酸性代谢产物3,4-二羟苯乙酸(DOPAC),高香草酸(HVA),5-羟吲哚乙酸(5-HIAA)在缺血期明显下降。结论:缺血期海马细胞外液兴奋性氨基酸和单胺递质急剧大量释放并触发膜离子通道改变。Ca^+超载,自由基反应,共同  相似文献   

15.
It is well established that excitatory amino acid neurotransmitters are extensively liberated during ischemia and that they have neurotoxic properties contributing to neuronal injury. To study changes in the liberation of excitatory and other amino acids during cerebral ischemia, we measured their extracellular concentrations and related them to blood flow levels and electrophysiologic activity (electrocorticogram and auditory evoked potentials) before and for up to 2 hours after multiple cerebral vessel occlusion in 14 anesthetized cats. Blood flow levels between 0 and 43 ml/100 g/min were reached. Concentrations of the excitatory amino acid neurotransmitters increased most (aspartate 10-fold, glutamate 30-fold, and gamma-aminobutyric acid 300-fold compared with control values) below a blood flow threshold of 20 ml/100 g/min. The total power of the electrocorticogram and the amplitude of the auditory evoked potentials were affected below the same blood flow threshold. In contrast, concentrations of the nontransmitter amino acids taurine, alanine, asparagine, serine, and glutamine increased 1.5-5-fold as blood flow decreased, while concentrations of the essential amino acids phenylalanine, valine, leucine, and isoleucine did not change during cerebral ischemia. The great increases in concentrations of the excitatory amino acid neurotransmitters below a blood flow threshold close to that for functional disturbance is in accordance with the role of these amino acids in ischemic cell damage. Their release at blood flow levels compatible with cell survival and the increase in their concentrations with severity and duration of cerebral ischemia imply that excitotoxic antagonists may have potential as therapeutic agents.  相似文献   

16.
Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis   总被引:19,自引:0,他引:19  
Recently, the excitatory amino acid neurotransmitter glutamate was implicated in the pathogenesis of a variety of chronic degenerative neurological diseases in humans and animals. This report describes abnormalities in excitatory amino acids in the central nervous system of 18 patients with amyotrophic lateral sclerosis (ALS). The concentration of the excitatory amino acids glutamate and aspartate in the cerebrospinal fluid were increased significantly (p less than 0.01) by 100 to 200% in patients with ALS. Similarly, the concentrations of the excitatory neuropeptide N-acetyl-aspartyl glutamate and its metabolite, N-acetyl-aspartate, were elevated twofold to threefold in the cerebrospinal fluid from the patients. There was no relationship between amino acid concentrations and duration of disease, clinical impairment, or patient age. In the ventral horns of the cervical region of the spinal cord, the level of N-acetyl-aspartyl glutamate and N-acetyl-aspartate was decreased by 60% (p less than 0.05) and 40% (p less than 0.05), respectively, in 8 patients with ALS. Choline acetyltransferase activity was also diminished by 35% in the ventral horn consistent with motor neuron loss. We conclude that excitatory amino acid metabolism is altered in patients with ALS. Based on neurodegenerative disease models, these changes may play a role in motor neuron loss in ALS.  相似文献   

17.
Free Amino Acids in Cerebrospinal Fluid from Patients with Infantile Spasms   总被引:3,自引:2,他引:1  
Profiles of free amino acids in cerebrospinal fluid (CSF) were determined by high-performance liquid chromatography for 20 nonneurologic control patients and 12 patients with infantile spasms. Statistical comparisons showed significantly elevated levels of lysine (p less than 0.001) and the excitatory neurotransmitter, glutamate, (p less than 0.01) for the infantile spasms group as compared to the nonneurologic control group. When the infantile spasms patients were subdivided according to the presence or absence of etiologic associations, highly elevated amino acid levels were observed only in CSF from patients of the symptomatic subgroup. The idiopathic subgroup showed levels of free amino acids that were not statistically different from those of the nonneurologic control group. These results indicate that while abnormalities of amino acid metabolism often accompany infantile spasms, no specific pattern of the major free amino acids in CSF appears to be directly related to this seizure disorder. Elevated levels of the excitatory amino acids, aspartate and glutamate, do not necessarily accompany infantile spasms, and in this study were only observed in symptomatic patients.  相似文献   

18.
Unilateral microinjections (0.20 μl) of excitatory amino acids were made into the midbrain of freely moving rats. Injections made within the midbrain periaqueductal grey matter (PAG) consistently elicited reactions characteristic of defensive behaviour (i.e. explosive jumps, freezing, upright postures), whereas injections made in the tegmentum bordering the PAG did not as reliably elicit such behaviour. As injections of excitatory amino acids depolarize cell bodies but not axons, the results suggest that a population of neurones whose excitation elicits these reactions is found primarily within the midbrain PAG of the rat. Furthermore, the data suggested that such neurones may be localized preferentially within the caudal half of the midbrain PAG. Injections of the GABA antagonist, bicuculline methiodide, at many of the same midbrain sites produced behaviour similar to that elicited by excitatory amino acids indicating a possible GABAergic modulation of these same PAG-mediated reactions. It also was observed following unilateral injection into the PAG, of either the excitatory amino acid, l-aspartic acid or bicuculline, that defensive behaviour was elicited by touching the rat on the body or snout contralateral but not ipsilateral to the injection site. This suggests that the induction of defensive behaviour by unilateral PAG stimulation is due, at least in part, to lateralized alterations in sensorimotor responsiveness.  相似文献   

19.
Unilateral microinjections (0.20 microliter) of excitatory amino acids were made into the midbrain of freely moving rats. Injections made within the midbrain periaqueductal grey matter (PAG) consistently elicited reactions characteristic of defensive behaviour (i.e. explosive jumps, freezing, upright postures), whereas injections made in the tegmentum bordering the PAG did not as reliably elicit such behaviour. As injections of excitatory amino acids depolarize cell bodies but not axons, the results suggest that a population of neurones whose excitation elicits these reactions is found primarily within the midbrain PAG of the rat. Furthermore, the data suggested that such neurones may be localized preferentially within the caudal half of the midbrain PAG. Injections of the GABA antagonist, bicuculline methiodide, at many of the same midbrain sites produced behaviour similar to that elicited by excitatory amino acids indicating a possible GABAergic modulation of these same PAG-mediated reactions. It also was observed following unilateral injection into the PAG, of either the excitatory amino acid, L-aspartic acid or bicuculline, that defensive behaviour was elicited by touching the rat on the body or snout contralateral but not ipsilateral to the injection site. This suggests that the induction of defensive behaviour by unilateral PAG stimulation is due, at least in part, to lateralized alterations in sensorimotor responsiveness.  相似文献   

20.
Recently much attention has been paid to excitatory amino acids in seizure susceptibility and induction. In order to examine the relationship between epilepsy, especially seizure induction, and excitatory amino acids, we examined sequential change in content of excitatory amino acids in the epileptic focus by microdialysis system in a cat amygdaloid kindling model. Fifteen crossbred adult cats divided into three groups: a sham operation group (Sh) as the control, just after stage 4 group (S4), and just after stage 6 seizure group (S6). Under halothane anesthesia, Microdialysis probe was inserted to the kindled focus, the right amygdala, and glutamate and aspartate contents of extracellular fluid were measured from 15 minutes prior to 30 minutes after seizure by high performance liquid chromatography (HPLC). The probe was perfused with artificial cerebrospinal fluid at a flow rate of 2 microliters/min for 5 minutes. Before seizure, glutamate and aspartate concentration showed no significant changes in the S4 and S6 group compared with the Sh group. But after seizure, glutamate concentration was significantly higher in the S4 and S6 group temporally, while aspartate concentration was higher only in the S6 group temporally. Based on the results that the release of glutamate and aspartate do not change in seizure susceptibility, that glutamate is released in partial seizure, and that glutamate and aspartate are released in generalized seizure from the epileptic focus, excitatory amino acids are involved in seizure induction in a cat amygdaloid kindling.  相似文献   

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