Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamic acid is the principal excitatory neurotransmitter in the mammalian central nervous system. Glutamic acid binds to a variety of excitatory amino acid receptors, which are ligand-gated ion channels. It is activation of these receptors that leads to depolarisation and neuronal excitation. In normal synaptic functioning, activation of excitatory amino acid receptors is transitory. However, if, for any reason, receptor activation becomes excessive or prolonged, the target neurones become damaged and eventually die. This process of neuronal death is called excitotoxicity and appears to involve sustained elevations of intracellular calcium levels. Impairment of neuronal energy metabolism may sensitise neurones to excitotoxic cell death. The principle of excitotoxicity has been well-established experimentally, both in in vitro systems and in vivo, following administration of excitatory amino acids into the nervous system. A role for excitotoxicity in the aetiology or progression of several human neurodegenerative diseases has been proposed, which has stimulated much research recently. This has led to the hope that compounds that interfere with glutamatergic neurotransmission may be of clinical benefit in treating such diseases. However, except in the case of a few very rare conditions, direct evidence for a pathogenic role for excitotoxicity in neurological disease is missing. Much attention has been directed at obtaining evidence for a role for excitotoxicity in the neurological sequelae of stroke, and there now seems to be little doubt that such a process is indeed a determining factor in the extent of the lesions observed. Several clinical trials have evaluated the potential of antiglutamate drugs to improve outcome following acute ischaemic stroke, but to date, the results of these have been disappointing. In amyotrophic lateral sclerosis, neurolathyrism, and human immunodeficiency virus dementia complex, several lines of circumstantial evidence suggest that excitotoxicity may contribute to the pathogenic process. An antiglutamate drug, riluzole, recently has been shown to provide some therapeutic benefit in the treatment of amyotrophic lateral sclerosis. Parkinson's disease and Huntington's disease are examples of neurodegenerative diseases where mitochondrial dysfunction may sensitise specific populations of neurones to excitotoxicity from synaptic glutamic acid. The first clinical trials aimed at providing neuroprotection with antiglutamate drugs are currently in progress for these two diseases.
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PMID:The role of excitotoxicity in neurodegenerative disease: implications for therapy. 1033 61

A method for chromatographic analysis of human serum amino acids is proposed. Orthophthalic aldehyde in combination with 2-mercaptoethanol or sodium sulfite as a reagent for amino acid transfer into derivatives permits the identification of 15 amino acids within the framework of a single chromatographic system with an isocratic elution regimen. Glutamic acid, asparagine, serine, glutamine, histidine, taurine, alanine, arginine, methionine, isoleucin, ornithine, leucin, phenylalanine, lysin, and triptophane were measured in the sera of healthy donors and patients with ischemic stroke.
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PMID:[A quantitative analysis of amino acids in blood serum by isocratic reverse-phase HPLC]. 1050 20

Glutamic acid is the major excitatory neurotransmitter in the mammalian central nervous system (CNS). Specific receptors bind glutamate and some of these when activated open an integral ion channel and are thus known as ionotropic receptors. Within the ionotropic family of glutamate receptors, three major subtypes have been identified using classical specific agonist activation, selective competitive antagonists together with their structural heterogeneity. These receptors have thus been named N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and kainate receptors. The NMDA receptor has sites in addition to its agonist-binding site and these seem to either positively or negatively modulate the agonist effect. The NMDA receptor also is unique in that another amino acid, glycine, acts as a co-agonist with glutamate. Changes in glutamate transmission have been associated with a number of CNS pathologies; these include, acute stroke, chronic neurodegeneration, chronic pain, depression, drug dependency, epilepsy, Parkinson's Disease and schizophrenia.
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PMID:Excitatory amino acid agonists and antagonists: pharmacology and therapeutic applications. 1081 62

The efficacy of pre-, intra-, and postoperative prevention of hemodynamic disorders by creatinine phosphate, cytochrome C, and glutamic acid was evaluated in 61 coronary patients with decreased myocardial contractility. All these agents exerted a positive inotropic effect in coronary patients with ejection fraction below 0.4, increasing the stroke volume and left-ventricular ejection fraction without modifying heart rate. Glutamic acid is not recommended for preoperative treatment, because it increases oxygen consumption by the myocardium above the reserve potential of the coronary bed. Cytochrome C is the most effective drug for preoperative treatment. Intraoperative preischemic protection of the myocardium by cytochrome C in coronary patients during high risk operations prevents the development of unfavorable hemodynamic complications during induction and maintenance of anesthesia before artificial circulation, provides favorable recovery of cardiac activity, decreases the incidence of severe arrhythmias, promotes a rapid and full-value recovery of myocardial contractile function after ischemia, and decreases the incidence of acute heart failure.
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PMID:[Prevention of disorders of myocardial contractile function in patients with ischemic heart disease during aortocoronary shunting]. 1145 65

Glutamic acid (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system (CNS) where it is involved in the physiological regulation of different processes. It has been well established that excessive endogenous Glu is associated with many acute and chronic neurodegenerative disorders such as cerebral ischemia, epilepsy, amiotrophic lateral sclerosis (ALS), Parkinson's and Alzheimer's diseases. In addition to the classical competitive glutamate receptor (GluR) antagonists, much effort has been directed toward the development of many different non-competitive antagonists of these receptors and, among them, compounds blocking the glycine site on the NMDA receptor complex (Gly/NMDA) have been widely investigated. Many Gly/NMDA receptor antagonists showed to be potential therapeutic agents in many neurological diseases such as stroke, epilepsy and neuropathic pain. Some of them, endowed also with favourable physicochemical properties and low secondary undesiderable effects, reached clinical trials.
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PMID:Competitive Gly/NMDA receptor antagonists. 1671 19

Excess l-glutamate (glutamate) levels in brain interstitial and cerebrospinal fluids (ISF and CSF, respectively) are the hallmark of several neurodegenerative conditions such as stroke, traumatic brain injury or amyotrophic lateral sclerosis. Its removal could prevent the glutamate excitotoxicity that causes long-lasting neurological deficits. As in previous studies, we have established the role of blood glutamate levels in brain neuroprotection, we have now investigated the contribution of the peripheral organs to the homeostasis of glutamate in blood. We have administered naive rats with intravenous injections of either l-[1-(14)C] Glutamic acid (l-[1-(14)C] Glu), l-[G-(3)H] Glutamic acid (l-[G-(3)H] Glu) or d-[2,3-(3)H] Aspartic acid (d-[2,3-(3)H] Asp), a non-metabolized analog of glutamate, and have followed their distribution into peripheral organs. We have observed that the decay of the radioactivity associated with l-[1-(14)C] Glu and l-[G-(3)H] Glu was faster than that associated with glutamate non-metabolized analog, d-[2,3-(3)H] Asp. l-[1-(14)C] Glu was subjected in blood to a rapid decarboxylation with the loss of (14)CO(2). The three major sequestrating organs, serving as depots for the eliminated glutamate and/or its metabolites were skeletal muscle, liver and gut, contributing together 92% or 87% of total l-[U-(14)C] Glu or d-[2,3-(3)H] Asp radioactivity capture. l-[U-(14)C] Glu and d-[2,3-(3)H] Asp showed a different organ sequestration pattern. We conclude that glutamate is rapidly eliminated from the blood into peripheral tissues, mainly in non-metabolized form. The liver plays a central role in glutamate metabolism and serves as an origin for glutamate metabolites that redistribute into skeletal muscle and gut. The findings of this study suggest now that pharmacological manipulations that reduce the liver glutamate release rate or cause a boosting of the skeletal muscle glutamate pumping rate are likely to cause brain neuroprotection.
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PMID:Distribution of radiolabeled l-glutamate and d-aspartate from blood into peripheral tissues in naive rats: significance for brain neuroprotection. 2069 57