Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bilateral occlusion of common carotid arteries in Mongolian gerbils was produced for the periods (up to 15 min) which were shown to be totally reversible. There was an initial increase of cyclic AMP and GABA levels and enhanced activities of adenylate cyclase and glutamate decarboxylase, as well as the reduction of norepinephrine level and decreased activities of monoamine oxidase, GABA-transaminase and Na+-K+-ATPase. Following these changes, decreased concentration of dopamine, serotinin and glutamate were found. The activities of total protein kinase and acetylcholinesterase were found to be reduced after longer periods of short-term ischemia. The data are consistent with the concept of increased non-controled release of putative neurotransmitters in ischemia.
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PMID:Alterations of putative neurotransmitters and enzymes during ischemia in gerbil cerebral cortex. 3 75

A uniform, predictable pattern of cellular abnormalities is seen after complete, irreversible ischemic injury to the central nervous system. This is in contrast to the heterogeneous, multifocal picture which characterizes incomplete ischemia. The range of abnormalities in neuronal soma after an arterial occlusion changes considerably as a function of time and site. There is no single pattern of neuronal alteration that can be ascribed exclusively to ischemia. Red neurons are a relatively late (about 18 h) indicator of ischemia and are seen only in areas where blood supply is marginal. In addition to depletion of high-energy-phosphate reserves, brain ischemia results in characteristic alterations of amino acid concentrations in the ischemic tissue. Glutamate, glutamine, and aspartate either decrease or remain constant while alanine increases. Proportional decreases in the former three amino acids may be explained by simple dilution due to edema. Increases in alanine relative to glutamate and aspartate may be utilized as a biochemical index of perfusion to various brain regions.
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PMID:Neuronal ischemic injury: light microscopy, ultrastructure and biochemistry. 9 17

N-dimethyl propranolol (UM-272) has been shown to protect the heart from injury produced by ischemia. In the present study we examined the effects of UM-272 on the function of isolated rabbit cardiac mitochondria and microsomes. Concentrations of 13 micrometers or below were without effect on these organelles. UM-272 (130 micrometers) significantly decreased respiratory control of mitochondria utilizing glutamate plus malate, or succinate, as substrates. At 1.3 mM, UM-272 increased the initial rate of basal oxygen consumption, and decreased the rate of ADP-stimulated respiration. UM-272 was slightly more potent than d,1-propranolol. At a concentration of 1.3 mM, UM-272 significantly decreased the rate and maximum amount of 45CaCl2 accumulated by microsomes in the presence of ATP and oxalate. Concentrations of drug that suppress cellular metabolism are close to those required to prevent ischemic injury. We suggest that sarcolemmal and intracellular actions of the drug which help to depress oxygen demand and ATP utilization may account for part of the drug's protective effects.
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PMID:Effects of N-dimethyl propranolol (UM-272) on isolated cardiac mitochondria and microsomes. 49 13

Electron transport in tissue cubes, isolated mitochondria and submitochondria particles were examined as a function of ischemic time. It was found that electron transport remains active in all systems beyond the 2 hour ischemic time interval. The NADH stimulated respiration, however, declined after 2 hours of ischemia in ASU (Ammonia-Sephadex-Urea) particles followed by respiration with matrix-located dehydrogenases tested by substrates such as glutamate, alpha-ketoglutarate and pyruvate plus malate. Succinate dependent respiration remains active at control levels. In contrast proton gradient reveals changes in two phases: Phase A is characterized by gradually increasing gradient without valinomycin and by a rapidly declining gradient with valinomycin in the medium. Phase B is characterized by a declining proton gradient with or without valinomycin. It is suggested that the alteration of the proton gradient between 1 and 2 hours ischemia is an important factor contributing to irreversible cell injury.
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PMID:Studies on the pathogenesis of ischemic cell injury. VII. Proton gradient and respiration of renal tissue cubes, renal mitochondrial and submitochondrial particles following ischemic cell injury. 60 84

This study examines indices of respiratory function in mitochondria prepared from transiently ischemic myocardium that had been reperfused in order to evaluate the validity of performing early surgical revascularization procedures. Experiments were performed in pigs with temporary ligation (15-80 min) of an anterior descending coronary artery followed by a 2-hr reperfusion period. Mitochondria preparations were studied simultaneously from normal and reperfused mitochondria in malate and glutamate substrates using the polarographic method. Results revealed a marked decrease of oxygen consumption of mitochondria from reperfused myocardium with relative preservation of oxidative phosphorylation (near normal ADP/O ratio). These results are compatible with a block in electron transport, a theory which was further supported by the data obtained using dinitrophenol as an uncoupler. Additional studies suggested the block was located at site I in the electron transport chain since mitochondrial oxygen consumption, including ATP-linked oxygen consumption, was enhanced by the use of succinate in combination with glutamate. The abnormal mitochondrial function observed is probably due to ischemia persisting despite reperfusion.
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PMID:Impairment of mitochondrial function following reperfusion of acutely ischemic myocardium. 121 42

Tracer kinetic studies on the effect of i.v. infused adrenaline and angiotensin, and a hyperglycemia induced by glucose application, upon glucose metabolism of the rat brain under ischemic and normoxic conditions are reported. in the ischemic brain, the initial glycolytic rate proved dependent on the glucose content being kept at various levels by glucose administration or hormone infusion prior to the onset of ischemia. The typical saturation kinetics revealed a maximal glucose conversion only from a definite initial content of brain glucose, being equivalent to a glucose level of approximately 13 mumole/ml in plasma, and appeared to depend on the presence of glucose in the cellular space. The early cessation of anaerobic lactate formation even with high glucose in the cellular space. The early cessation of anaerobic lactate formation even with high glucose depot in the brain tissue is referred to inhibition of glycolytic key enzymes by increasing tissue azidosis. The aerobic glucose conversion, as calculated from the Cglucose flux in amino acids associated with the citrate cycle was unaffected by the cerebral glucose content (hyperglycemia by hormone or glucose application). During glucose infusion the cerebral levels of NH3, total NH2 and glutamine rose; the Cglucose flux into aspartate and glutamine was increased and almost proportionally reduced in glutamate and gamma-aminobutyrate. These flux shifts are interpreted as a switching of C-chains from pyruvate owing to increased CO2 fixation, and as a biochemical correlate of an increased irritation level of the experimental animals.
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PMID:[Effect of increased plasma levels of glucose, adrenaline, and angiotensin upon glucose metabolism of totally ischemic and normally perfused rat brain]. 123 36

Cortical mouse astrocytes in culture were impaled with two-channel microelectrodes. These mouse astrocytes have the same responses to different K+ concentrations, ouabain, and glutamate as cultured rat astrocytes, with the exception that a large barium-sensitive K+ conductance clamps the membrane potential at the K+ equilibrium potential. Glycolytic and mitochondrial inhibitors have little effect on the mouse astrocytes. Total blockade of energy metabolism leads to an irreversible, calcium-dependent depolarization, but only if applied for longer than 45 min. Increasing the extracellular K+ concentration to 60 mM increases the intracellular K+ concentration by 43 mM and the bicarbonate concentration by 22 mM and leads to a concomitant fast swelling. Together with the 20 mM increase in Cl- concentration reported in the literature this is a good indication for a Boyle- and Conway-mediated K(+)-anion influx with water. This influx is accomplished by the depolarization-induced opening of Cl- channels as reported in the literature. In conclusion, ischemia-like conditions have little direct, immediate impact on astrocytes. In contrast, ischemia-induced release of substances from neurones, such as K+, produces an immediate and fast response.
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PMID:Coupling of metabolism and electrical activity in cortical astrocytes. 129 68

Carvedilol's potent antioxidant activity could explain its protective action in brain ischemia, but may not apply to glutamate-induced excitotoxicity in cultured cerebellar granule cells, since glutamate neurotoxicity was not associated with the formation of lipid peroxidative products. Rather, carvedilol diminished the N-methyl-D-aspartate (NMDA)/glycine-induced increase in intracellular calcium ([Ca2+]i), lowering [Ca2+]i by a maximum of 66 +/- 5% (n = 8) with a 50% inhibitory concentration of 0.8 microM. Prior addition of 5 microM dihydropyridines did not shift the dose-response of carvedilol, but did significantly lower the NMDA/glycine-stimulated response to 64% of untreated (n = 8, P = 0.014). Inclusion of 5 microM carvedilol before the additions of NMDA/glycine prevented 85% of the increase in [Ca2+]i. Furthermore, carvedilol displaced 3[H]MK-801 binding to rat brain cortical membranes with a Kd of 29.4 +/- 2.2 microM (n = 6) and no selectively for the glutamate or glycine binding sites. These data therefore suggest that, in addition to its antihypertensive and anti-lipid peroxidative functions, carvedilol has neuroprotective activity as a calcium channel blocker and as a non-competitive inhibitor at the NMDA receptor.
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PMID:Neuroprotective effects of carvedilol, a new antihypertensive, at the N-methyl-D-aspartate receptor. 130 May

In culture the protracted and abusive stimulation of glutamate (GLU) receptors results in neuronal death through a mechanism involving the persistent translocation of PKC and the destabilization of (Ca2+)i homeostasis [(Ca2+)i HD]. In contrast, intermittent GLU receptor use elicits a coordinated expression of immediate early genes (IEG) acting as nuclear third messenger. Brain ischemia also is known to result in the paroxysmal abusive stimulation of glutamate receptors. The glutamate receptive elements in turn degenerate largely as a function of their inability to control homeostatic Ca2+ due to the irreversible translocation of PKC. In the present study we employed an in vivo model of focal brain ischemia using the photosensitive dye, Rose bengal. With this model we sought to determine the neuroprotective actions of MK-801, a noncompetitive blocker of GLU at the NMDA-sensitive receptor and of the semisynthetic gangliosides LIGA 4 and LIGA 20 which in vitro have been demonstrated to block PKC translocation. Moreover, we sought to establish whether the persistent stimulation of ionotropic glutamate receptors would led to a change in ionotropic glutamate expression in the focal and perifocal area. Importantly, the perifocal area (i. e., the region surrounding the area of primary insult) is a region in which profound cellular reorganization occurs including neuronal death and glial proliferation and is a key region to target various neuroprotective drugs aimed at ameliorating the neurodegeneration following stroke. Receptor abuse dependent antagonists (RADA) drugs such as gangliosides selectively curtail the amplification steps that specifically differentiate signal transduction following physiological receptor use from that following pathological receptor abuse.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sequelae of biochemical events following photochemical injury of rat sensory-motor cortex: mechanism of ganglioside protection. 130 98

Recently, several lines of evidence have indicated the important roles of glial cells, especially astrocytes, in the regulation of neuronal functions. The neuron-glia interaction is one of the most important issues in neuroscience, including neuropharmacology. I reviewed the present status and perspectives on the physiologic and pathologic functions of astrocytes in relation to the roles of intracellular Cl-. Astrocytes have different types of Cl- transport systems, such as voltage-sensitive and ligand-gated channels; HCO3(-)-Cl- exchange; and Na+, K+, Cl- cotransport systems. Anion exchange and cotransport systems are responsible for intracellular pH regulation and astrocytic volume regulation, respectively. Especially, astrocytic volume regulation is physiologically important for reducing the concentrations of K+ and glutamate in the extracellular space by their uptake systems. Disturbance of astrocytic volume regulation is expressed as astrocytic swelling, which is usually observed in various brain pathologic states including ischemia. Experimentally, glutamate caused a typical swelling of astrocytes in culture by Cl- and Ca(++)-dependent processes. Glutamate-induced swelling is qualitatively different from reversible swelling induced by hypoosmotic medium. Recently, we found that Cl- is intracellular factor for modulating the receptor-adenylate cyclase system in brain slices. Similarly, the receptor- and forskolin-stimulated adenylate cyclase of astrocytes showed a clear Cl- dependence. This was functionally confirmed by astrocytic morphological transformation induced by the cyclic AMP system.
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PMID:[Regulation by chloride ion of astroglial cell functions and morphological transformation]. 131 34


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