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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Na(+) influx has been implicated to play an important role in the mechanisms of neuronal cell damage under ischemia as well as in neurodegenerative disorders. Thus far, however, the effects of Na(+) influx on astrocytic damage have not been studied extensively. In the present study, we have examined the effects of Na(+) influx induced by veratridine (Na(+) channel opener), monensin (Na(+) ionophore), and glutamate (co-transportation with Na(+)) on rat cultured astroglial damage. Cells were incubated with bicarbonate buffer with 25 mM glucose containing either 100 microM veratridine, 10 microM monensin, or 1 mM glutamate with or without 1 mM ouabain for 20 h. Cellular damage was evaluated quantitatively by lactate dehydrogenase (LDH) release or 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) reduction. Veratridine, monensin, or glutamate alone did not induce significant astroglial damage. Veratridine and monensin co-incubated with ouabain, which inhibits active extrusion of Na(+) by Na(+),K(+)-ATPase, thereby enhances intracellular Na(+) accumulation, caused significant cell death (P<0. 001, approximately 50% cell damage), whereas glutamate did not. Na(+)-free solution substituted by choline (impermeable cation) attenuated cell damage induced by veratridine and monensin markedly, while Li(+) substitution (permeable cation) rather exacerbated. Nifedipine (100 microM), a blocker of L-type Ca(2+) channel, reduced veratridine-induced glial damage by 50%. Neither bepridil nor benzamil, a blocker of Na(+)-Ca(2+) exchanger, had any protection. Cyclosporin A (1 or 10 microM), an inhibitor of mitochondrial permeability transition or 10 microM N-benzyloxycarbonyl-Val-Ala-Asp-(O-methyl)fluoromethyl ketone (zVAD-fmk), which inhibits a broad range of caspases, did not show protective effects.
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PMID:Astroglial cell death induced by excessive influx of sodium ions. 1108 May 18

The role of the L-arginine/nitric oxide (NO) pathway in myocardial ischaemic/reperfusion injury remains controversial in experimental animal models. The aim of the present studies was to investigate the role of this pathway in the human myocardium. Myocardial specimens from right atrial appendages of patients undergoing elective coronary bypass graft surgery were incubated in crystalloid buffer at 37 degrees C and subjected to 120 min of simulated ischaemia followed by 120 min of reoxygenation. Tested drugs were added 15 min before ischaemia, and maintained during ischaemia and throughout reoxygenation. Ischaemia resulted in severe myocardial damage, as assessed by the leakage of lactate dehydrogenase (LDH) into the incubation medium and by the capacity of the tissue to reduce 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to formazan product. L-Arginine (10 mM), a precursor of NO, significantly decreased LDH leakage (from 9.0+/-0.6 to 5.3+/-0.3 units/g wet wt; P<0.05), but had no effect on MTT reduction or oxygen consumption. D-Arginine (10 mM), N(G)-nitro-L-arginine methyl ester (L-NAME; 0.5 mM), an NO synthase inhibitor, and S-nitroso-N-acetylpenicillamine (at 1, 100, 500 and 1000 microM), an NO donor, had no significant effects on the measured indices, and L-NAME did not reverse the protection afforded by L-arginine against LDH leakage. In addition, the formation of nitrotyrosine was not influenced by ischaemia/reoxygenation alone or by the agents investigated. In conclusion, these data suggest that L-arginine affords modest protection against ischaemic/reoxygenation injury of the human myocardium, an action that is NO-independent, and that NO metabolism does not play a significant role in this model.
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PMID:Role of the L-arginine/nitric oxide pathway in ischaemic/reoxygenation injury of the human myocardium. 1109 92

Ebselen is a selenium compound that have glutathione peroxidase-like activity which is neuroprotective in acute stroke ischemia. The efficacy of ebselen to prevent excitotoxicity provoked by glutamate in cerebellar granule neurons was investigated at various time points and concentrations. Simultaneous addition of ebselen with glutamate decreased neuronal death and was completely reversed by 3 microM of ebselen (3 (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and propidium iodide assays). However, when 1 microM of ebselen was added with glutamate and remained in the culture medium until 24 or 48 h, the neuronal survival increased to the control. The mechanism proposed for neuroprotection was the ability of ebselen to prevent lipoperoxidation provoked by glutamate. The present findings propose to amplify the use of ebselen in others neurodegenerative disorders involving glutamatergic system.
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PMID:Ebselen prevents excitotoxicity provoked by glutamate in rat cerebellar granule neurons. 1116 74

Pancreatic islet transplantation in humans is a promising alternative for substitutive insulin therapy of IDDM (Insulin Dependent Diabetes Mellitus). Storage of harvested organs is a one of the most important factors, which influence efficacy of islet isolation process. In this sense, appropriate pancreas storage is the main point the successful pancreatic islet isolation. The purpose of the present study was to find out whether lidocaine, a well known membrane stabilizer and PLA2 (phospholipase A2) inhibitor could be applied in pancreas preservation for protection of endo- and exocrine pancreatic tissue from cells damage which occurs during and after storage. For this purpose, the effects of lidocaine on 1) viability and 2) endocrine function of pancreatic islets, isolated from pancreases exposed to cold ischemia, were investigated in this study. Our study showed hat lidocaine, injected intraductally before pancreas harvesting, improves efficacy of islet isolation. We found that the yields of islets in the groups treated with lidocaine were significantly higher when compared with controls. Glucose challenge test performed on these islets indicated that after the treatment with lidocaine, islets were more sensitive to glucose stimulation when compared with control islets, although the metabolic activity estimated by MTT test was comparable in both groups. In summary, donor pretreatment with lidocaine seems to be the safe method of protection of preserved pancreases from cell damage, caused by membranes destruction during cold ischemia.
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PMID:Lidocaine as a protective agent during pancreas cold ischemia. 1124 52

Increased levels of extracellular excitatory amino acids and failure of energy metabolism are two conditions associated with brain ischemia. In the present study we have combined the simultaneous inhibition of glutamate uptake and mitochondrial electron transport chain to simulate neuronal damage associated with brain ischemia. Results show that cerebellar granule neurons are not vulnerable to transient glutamate uptake inhibition by L-trans-pyrrolidine-2,4-dicarboxylate (PDC) despite the increase in the extracellular concentration of glutamate, unless they are simultaneously exposed to the mitochondrial toxins 3-nitropropionic acid (3-NP) or sodium azide. Cell damage was assessed by light microscopy observation, by reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and by the fluorescent markers for live and dead cells, calcein and ethidium homodimer, respectively. The protective effect of alternative energy substrates, such as pyruvate, acetoacetate, and beta-hydroxybutyrate against PDC-induced neuronal death during 3-NP exposure was studied and compared to the effects of the antioxidant vitamin E, the spin trapper alpha-phenyl-N-tert-butylnitrone (PBN), voltage-dependent calcium channel antagonists, and glutamate receptor antagonists. Results show that neuronal damage can be efficiently prevented in the presence of pyruvate and the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801, whereas the non-NMDA receptor antagonist NBQX, acetoacetate, vitamin E, and PBN showed partial protection. In contrast, beta-hydroxybutyrate and voltage-dependent calcium channels blockers did not show any protective effect at the concentrations tested.
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PMID:Strategies for neuroprotection against L-trans-2,4-pyrrolidine dicarboxylate-induced neuronal damage during energy impairment in vitro. 1134 Jun 49

Taurine has been shown to be an effective scavenger of hypochlorous acid (HOCl). The role of HOCl is well established in tissue damage associated with reperfusion injury mediated by neutrophils. The role of HOCl in CNS injury and inflammatory reactions has not been well established. Myeloperoxidase activity is present in the CNS and it has been associated with ischemic injury. The aim of the present study was to determine the cytotoxicity of HOCl in a neuronal cell line (PC12) and the ability of taurine to prevent or reverse neurotoxicity. PC12 cells were grown in 96 well plates at a plating density of approximately 100,000 cells per well. HOCl was made up fresh from NaOCl for each experiment and the concentration verified spectrophotometrically. PC12 cells were exposed to HOCl for 1 hour in phosphate-buffered saline. Taurine was added at the time of HOCl treatment and in some experiments a post-treatment with taurine was performed by adding 1 or 10 mM taurine to the culture media (RPMI 1640). The cells were allowed 24 hours to recover and viability was determined using a tetrazolium-based (MTT) assay. The first series of experiments evaluated the toxicity of HOCl and the efficacy of taurine to protect PC12 cells. HOCl at 50 microM reduced PC12 cell viability by 50% and 150 microM reduced viability to <25% of control levels. Taurine (0.5-20 mM) was tested for cytoprotection against 150 microM HOCl and PC12 cells treated with 0.5 mM taurine exhibited only a 20% reduction in viability compared to untreated controls. Taurine concentrations of 1 mM or higher provided nearly 100% protection against HOCl. A second study was performed comparing taurine to beta-alanine, glutathione and isethionic acid. HOCl (100 microM) reduced viability to 25 +/- 1% of controls and taurine, beta-alanine and glutathione at 1 mM provided nearly complete protection. In contrast, isethionic acid, which lacks an amino group, failed to provide protection. Taurine (1 or 10 mM) added after 50 microM HOCl treatment did not provide any protection and PC12 cell viability was reduced to <39% of controls. In contrast, if taurine (50 microM) was present during the HOCl treatment and 1 mM taurine was added after the treatment, PC12 cell viability was 80 +/- 5% of controls. A combination of 250 microM taurine during the HOCl treatment and 1 mM taurine post-treatment produced 100% protection. These results clearly show that taurine is an efficient scavenger of HOCl and can prevent neuronal damage caused by HOCl. Since myeloperoxidase expression in the CNS is increased by ischemia, one function of taurine released during an ischemic event may be to scavenge HOCl and provide neuroprotection.
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PMID:Cytoprotective effect of taurine against hypochlorous acid toxicity to PC12 cells. 1178 41

O, O-acetyldaurisoline(Adau) is a derivative of daurisoline (Dau). In cultured PC12 cells, Adau was found to inhibit K+, Bay K8644 and norepinephrine induced intracellular free calcium concentration increase. Adau was also shown to protect PC12 cells from hypoxia-reoxygenation injury with EC50 of 64.3 +/- 12.5 mumol.L-1 by MTT assay. Adau (2.5, 5 and 10 mg.kg-1, i.v.) administrated 30 min before ischemia in bilateral carotid artery occlusion and four-vessel occlusion rats, attenuated the increase of lipid peroxide content and the decrease of SOD activity. These results show that Adau have significant protective effects against ischemic injury.
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PMID:[The anti-ischemic effect of O, O-acetyldaurisoline]. 1193 60

1. Guanosine-5'-monophosphate (GMP) was evaluated as a neuroprotective agent against the damage observed in rat hippocampal slices submitted to an in vitro model of ischemia with or without the presence of the ionotropic glutamate receptor agonist, Kainic acid (KA). 2. Cellular injury was evaluated by MTT reduction, lactate dehydrogenase(LDH) release assay, and measurement of intracellular ATP levels. 3. In slices submitted to ischemic conditions, 1 mM GMP partially prevented the decrease in cell viability induced by glucose and oxygen deprivation and the addition of KA. 4. KA or N-methyl-D-aspartate (NMDA) receptor antagonists, gamma-D-glutamylamino-methylsulfonate (GAMS) or (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801, 20 microM) also prevented toxicity in hippocampal slices under ischemic conditions, respectively. 5. The association of GMP with GAMS or MK-801 did not induce additional protection than that observed with GMP or that classical glutamate receptor antagonists alone. 6. GMP, probably by interacting with ionotropic glutamate receptors, attenuated the damage caused by glucose and oxygen deprivation in hippocampal slices. This neuroprotective action of GMP in this model of excitotoxicity is of outstanding interest in the search for effective therapies against ischemic injury.
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PMID:Neuroprotective effect of GMP in hippocampal slices submitted to an in vitro model of ischemia. 1246 74

To study the effect of extracellular acidosis on apoptosis and necrosis during ischemia and reoxygenation, we exposed human post-mitotic NT2-N neurones to oxygen and glucose deprivation (OGD) followed by reoxygenation. In some experiments, pH of the cell medium was lowered to 5.9 during either OGD or reoxygenation or both. Staurosporine, used as a positive control for apoptosis, caused Poly(ADP-ribose)-polymerase (PARP) cleavage and nuclear fragmentation, but no PARP cleavage and little fragmentation were seen after OGD. Low molecular weight DNA fragments were found after staurosporine treatment, but not after OGD. No protective effect of caspase inhibitors was seen after 3 h of OGD and 21 h of reoxygenation, but after 45 h of reoxygenation caspase inhibition induced a modest improvement in 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) cleavage. While acidosis during OGD accompanied by neutral medium during reoxygenation protected the neurones (MTT: 228 +/- 117% of neutral medium, p < 0.001), acidosis during reoxygenation only was detrimental (MTT: 38 +/- 25%, p < 0.01). We conclude that apoptotic mechanisms play a minor role after OGD in NT2-N neurones. The effect of acidosis on neuronal survival depends on the timing of acidosis, as acidosis was protective during OGD and detrimental during reoxygenation.
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PMID:Acidosis has opposite effects on neuronal survival during hypoxia and reoxygenation. 1260 26

As a potent free radical scavenger and antioxidant, melatonin protects brain tissue against ischemia-reperfusion injury, partly via suppression of ischemia-induced production of nitric oxide, when given before ischemia-reperfusion or within 2 hr of onset of ischemia. In this study, we examined the neuroprotective effect of melatonin in an in vitro model of ischemia. Primary cultured astrocytes were subjected to 4 or 8 hr of oxygen-glucose deprivation (OGD), and cultured SHSY5Y human neuronal cells were exposed to 1 hr of OGD. Melatonin was added to the medium at the commencement of OGD to achieve different final concentrations, and cell death was quantified using the measurement of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) at 24 hr after reversion of OGD. Treatment with melatonin did not affect the astrocytic cell death following 4 or 8 hr of OGD. The relative MTT values of the neuronal cells were (as mean +/- S.E.M.) 59.1 +/- 2.4% in the vehicle-treated OGD group and 80.1 +/- 2.7%, 82.5 +/- 2.9%, 74.1 +/- 2.3%, 64.2 +/- 2.3%, 62.7 +/- 2.8%, and 61.0 +/- 3.9% in the OGD groups treated with melatonin at 10(-3), 10(-4), 10(-5), 10(-6), 10(-7), and 10(-8) m, respectively. Reduction in cell death was significant following treatment with melatonin at 10(-3), 10(-4), or 10(-5) m. Reverse transcription-polymerase chain reaction showed that human mt1 and MT2 membrane receptors were not expressed in the cultured neuronal cells. Our results show that melatonin co-treatment protects cultured neuronal cells but not astrocytes against OGD-induced cell death in a dose-dependent manner and that the neuroprotection is independent of its known membrane receptors.
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PMID:Melatonin protects SHSY5Y neuronal cells but not cultured astrocytes from ischemia due to oxygen and glucose deprivation. 1261 79


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