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

This study examines the relationship between the concentration of extracellular glutamate released during 30 min of forebrain ischemia, and the subsequent development of ischemic neural necrosis, in the presence of three agents which act at distinct sites on the glutamatergic synapse: a presynaptic inhibitor of glutamate release (5-(2,3,5-trichlorophenyl)-2,4-diamino-pyramidine ethane sulphonate (BW1003C87)); a competitive NMDA receptor antagonist (cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS19755)); and a competitive AMPA receptor antagonist (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX)). Pretreatment with either BW1003C87 or NBQX markedly attenuated the peak concentration of extracellular glutamate and offered protection from post-ischemic neuronal necrosis in the CA1 hippocampus. In contrast, pretreatment with CGS19755 had no effect on extracellular glutamate release and did not protect CA1 hippocampal neurons from ischemic injury.
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PMID:BW1003C87 and NBQX but not CGS19755 reduce glutamate release and cerebral ischemic necrosis. 781 84

In a model of perinatal hypoxic-ischemic brain damage, we examined the neuroprotective efficacy of posttreatment with the NMDA receptor antagonist MK-801 and the AMPA receptor antagonist NBQX. Unilateral brain damage developed in 95% of rat pups subjected to hypoxia-ischemia with a 27.8 +/- 1.2% weight deficit of the damaged hemisphere. MK-801 in doses of 0.3 and 0.5 mg/kg i.p. reduced the brain damage by 61% (p < 0.001) and 43% (p < 0.001), respectively. A higher dose of MK-801 (0.75 mg/kg) did not offer neuroprotection. Treatment with NBQX (40 mg/kg) reduced the hemispheric lesion by 28% (p < 0.05). In conclusion, posttreatment with both NBQX and low doses of MK-801 reduced perinatal brain damage. The NMDA receptor antagonist offered stronger neuroprotection which is in agreement with a proposed NMDA receptor hyperactivity around postnatal day 7 in rats.
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PMID:Hypoxia-ischemia in the neonatal rat brain: histopathology after post-treatment with NMDA and non-NMDA receptor antagonists. 786 35

Several reports have indicated that the two glutamate receptor antagonists, dizocilpine (that binds to the phencyclidine recognition site of the NMDA (N-methyl-D-aspartate) receptor) and NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline, that binds to the AMPA (alpha-amino-3-hydroxy-5-methyl-isoxazole) receptor), protect neurons against damage caused by hypoxia, ischemia or excitotoxicity. We, therefore, used a combination of these drugs to achieve enhanced neuroprotection. Primary cultures of rat hippocampal neurons were challenged by glutamate intoxication. Both dizocilpine and NBQX produced dose-dependent increases in the percentage of viable neurons. Combined treatment with both glutamate receptor antagonists had an over-additive neuroprotective effect. Simultaneous administration of dizocilpine and NBQX also had a pronounced neuroprotective effect in vivo in mice subjected to focal cerebral ischemia and rats with global forebrain ischemia. This suggest that such a combination may have therapeutic relevance.
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PMID:Over-additive protective effect of dizocilpine and NBQX against neuronal damage. 791 Oct 83

We have used the laser-induced photochemical thrombosis model in adult rats to evaluate the significance of the non-N-methyl-D-aspartate (non-NMDA) subtype of glutamate receptors in situations of focal spinal cord ischemia. The animals were pretreated with the selective non-NMDA antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)-quinoxaline (NBQX) or, for comparison, the NMDA antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5-10-imine (MK-801). Neurological function was quantified using evaluations of motor score and inclined plane. The MK-801-treated rats had higher motor scores during the 3-week observation period while NBQX-treated rats only performed significantly better at 1 week. Both treatments caused significantly better performance in the inclined plane test. NBQX and MK-801 reduced the volume of necrosis by approximately 47% at 3 weeks postlesion. We conclude that blockade of both NMDA and non-NMDA subtypes of glutamate receptors reduces ischemic necrosis, possibly by preventing excessive stimulation of these receptors by released excitatory amino acids in the lesion area.
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PMID:NBQX, a competitive non-NMDA receptor antagonist, reduces degeneration due to focal spinal cord ischemia. 792 38

2,3-Dihydroxy-6-nitro-7-sulfamoylbenzo(F)-quinoxaline (NBQX), an alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist, has been reported to provide neuronal protection after global ischemia. The objectives of this study were to evaluate the neuroprotective effects of NBQX initiated after focal cortical ischemia and to validate a method for measuring functional outcome in this model. Male spontaneously hypertensive rats (SHRs) were exposed to various durations of transient or permanent tandem middle cerebral artery (MCA) occlusion. Studies compared motor performance using balance beam and prehensile-traction tests, calcium-calmodulin (Ca-CaM) binding by immunohistochemistry, and infarct volume between NBQX-treated animals [intravenous (i.v.) 5 mg/kg/h x 6 h or intraperitoneal (i.p.) 30 mg/kg q 30 min x 3 begun postischemia] and controls. All ischemic groups performed less well than sham-operated controls on the motor performance tasks in proportion to the severity of ischemia. No significant improvement in motor performance was noted in the NBQX-treated versus the control animals after 1 h or permanent MCA/CCA occlusion. Treatment with NBQX (i.v. or i.p. dosing) did not reduce Ca-CaM binding after 1 h of occlusion with 1 h of reperfusion or after 2 h of occlusion. Similarly, there was no reduction in infarct size between NBQX-treated and control animals after 24 h of permanent MCA/CCA occlusion (74.6 +/- 7.1 vs. 80.1 +/- 6.0 ml; ns) or after 1 h of occlusion with 23 h of reperfusion (55.1 +/- 4.4 vs. 47.4 +/- 6.2 ml; ns).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Motor performance, histologic damage, and calcium influx in rats treated with NBQX after focal ischemia. 811 22

Transient forebrain or global ischemia in rats induces selective and delayed damage of hippocampal CA1 neurons. In a previous study, we have shown that expression of GluR2, the kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit that governs Ca2+ permeability, is preferentially reduced in CA1 at a time point preceding neuronal degeneration. Postischemic administration of the selective AMPA receptor antagonist, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), protects CA1 neurons against delayed death. In this study we examined the effects of NBQX (at a neuroprotective dose) and of MK-801 (a selective NMDA receptor antagonist, not protective in this model) on kainate/AMPA receptor gene expression changes after global ischemia. We also examined the effects of transient forebrain ischemia on expression of the NMDA receptor subunit NMDAR1. In ischemic rats treated with saline, GluR2 and GluR3 mRNAs were markedly reduced in CA1 but were unchanged in CA3 or dentate gyrus. GluR1 and NMDAR1 mRNAs were not significantly changed in any region examined. Administration of NBQX or MK-801 did not alter the ischemia-induced changes in kainate/AMPA receptor gene expression. These findings suggest that NBQX affords neuroprotection by a direct blockade of kainate/AMPA receptors, rather than by a modification of GluR2 expression changes.
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PMID:NMDA and non-NMDA receptor gene expression following global brain ischemia in rats: effect of NMDA and non-NMDA receptor antagonists. 811 93

We have examined the significance of the serotonergic system in the pathophysiology of ischemic brain damage. Permanent occlusion of the middle cerebral artery (MCA) was performed in male NMRI mice. After 48 h, the animals received a transcardiac injection of carbon black. The area of ischemia was restricted to the neocortex and its size was determined planimetrically by means of an image analyzing system. In control experiments, the NMDA antagonist dizocilpine (MK-801), the AMPA/kainate antagonist NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)-quinoxaline) and the L-type calcium channel blocker nimodipine all produced a significant reduction in ischemic injury of the mouse neocortex. Interestingly, all of the 5-HT1A agonists tested (ipsapirone, CM 57493 [4-(3-trifluoromethylphenyl)-1-(2-cyanoethyl)-1,2,3,6-tetrahydropyridine ] and urapidil) were equally efficacious in reducing ischemic injury. On the other hand, the 5-HT2 antagonist naftidrofuryl failed to protect the brain tissue significantly against ischemic brain damage. Roxindole, a 5-HT1A agonist and 5-HT uptake inhibitor, was the most potent serotonergic compound tested. In order to examine the effects of 5-HT1A receptor activation in a different context, 10 min of forebrain ischemia was induced in male Wistar rats by a bilateral occlusion of the common carotid arteries combined with systemic hypotension. Administration of the 5-HT1A agonist CM 57493 reduced the neuronal damage within the ventral hippocampus and the entorhinal cortex as assessed histologically 7 days after ischemia. Finally, we found that 5-HT1A agonists are capable of reducing neuronal damage of cultured neocortical and hippocampal neurons subjected to a chemical hypoxia or glutamate in a dose dependent manner. These data suggest that 5-HT, released during ischemia, may have protective effects in the pathophysiology of ischemic brain damage through a direct action on neurons mediated via the inhibitory 5-HT1A receptor subtype. The results obtained from different in vivo and in vitro models indicate that 5-HT1A agonists are promising agents for the treatment of ischemic brain disorders.
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PMID:Effects of serotonergic drugs in experimental brain ischemia: evidence for a protective role of serotonin in cerebral ischemia. 811 77

The purpose of our study was to examine whether a significant interaction occurs between NMDA and non-NMDA receptor antagonists on respiratory function. For this purpose chloralose-anesthetized cats were used and respiratory minute volume (VE), tidal volume (Vt) respiratory rate (f), inspiratory and expiratory durations, and end tidal CO2 (FeCO2) were monitored. In some animals, phrenic nerve activity was also continuously recorded. In five spontaneously breathing animals, the NMDA receptor antagonist MK-801 was administered in a dose of 0.1 mg/kg i.v., and produced decreases in VE, Vt, f and increases in inspiratory duration and FeCO2. Using these five animals exhibiting respiratory effects from prior MK-801 dosing, we then administered the non-NMDA receptor antagonist NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline) i.v. in a dose of 3 mg/kg. This dose is too low to produce a neuroprotective effect in animal models of brain ischemia. In each of the five animals NBQX administration produced an immediate impairment of respiration, culminating in apneusis within 55 s after i.v. injection. In terms of phrenic nerve discharge, inspiratory duration was increased approximately 4-fold by MK-801, and with the addition of NBQX, continuous discharge of the phrenic nerve occurred. Finally, NBQX given i.v. to animals not pretreated with MK-801 had only a slight depressant effect on respiratory activity. These results obtained with co-administration of low doses of two drugs that block NMDA and non-NMDA receptors raise the spector that combined use of these agents to ameliorate disorders in neurological function may be extremely deleterious to respiratory function.
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PMID:Potentiation of MK-801-induced breathing impairment by 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline. 814 90

The new non-NMDA (N-methyl-D-aspartate) receptor antagonist NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline) has previously been shown to exert a neuroprotective effect in animal models of cerebral ischemia when administered in the post-ischemic phase. In this investigation the effect of NBQX on acidosis and energy recovery in early reperfusion after 10 min of transient forebrain ischemia with the 2-vessel occlusion model in the rat was studied with 31P NMR spectroscopy. In the intervention group the animals received a bolus dose of NBQX 30 mg.kg-1 i.v. at the start of reperfusion. 31P NMR spectroscopy was used to measure intracellular pH, ATP and phosphocreatine continuously in-vivo during, and after, the ischemic event. The recovery of high energy phosphates and pH was followed during 30 min of reperfusion. Pre-ischemic levels of phosphocreatine were reached after approximately 9-10 min in both groups. Although a slight improvement could be seen in the intervention group there was no significant difference in the rate of recovery between the two groups. ATP reached 90% of preischemic levels after about 8 min without significant difference between the two groups. With respect to the recovery of intracellular pH, no difference could be shown. Our results do not contradict previously published results, but suggest that the potential protective effect of NBQX is not mediated through improved recovery of energy metabolism in early reperfusion.
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PMID:NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline) did not affect recovery of high energy phosphates and pH in early reperfusion in a rat model of transient forebrain ischemia. Or: an in vivo 31P NMR spectroscopy study. 817 53

We have previously reported that transient spinal cord ischemia induced a behavioral hypersensitivity (allodynia) to innocuous cutaneous mechanical stimulation in rats. The spinal ischemia-induced allodynia was not relieved by morphine, but it was relieved by the gamma-aminobutyric acid (GABA)-B receptor agonist baclofen, indicating that the allodynia may be related to dysfunction of the spinal GABA-ergic inhibitory system. In the present study we report that systemic application of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), an antagonist of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor for excitatory amino acids, dose-dependently relieved allodynia after spinal cord ischemia. The analgesic effect of NBQX at a low dose (7.5 mg/kg) was not accompanied by motor deficits or sedation. On the other hand, the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) only partially alleviated allodynia, even at doses that produced severe motor deficits. It is suggested that the abnormal, possibly painful, sensations elicited by innocuous mechanical stimulation observed after spinal cord ischemia may be mediated by excitatory amino acids, acting mainly on the AMPA receptor. Antagonists of excitatory amino acid receptors, especially at the AMPA site, may be effective in treating pain conditions where input from low threshold afferents triggers painful sensations.
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PMID:Systemic excitatory amino acid receptor antagonists of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and of the N-methyl-D-aspartate (NMDA) receptor relieve mechanical hypersensitivity after transient spinal cord ischemia in rats. 822 41


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